Sloth Metabolism

"Their metabolism is so slow that they may take a half a minute to move a leg a few inches. Their digestive system is so slow that they need only defecate about once a week. They even sneeze slowly."
http://www.zootorah.com/

Some people still don’t get it. When I say “it” I mean the centrality of a high cellular metabolic rate in disease prevention, body composition, and overcoming many common health problems big and small as discussed in THIS FREE EBOOK.

Big names in “alternative nutrition” like Mark Sisson and Joel Fuhrman, who make relatively sound general dietary prescriptions (eat nutritious foods at the exclusion of most junk), have both negated the importance of metabolism – and even believe it’s good to have a low metabolism. Everyone else shrugs it off, typically because they have convinced themselves that they are the healthiest person on earth, and when they see that their body temperature is low they say either:

a) Body temperature must not matter
b) It might even be good to have a low body temperature
c) Matt Stone is a douche
d) All of the above

It’s time for a simpler example to establish the real differences between high cellular metabolic rate and low cellular metabolic rate. After all, that’s all that I’m really concerned with. If you are talking about total calories burned, the best way to “raise your metabolism” is to get as muscular and fat as you can possibly get, like Sumo wrestlers that have the highest metabolic rates of any humans. But I doubt that’s what most people are after. Most people want to be lean, energetic, not have to spend all day sleeping, and otherwise not live like a sloth - or look like a Sumo.

Speaking of sloths, isn’t it cute that the mammal with the lowest metabolic rate (other than hibernating animals which are so lifeless as to be almost indistinguishable from a corpse), is the animal most notorious for having next to zero vitality, vigor, speed, and strength?

The sloth has the lowest metabolic rate of any mammal – and the body temperature to show for it at about 93 degrees F supposedly. Of course, in the modern world we blame our sedentary lifestyles on laziness or modern convenience. Well, my eight year-old niece has access to plenty of couches and televisions and computers, but after spending a week with her I fully understand why she eats 2,500 + calories per day and literally has a little visible (slightly) 6-pack. That kid cannot sit still, and can be hot even when sopping wet in cool temperatures. That’s what happens when you eat ice cream in quantities equal to the size of your head on a daily basis.

Anyway, tail wagging the dog people, tail wagging the dog. I just wanted to say that. I’m not fully sure what it means.

And speaking of tails, does anyone know if sloths have them? I’m not sure. I am sure that I googled “sloth metabolism” (who hasn’t really?) and found a nice article featuring factoids such as sloths having a body temperature of 93 degrees F, a transit time of up to 30 days, they sleep 14-16 hours per day, have very little muscle mass, strength, energy, or speed – and otherwise spend most of their time conserving energy just like a human in hibernation/famine/starvation mode does.

So when I paint a portrait of certain things being quite simple – “Oh, raise your metabolism and your digestion will get better and you’ll probably eradicate constipation for life by the “turd” week of following THIS GENERAL PROGRAM,” in many cases it really is precisely that simple. Not all of course, but a high percentage of cases.

Take sloth digestion for example. They eat, and the food takes 30 days to get out the other end because they digest it so slowly. In a reduced metabolic state, the bowel transit time slows down to extract as many calories from the food as possible. It stays in the gut fermenting and putrefying, causing gas and irritation and inflammation and toxin absorption, bacteria proliferate (in humans this might cause bacterial overgrowth of the small intestine, or SIBO – in turn causing fructose malabsorption, hypoglycemia, yada yada), stool moisture decreases causing stool hardening typical of the constipated, this causes gas and more irritation – potentially wearing away at the intestinal wall and causing serious problems and who knows what else, straining to expel stools can cause hemorrhoids, fissures, diverticulosis, and varicose veins, and on and on and on and on. It is all interconnected to metabolic rate.

The only question one needs to ask is what kind of health experience are you looking for? Do you want to have lots of energy? Strength, endurance, and vitality? A decreased need for sleep and rest or an increased need for sleep and rest?

To me it seems painfully obvious. The modern diet, lifestyle, and other factors seemed to have combined somehow to cause an epidemic of slothlike metabolism. Yes, a sloth metabolism epidemic. That’s what we’re looking at in the world today. This is why a nurse I spoke with recently said that she saw a body temperature of 98.6 degrees F or above in an average of ZERO out of 150 daily readings. Yet, although this body temperature is now an extreme rarity, at one point this was so normal that it helped to establish 98.6 degrees F as normal. We ain’t what we used to be.

Fixing it requires a well-strategized approach in my view. Just eating some nutritious food and not trying to break any records running marathons is probably helpful for a lot of people, but getting out of sloth metabolism and into a state in which your body’s cells are producing energy at a high enough level for it to translate into massive increases in overall vitality probably takes more than that. 

If you’d like to know how a low metabolism translates to poor fertility and low sex drive I encourage you to research the bear with the lowest metabolic rate. You know, it’s the one that is about to go extinct because of the horrible and biologically-inappropriate diet it evolved to eat during the Paleolithic era (almost entirely vegan, 99% bamboo). It’s the one that zookeepers can’t figure out how to get to have sex, much less reproduce – the one they are now resorting to showing pornographic images to in hopes of getting them in the mood.

The biggest question is, how appropriate is a Baby Ruth candy bar for a Sloth?  Will it help, or will it make your friends insist that you do the truffle shuffle before entering their home?  I would think potatoes and coconut oil would be more helpful, but I'll be damned if I'm not enjoying the heck out of some juice and key lime pie right now.  I don't want to eat foods with a low calorie density like sloths, panda bears, and koalas - regardless of what that might do for my huggability.

Of course I'm terribly torn.  On the one hand high-calorie density foods with a pornographic nature (pornographic foods Sally Fallon calls them - a great term) seem to short-circuit the homeostatic weight regulation mechanism, causing those sensitive to "conditioned hypereating" to eat more without a rise in metabolism.  Yet, the pornographic foods (within reason - low-PUFA sans chemical flavor enhancers), make me strong like bull.  We'll save that for a future masturdebate I suppose.      

Sleep and Cognition in Late-Life Depression

Depression commonly occurs with subjective as well as objective impairment in sleep and cognition.   However, few studies have examined the interaction between sleep impairment, cognition and depression in elderly cohorts.   Sleep disturbances predict increased risk for new onset depression and recurrence of depression in those with previous episodes.  Impaired sleep appears to reduce memory function and possibly reduce neurogenesis. 

Naismith and colleagues recently examined the correlations between sleep parameter and cognition in a group of 44 subjects with a lifetime history of depression (minimum age >45 years, mean 63 years) and a group of similarly aged adults without depression.  Neuropsychological testing in this study focused on domains felt to be impaired in mood disorders including: 1.) processing speed, 2.) attention, 3.)visual memory, 4.) verbal memory, 5.) language-as tested by counting number of animal names produced in one minute and 6.) executive function-planning, problem solving and response inhibition.

Sleep function was measured using actigraphy and sleep diaries.  Actigraphy typically involves using a wrist watch type device that measures movement during the night and provides an estimate of key sleep parameters including: 1.) total rest interval 2.) sleep latency—time from going to bed to falling asleep (in minutes), 3.) wake after sleep onset (WASO), 4.) arousals—number of periods during night where activity indicated being awake and 5.) sleep efficiency—the percent time asleep during the night

Elderly subjects with a history of depression (current depression ratings suggest a relatively mild depression cohort at time of study) showed increased WASO and decreased sleep efficiency (two highly correlated sleep variables).   WASO and sleep efficiency variables correlated with reduced cognitive function particularly in the domains of attention, memory (semantic and visual) and executive function.  Of note, late onset of depression tended to be associated with poorer sleep quality than earlier age of onset.  The authors controlled for depression severity in this study so the findings appear outside of this influence.

The authors suggest greater cognitive impairment in late onset depression may relate to white matter changes due to cerebrovascular disease.   White matter changes in frontal cortex-subcortical circuits have been associated with reduction in psychomotor speed and executive function.

The authors also note this study is unable to identify the sequencing and causal pathway for these relationships.  If impaired sleep directly impairs cognition, early identification of sleep abnormalities and treatment may limit associated cognitive impairment.  Sleep apnea also needs to be considered in this population, although the authors found no association between measures of sleep apnea and cognitive impairment.

The take home message from this study is that sleep impairment (poor efficiency) may be a marker for depression and cognitive impairment in those over 50.  Clinicians caring for the older adult, should carefully assess the health of the sleep of their patients and keep the sleep, cognition and depression triad in mind.  Sleep complaints in older adults need thorough assessment and should not be dismissed simply as age-related physiological in nature. 

Photo of Tiger Woods putting during practice for 2010 PGA championship courtesy of Yates Photography.

Naismith SL, Rogers NL, Lewis SJ, Terpening Z, Ip T, Diamond K, Norrie L, & Hickie IB (2011). Sleep disturbance relates to neuropsychological functioning in late-life depression. Journal of affective disorders PMID: 21435728

Raw Jicama Chili Fries

I absolutely love these delicious Jicama Chili Fries. Jicama (pronounced \ˈhē-kə-mə\ is a a pale brown turnip with a crisp sweet taste. It is the tuberous root of a tropical American vine (Pachyrhizus erosus) of the legume family that is eaten raw or cooked.  The Jicama originated in Mexico. You can find jicamas in most stores. I only used one jicama to produce this big bowl of fries!  Jicama health benefits are numerous! It is low in calories and an excellent source of fiber, potassium, iron, calcium, and vitamins C and E. In fact, 1 cup of jicama contains nearly 6 grams of fiber. Jicama helps keep your cholesterol levels under control and may help protect against heart disease. Eating jicama also helps boost your immune system, promote healthy bones, and protect you against colds and flu - all great reasons for enjoying jicama.  You will love these!

Raw Jicama Chili Fries
Printable Recipe

1 large jicama
1 tsp. extra virgin olive oil
1 tsp. chili powder
2 tsp. nutritional yeast
1/4 tsp. sea salt

1.)  Peel and slice jicama into french fry shapes.  Coat well with 1 tsp. olive oil.  Add chili powder, nutritional yeast and salt.  Mix well and serve.

Suicide Tops Death List for Meth Heads

Methamphetamine Chemical Structure

Methamphetamine dependence can lead to an early death.  The magnitude and mechanism of this effect is not well understood.  One way to better understand effects of drug abuse/dependence on mortality is the prospective outcome study.  These types of studies tend to be costly and may require many years to yield research results.   That’s why there are not many published studies to answer the question of this post.

A recent study from Taiwan provides some valuable insight into this issue.  This study followed a cohort of 1254 individuals with a history of methamphetamine abuse and a psychiatric admission for treatment between 1990 and 2007.  National death records were queried and the methamphetamine abuse cases were compared to an age- and gender- matched control group.  One hundred thirty methamphetamine users died during follow up with the following leading categories of death:  

• Suicide n=42 (32.3%)
• Accidents n=26 (20.0%)
• Undetermined unnatural deaths n=14 (10.8%)
• Cardiovascular disease n=13 (10.0%)
• Undetermined natural deaths n=9 (6.9%)
• Liver disease n=6 (4.6%)

In this Taiwanese sample, methamphetamine abuse carried an overall six fold increase in mortality.  Unnatural deaths (suicides, accidents, homicides, undetermined natural deaths) were particularly elevated.  Male amphetamine abusers had about a 10-fold increase in unnatural deaths while female methamphetamine abusers had a remarkable 26-fold increase in unnatural death during follow up.

Being married appeared to reduce the risk of death from unnatural and natural causes in this cohort.  Use of other substances in addition to methamphetamine increased risk of death.

I would suspect that in the United States, homicide would be a greater contributor to mortality in those with a history of methamphetamine dependence.  Overall homicide rates in Taiwan are much lower than in the United States and may reduce risk for this type of unnatural death.

Interestingly, about two thirds of the cohort had exhibited methamphetamine psychosis-a psychiatric complication of methamphetamine use.  Those with a history of this type of psychosis were no more likely to die than those without a history of the psychosis.

One problem with this type of study is difficulty assessing the specific effect of methamphetamine from other potential confounding factors.  For example, methamphetamine use is higher in smokers than smokers and so some increased mortality risk could be related to effects of smoking.  Methamphetamine dependence is more prevalent in a variety of mental disorders linked to increased suicide.

Nevertheless, this study shows the magnitude and type of mortality risk linked to methamphetamine dependence.  Public health interventions that reduce the prevalence of methamphetamine dependence would like reduce the excess mortality associated with this drug.

Wikipedia Commons chemical structure of methamphetamine image authored by Harbin.

Kuo CJ, Liao YT, Chen WJ, Tsai SY, Lin SK, & Chen CC (2010). Causes of death of patients with methamphetamine dependence: A record-linkage study. Drug and alcohol review PMID: 21355920

The Limitations of Interval Training

I’ve heard a few people make remarks like, “Matt is recommending interval training.” I’m not actually. Interval training is just as retarded as many other forms of exercise, and this is why...

If you read stuff like Lyle McDonald, you’ll notice that no such magic status is given to interval training over other forms of exercise. If there are any advantages to it, those advantages are short-lived, expiring after 6-8 weeks or so. I would agree with this wholeheartedly.

Any form of exercise that you do that contains no element of progression will cease to continually give you results. Bodybuilders seem to understand this general principle of exercise and adaptation better than anyone else. To continually gain strength and muscle size, the exercise has to get harder and harder over months and years.

But with interval training as it is typically performed, the exercise doesn’t get harder and harder. It gets easier and easier, putting the brakes on adaptive hormonal changes that increase your fitness levels, partition the food you eat into muscle cells, and trigger spontaneous fat loss. That’s because, when you do the same thing over and over again, it gets easier and progressively LESS challenging. In a short period of time, usually just a couple of months or less, the body has fully adapted to the training and no longer needs to keep changing to meet the demand you are placing on it.

That’s one of the big problems with traditional interval training. When you go for a set number of seconds and then recover for a set number of seconds – and those time periods remain constant, the exercise becomes increasingly less challenging and therefore less effective over time.

This is what makes Al Sears’s PACE program innovative and effective beyond just the initial phase. Still, I find that the PACE program is difficult to grasp. Even Dr. Mercola reported in his Peak 8 interval training video that he didn’t really understand PACE or ever figure out how to implement the idea of it.



Instead, Mercola went the traditional interval training route and had fantastic results in the short-term, but I think he will find that these results taper off and then stall completely over time. In one of the videos he even mentions that his heart rate used to get a lot higher when he was doing the intervals. This is of course a sign that his body has adapted to the intervals, and without new challenges and new hurdles that push his body to its limits, he won’t continue to get the results.

This is what got me sort of re-branding this concept in a side project I’ve been working on and have shared with a handful of people. The concept that needed to be hammered home was that the effort that you give must be one of maximum exertion.

It’s this maximum effort, taking the lungs and heart to the limits of their working potential and stimulating them to get better in order to be better prepared for the next challenge that continues to produce results. When you “push it to the limit” as demonstrated by the Turkish Doug Graham in this training video, you can expect a lot more from doing short bursts of hard exercise than you can from standard interval training.



Plus, going to your own personal threshold is precisely that – very personal. Set interval times are anything but personal, offering up a one-size fits all to a broad array of people of all shapes, sizes, ages, and fitness levels. For some, doing a 30 second sprint on a bike might necessitate 7 minutes of recovery before attempting another round. For others just walking on a flat surface for a minute may require 7 minutes of recovery. For a professional athlete, a 30 second sprint on a bike might not even get them totally winded, and a recovery period of 90 seconds may be way too long to challenge their capacity for exertion and recovery.

But if you ditch the set times and go to your threshold with a maximum effort – reaching that threshold in as little time as possible (close to sprint intensity), then you have “interval” training that is custom fit to your fitness level at that very moment – and it always progresses along with you, as hard each time you do it as it was the first time when you were totally out of shape. Frequently switching to new exercises helps prevent adaptation and keeps you growing even more.

Of course it’s this continual progression that creates continual adaptation. And the metabolic adaptations to exercise are what have the possibility to yield fat loss and health improvements without willpower, calorie restriction or even thinking about your diet, or rebound weight gain. In fact, take a month off from this type of exercise and you’ll likely find yourself getting even leaner – not gaining 10 pounds with the snap of your fingers as happens when you stop doing “cardio.”

So no, I’m not recommending interval training. I’m saying that if you are trying to lose fat and wondering if exercise can assist you, the type to do is one that causes metabolic adaptations that favor fat loss. We’re not talking burning calories or glycogen depletion or mechanically burning fat by being in some “fat-burning zone.” That stuff is beyond useless long-term in my experience. Instead it’s about providing a stimulus to the body that makes it view fat storage as a liability – activating all its “programs” to prevent body fat from accumulating. Not everyone has a dramatic response to this type of training, but many do. Very dramatic. And personally, I think the health and fitness benefits of expanding lung and heart capacity make this form of exercise worth doing even if it doesn’t do squat for your body composition.

In short…

Metabolic Adaptation Exercise is done by performing a burst of maximum intensity exertion.

MAX effort + Metabolic Adaption Xercise (MAX) = MAXercise

Yeah, I know it’s cheesier than the macaroni and cheese I’ll be eating for dinner, but it has meaning and that meaning is important. I think the concept can be loosely applied to just about any type of exercise. And what’s most remarkable about it is how much some people’s fitness, energy levels, and body composition can change with as little as 2-3 minutes of total exertion time each week.

Key Elements in Differentiating ADHD and Autism

ADHD and autism spectrum share several clinical features making the differential diagnosis challenging.  Both disorders show impairment in executive control (planning and carrying out complex cognitive tasks) and problems with social function.  Methods to distinguish the two are needed to aid clinicians and parents in obtaining the correct diagnosis and beginning appropriate treatment.

Buhler  and colleagues have recently published a study that examines the psychological qualities of inhibitory control and theory of mind as differential qualities.  The key elements of the design of their study include:

Subjects: Three groups--one group diagnosed with autism spectrum disorder from a German special ASD clinic.  A second group of children diagnosed with ADHD.  A third group consisted of children with both a ASD diagnosis and an ADHD diagnosis.

Neuropsychological testing included a test of attention performance (Test Battery for Attention Performance-TAP) and theory of mind (Facial Emotion Matching-FEM) and the Social Attribution Task (SAT).

Statisitical Analysis: Discriminant function analysis was completed to determine the combination of testing scores that separated the diagnostic groups.

The authors found that combining commission errors from the TAP and the eye-mistakes from the FEM provided moderate classification among younger children (positive predictive value for ASD 65% and for ADHD 79%).  The older children (over 10 years old) were discriminated by a combination of commission errors on the TAP and the reaction time on the FEM.  The positive predictive values were somewhat lower for the older children--63% for ASD and 51% for the ADHD group.

The authors concluded: "..a specification of the existing categories of ASH and ADHD interms of the parameter inhibitory control and by adopting a developmental prospectives with theory of mind, allows to differentiate between the disorders."

Combined neuropsychological testing and brain imaging may provide a better research strategy to distinguish between these two childhood onset disorders. 

Photo of Juno Beach Florida Sunrise Courtesy of Yates Photography

Bühler E, Bachmann C, Goyert H, Heinzel-Gutenbrunner M, & Kamp-Becker I (2011). Differential Diagnosis of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder by Means of Inhibitory Control and 'Theory of Mind' Journal of autism and developmental disorders PMID: 21373957

Man as Social Animal: TED talk of David Brooks

David Brooks has been a political journalist for the New York Times for many years.  Recently he has developed an interest in cognitive neuroscience and the importance of social factors in philosophy and human life.  Here are my notes from his 18 minute recent TED talk:

Politicians are all "emotional freaks" of one variety or another

They have a "logodementia"--Talk so much they drive their self insane

But they do have exceptional social skills

Mitt Romney anecdote--able to remember names of everyone he met in the diner

However, in making political decisions this social skill is of little assistance

We have made little progress in education

People learn from people they bond with emotionally

Why are politicians dehumanized when talking about policy?

We have pushed out emotion in making decisions about our lives

We have lost the ability to understand the importance of character and we have lost the ability to talk about using our social intelligence

We pressure our children to jump through competitive hoops

We don't emphasize the importance of developing a philosophy of life

Cognitive neuroscience is providing insight into a new way of thinking about life:

1.) The unconscious mind does most of the work--The unconscious mind is quite smart

2.) Emotions are at the center of our thinking (Antonio Dimasio speaking on this issue later in the TED program)--Brain is a record of our entire life feelings

3.) We are deeply social animals-our brain and thinking are connected to those around us

How do we see human capital?

Reason is often week, sentiments are strong and trustworthy

For humans to thrive humans need:

Mind sight--ability to see into the minds of others and understand their thinking (ability to attach to other versus an avoidant att

Equipoise--having the serenity of analyze are our own biases

Street Smarts--ability to pattern recognize and 

Sympathy--the ability to work in groups on common task--group effectiveness not affected by 

Blending--using diverse view points to blend a new way of thinking

Limericks- unconscious mind hungers for moments of transcendance--these moments occur in relationships with our closest relationships

David has a NY Times bestseller book in this topic area: The Social Animal.  I have not read the book and so can not comment on it's merit.  It is on my future reading list as soon as a copy is available at my local public library.

The Calorie Restriction Myth

As you'll know if you've read THIS FREE EBOOK, I'm not exactly a fan of low-calorie eating.  While I'm tempted just to say, "aw man, calorie restriction.  That is so dumb, that is really dumb, fo real" - I figured it would be better to seriously address calorie restriction as I see it.  Recently I wrote a summary of the importance of metabolism that should be appearing on another site soon.  In that summary I addressed calorie restriction briefly, which I have included below. 

The infatuation with calorie restriction is actually a fantastic example of some fragment of research taken out of context and the subtle nuances ignored - and more importantly, it's applicability in real people in the real world unacknowledged.  Of course, when calories are restricted, everything is restricted - you can't say it's purely the restriction of calories as opposed to the restriction of methionine, or polyunsaturated fat, that yielded the prolongation of life.

But far more important than just some academic discussion about the subtleties, an animal in a laboratory is not a human being with free will and free access to unlimited amounts of calorie-dense food.  A two-word summary of calorie restriction with real human beings living in today's society is "it backfires."  Recommending calorie restriction for health and longevity would be like forbidding condom use and recommending abstinence for dealing with population control and the spread of sexually transmitted diseases.  In theory it would work with 100% effectiveness.  Laboratory study would reveal time and time again that abstinence leads to a birth rate of 0.  I think you see what I'm saying. 

Anyway, these are the main points of contention with the silly idea of calorie restriction for health enhancement and longevity.  #5 in particular is a unique point that is lost in translation between laboratory and real world...

An increasingly popular myth is the idea that it’s good to have a low metabolism – and that if we burn energy more slowly we will live longer. Much of this stems from laboratory research showing that severe calorie restriction (like eating half of what you normally eat) prolongs life in several species like fruit flies, rats, monkeys…


But, like most research, this prolongation of life is taken completely out of context and then turned around and applied to adult humans living and interacting in the real world. It ignores aspects of drastic and game-changing significance like…

1) The only people successful at permanently reducing calorie intake by at least half are those that develop an eating disorder (and dieting at a young age is the top “risk factor” for developing an eating disorder), the deadliest known psychological disease that affects 11 million Americans alone, mostly young women – and globally has killed more people than the Holocaust.

2) Humans are surrounded by endless abundance and temptation for food, and with real people in the real world, cutting calories by half leads to massive rebound hyperphagia (pigging out – as is seen in yo-yo dieting and every human calorie-restriction trial ever conducted).

3) Calorie restriction experiments are done with animals from birth. This is a hugely significant difference, and the bodies’ of the creatures can develop at a rate that makes the low calorie intake sufficient – but this calorie intake is insufficient and causes rapid degeneration when the calorie level is cut after adulthood has already been reached. Comparing calorie restriction from birth to calorie restriction begun in adulthood is a completely invalid comparison.

4) Calorie-restricted laboratory animals display many characteristics of neurosis, anxiety, and social/behavioral disorders (like those with eating disorders). Thinking that cutting calories will lead to a long and prosperous life in a human is total fantasy that ignores what science and real world observation has already shown us.

5) A laboratory is a sterile environment, and even if the calorie restricted animals lived longer and did have a verifiably slower metabolic rate (pound for pound I don’t think they do), it’s hard to compare this to the real world. The real world is filled with opportunistic organisms and other pathogens, and a high metabolism controls the strength of the immune system completely. A high body temperature – a result of a high metabolism, protects from invasion just like a fever wipes an infection out. More importantly, it is obvious when looking at the real world what happens when food becomes scarce – famines lead to widespread disease and infection at astronomically higher rates.  Of course, the body of research connecting degenerative disease like many autoimmune diseases and cancers to various infections is growing rapidly. 

“In some animal forms, at least, chronic undernutrition prolongs the natural life span.  It has been suggested that the natural life span is fixed, not in time, but in terms of total metabolism or some function of the rate of living.  But in man severe undernutrition makes him look, feel, and act prematurely old.  There are also changes in basal metabolism and in sexual function which resemble those produced by age."
-Ancel Keys

"Calorie restriction is friggin' retarded."
-Matt Stone 

The Challenge of Screening for Bipolar Disorder

Reliable and valid self-administered screening tests for depression and many of the anxiety disorders have been around for many years.  However, development of a good screening instrument for bipolar affective disorder has been disappointing.  Although several instruments have been proposed as reasonable for clinical care, there is limited psychometric support for widespread utilization.

The Mood Disorder Questionnaire (MDQ) is one of the most widely studied of the questionnaires that screen for bipolar disorder.  Although, it has some evidence of validity when tested in patients with well-established mood disorders, it has received very limited studies in more challenging screening populations, i.e. general psychiatric outpatient clinics or primary care clinics. 

Dr.  Mark Zimmerman and colleagues from Rhode Island Hospital and Brown Medical School recently published an analysis of the reliability and validity of the MDQ in a series of 752 psychiatric outpatients.  Dr. Zimmerman has been conducting tremendous research in the psychometrics and diagnosis of a variety of mental disorder for over 20 years.  I trust his work and given that he did not develop the MDQ, I think he is likely to be unbiased in this type of research.

Sensitivity and specificity are two key components of a good screening testing.  Unfortunately as one increases, the other decreases and so determining a cut point for screening test is a compromise between false negatives and false positives.   The sensitivity for a screening test is commonly set for 90% meaning that 90% of the population with the disorder (i.e. bipolar disorder) would screen positive with the screening test.

In the Brown University study of the MDQ in a general psychiatric outpatient population:

• Several cut points were  analyzed for sensitivity and specificity of bipolar disorder as defined in a comprehensive DSM-IV interview all outpatients received
• A cut point that provided a 90% sensitivity was defined and implemented (this cut point resulted in a 61% specificity)
• Unfortunately the positive predictive value using this cut point was only 22.1%--meaning of all those that had a positive screen, only 22% in fact had bipolar disorder

The authors note that the MPQ (and all other bipolar disorder screening tests) do not appear to be add sufficient value to general psychiatric practice.  They note that competent clinicians asking the diagnostic criteria are unlikely to find benefit in routine clinical practice.  There may be some slight benefit in that those screening negative may require less attention in further assessment of bipolar disorder risk.  But this minimal benefit is probably offset by the time and energy needed to administer and score the questionnaire.

The authors also note that for primary care physicians with little psychiatric training, the MPQ may aid in identifying patients at risk for bipolar disorder who may need referral for further evaluation.  Primary care screening for bipolar disorder should occur in the context of collection of screening test data for the more common conditions of depression, anxiety disorder and substance dependence.

Photo of St. Louis Cardinal Albert Pujols batting in spring training game against the Minnesota Twins in 2011 in Jupiter, Florida.

Zimmerman M, Galione JN, Ruggero CJ, Chelminski I, Dalrymple K, & Young D (2011). Are screening scales for bipolar disorder good enough to be used in clinical practice? Comprehensive psychiatry PMID: 21406301

Joanne Unleashed

Just when you thought you couldn't possibly be more sick of hearing me talk after yesterday, here's another interview conducted a couple of weeks ago that was released on Monday.  It was with Joanne, a fellow health nerd like us, who has truly put together some fantastic and very diverse interviews including Kilmer McCully and Jon Gabriel just to name a couple.  I haven't listened to the interview yet, but hopefully it came out pretty good.

Listen to our conversation HERE

After signing up for Joanne's site via her free membership, you'll be able to access it. 

P.S. - Sorry for my absence in the comments this week.  My sister, oldest niece, and Eat the Food niece are in town, and there's sand on the beach that needs to be held down.  I will be back full throttle next week, and will be doing a short post tomorrow-ish. 

Cognitive Biomarkers in Eating Disorders

I previously posted on a review of the neuropsychological domain of set-shifting as a possible biomarker for eating disorders.  In that post, set shifting as measured by the Wisconsin Card Sort tests was impaired in those with an anorexia nervosa and continued impaired despite weight restoration.  Additionally, sisters of those with an eating disorder, also showed some impairment on this measure even when they had no eating disorder problem.  This supports a potential role for set shifting as a potential biomarker for eating disorders.

Now an additional study of neuropsychological performance in women with eating disorders and their healthy sisters has been published in the journal Comprehensive Psychiatry.  In this study, the authors examine two computerized tasks tapping the symmetry of performance of the brain’s left and right hemisphere.   

The test of right hemisphere function involved a two-bar visual bar graph stimulus.   Participants were asked to identify the presentation as odd or even dependent on the location of an indicator arrow.  In the test of left hemispheric function task, four letter strings were presented and participants were asked to identify the words as real work or a pseudoword.

The subjects with eating disorders included young women with anorexia nervosa, restricting subtype, anorexia nervosa, binge-purge subtype and bulimia nervosa.  The neuropsychological tests were assessed for accuracy and speed of response.  The key finding from the study were:

• Patients with eating disorders showed higher error rates and slower response times on tests of both the right and left hemisphere
• Anorexia nervosa, restricting subtype tended to be associated with the greatest level of impaired functioning
• Sisters of the eating disorder subjects also showed impairment despite scores similar to controls on measures of depression, impulse control, obsessional thinking and eating disorder symptoms

The authors note that there results support “general individual differences in cognitive processes that may run in families, irrespective of the eating disorder condition of the family member”.    The authors also note that their findings support the continuum model of eating disorders proposed by Michael Strober.  This model proposes that anorexia nervosa, restricting subtype is the most severe category of the eating disorders with bulimia nervosa being the least severe (on a general basis, it is possible for some individuals with bulimia nervosa to have a more severe eating disorder than some individuals with anorexia nervosa, restricting subtype).   The data from this study indicate the anorexia nervosa restricting subtype demonstrated the most severe neurocognitive impairment with bulimia nervosa the least impairment.

Look for more studies examining neurocognitive function in those with eating disorders.  Strategies that combine neuropsychological assessment with fMRI and genetic data may be the most powerful strategy for research in these disorders.  


Photo of rescued sea turtle from the Loggerhead Marine Center in Juno Beach, Florida courtesy of Yates photography

Rozenstein MH, Latzer Y, Stein D, & Eviatar Z (2011). Neuropsychological psychopathology measures in women with eating disorders, their healthy sisters, and nonrelated healthy controls. Comprehensive psychiatry PMID: 21397219

Chick'n Chili Verde Soup

 You are all going to love my latest soup creation "Chick'n Chili Verde Soup".  It is absolutely delicious and can be served with some homemade wholegrain breadsticks (shown above), or some healthy tortilla chips crushed into the soup.  Also, don't forget your raw organic greens on the side.  I started this soup creation by using one piece (2.5 oz.) from the product Gardein Chick'n Scallopini. This is a plant-based product that you can find in the frozen section of your health food store. One piece has 2 grams of fat ,14 grams of protein, 30% of your iron needs and 2 grams of fiber. It was a very nice addition to this soup and adds some extra nutrition. I know you and your family are going to love this soup.

Chick'n Chili Verde Soup

Printable Recipe

Serves 4

1 Gardein Chick'n Scallopini Piece (chopped into cubes)
1 tsp. olive oil
1 clove garlic (minced)
1 yellow onion (diced)
1 extra large or 2 smaller tomatillos
1/2 jalapeno pepper (chopped finely)
1/2 red bell pepper (diced)
1 Anaheim pepper (diced)
1 1/2 cups corn (fresh or frozen)
6 cups salt-free vegetable broth (Rapunzel salt-free bouillon)
2 small juiced limes or 1 large lemon
1/2 tsp. coriander
1/4 tsp. cayenne pepper
2 tsp. chili powder
1 tsp. cumin
2 tsp. sea salt
1 Tbsp. agave nectar
2 Tbsp. arrowroot powder (mix with small amount of cold water, then add some hot soup mixture, then add to soup.

1.)  Cut Chick'n piece into small squares.  Put 1 tsp. olive oil in soup pot and cook Chick'n pieces until slightly browned.  Add minced garlic, chopped onion, tomato and peppers.  Cook for 2 minutes stirring carefully.  Add in corn, 6 cups vegetable broth, agave and seasonings.  Bring to a boil and then reduce to simmer.  Mix 2 Tbsp. arrowroot powder with a little cold water.  Then add some hot soup mixture to the arrowroot powder before adding the entire mix to soup.  This will help to thicken the soup a bit. 

2.)  Enjoy with homemade bread sticks or crunchy tortilla strips.

Emotional Processing Bias in Depression

Clinicians and individuals with depression understand the tendency for depression to be associated with over-interpretation of negative cues in the environment.  Depression seems to heighten perception of negative environmental cues including interpersonal (or social) cues.   The cognitive behavioral model of depression emphasizes the cognitive triad—a negative bias (view) of the self, the environment and the future.

Functional magnetic resonance imaging is providing a model to study emotional processing and better understand how this processing may be disturbed in depression.  When shown brief images of emotion-laden faces, subjects suffering from depression show exaggerated responses.  Depressed or angry faces produce heighted amygdala responses in those with depression.  Happy faces produce a blunted amygdala response. 

Teresa Victor and colleagues recently published a study in the American Journal of Psychiatry providing additional information about this emotional processing bias.  (Disclosure:  Dr. Victor is now a neuroscientist with the Laureate Brain Institute-my employer).   She summarized her findings in a recent journal club.  Here are the key findings from her recent research:

• The amygdala response to facial images occurs even with brief subliminal (unconscious) presentations
• Sad facial images activate the amygdala in depressed subjects (compared to controls) in both those with active and remitted depression
• Happy facial images activate the amygdala in controls more than depressed subjects
• Eight weeks of selective serotonin reuptake inhibitor therapy (sertraline) reverse  (normalize) the amygdala response to facial emotion cues

 The authors summarize their findings “These data demonstrate that negative emotional-processing biases occur automatically, below the level of conscious awareness, in unmedicated, currently depressed people…”.  “This nonconscious processing of emotional stimuli is consistent with evidence that the amygdala contains cells that are tuned selectively to specific stimulus characteristics, facilitating early detection of biologically salient information”.

The findings from this research suggest exaggerated amygdala responses to sad faces may be a trait marker and not just due to the presence of active depression.  This might allow this trait to be studied as an endophenotype (or potential genetic marker for depression).    Normalization of this exaggerated response with selective serotoning reuptake inhibitors may provide an additional paradigm for studying the effect of new novel antidepressants.

From the clinical standpoint, this study suggests that negative emotional cues may occur below the level of consciousness in the daily lives of those with depression.  It supports clinical experience that some dysphoria may occur in response to environmental cues patients do not remember (or recognize at the time of the cue).   Further study of emotional processing is likely to advance both the research and clinical understanding of depression and other mood disorders. 


Photo of sea gull over beach at Jupiter Island, Florida courtesy of Yates Photography.

Victor TA, Furey ML, Fromm SJ, Ohman A, & Drevets WC (2010). Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder. Archives of general psychiatry, 67 (11), 1128-38 PMID: 21041614

Conversation with East West Healing

Tomorrow's the big day.  As some of us are delving into this strange new world of eating MORE, not less simple sugar instead of being devout starchatarians, I thought it would be great to have a conversation with Josh and Jeanne Rubin of East West Healing and Performance.  The Rubin's are very well-versed in the use of not just sugar, but also gelatin as a non-inflammatory source of protein added to the diet in signficant quantities (another recent tangent). 

While in the past they've leaned towards metabolic typing and Paleo-ish diets, they have been having great success by following Ray Peat's ideas on fats, protein, and carbohydrates with real people in the real world.  Their results have been fantastic, and I knew it was time to get them on the phone and make them spill the beans as to what exactly they are seeing and why. 

So please join us tomorrow at 1pm Pacific/4pm Eastern for what should be a great, casual conversation between us, and hopefully Josh and Jeanne will open up the lines for many of you to call in and ask questions, share your concerns and personal experiences, and use Karate Kid aliases as was done during my interview with Sean Croxton. 

If you are new to 180, familiarize yourself with THIS FREE EBOOK to understand what a radical idea it is for me to consider sugar as helpful with a long list of health problems when used in the right context. 

The interview with Josh and Jeanne can be found by clicking HERE. 
The call will be recorded so if you can't tune in for it live you can still listen to it later. 

To get a taste of what's to come, watch Josh's recent video on sugar.  Please do not attempt to take your head off, bite it, and put it back on. 

How to Cook Dark Leafy Greens

Just a quick little weekend blurb here...

This is very simple but for some reason, maybe due to my inner Cracker Barrel, I just really love it.  You couldn't pay me to a eat a salad if these greens were sitting next to it. 

To make them all I do is add a couple cups of water to a pot, 1 sliced onion per pound of dark greens (turnip greens are the best - hellfire that's what they serve at Cracker Barrel, but this works well for collard greens and various types of kale as well as mustard greens and others), plenty of the infamous MONEY SPICE, and cook them for at least an hour at a very low simmer, if not a hair longer.  This was filmed a couple of months ago and now I'm cooking them even longer! 

I consume all of the greens as well as the broth which is tasty and full of minerals which I'm all about.  In fact, next time I make these I'm considering using a little chicken stock instead of water and/or adding a couple ounces of powdered gelatin at the end - stirring it in until it is dissolved but not boiling the hell out of it.  It could be part of my gelatinophilia experimentation.  For you real rednecks (Johnny Lawrence), throw a frickin' hambone or a couple pig's feet up in there.  Mercy.   

Exercise May Reduce Appetite But Increases Calorie Consumption

The relationship between exercise, appetite and food intake is a complex relationship.  Aerobic exercise has been touted as a way to reduce appetite potentially increasing weight loss.  This effect has been termed the anorexia of exercise.  The effect appears to be commonly found after exercising at greater than 60% of maximum oxygen consumption.  This decreased appetite after exercise has been  possibly due to the redistribution of blood flow from the gastrointestinal tract to the peripheral muscles.   However, a temporary reduction in appetite following exercise may not actually correlate with a reduced caloric consumption over a more extended period of time.

Derek Laan and colleagues from Purdue University and the University of Missouri recently published a further look at the relationship between exercise, appetite and caloric intake.  In addition to aerobic exercise, they examined the effect of resistance exercise on appetite and calorie consumption.  The key issues in the design of this study included:

• Subjects: Male and female from the Purdue community, ages 18 to 29, BMI between 18 and 29 (normal weight to overweight but obesity excluded), percent body fat less than 20% for men and less than 35% for women, not currently dieting with no recent weight loss/gain, nonsmokers, nondiabetic and exercising at least twice per week for 30 minutes in each of aerobic and resistance categories.
• Experimental Design: Three sessions: 1.) one aerobic session of 35 minutes cycling at 70% maximum heart rate, 2.) one resistance training session of 35 minutes including 3 sets of 5 weight lifting exercising at 75% maximum, 3.)  a control session of no exercise
• Appetite and Calorie Consumption:  1.) Perceived appetite rated before and after exercise using 13 point scale with 1=not at all hungry and 13=extremely hungry, 2.) Thirty minutes after exercise subjects were given 30 minutes to consume a pasta salad meal with instructions to eat as much or as little as desired until feeling comfortably full.

The key results of the research included:

• Aerobic exercise but not resistance exercise reduced hunger ratings 10 minutes after exercise.  The effect lasted about 30 minutes when hunger ratings returned to levels experience by resistance exercise and controls
• Mean caloric meal intake was 897 calories for aerobic exercise group, 924 calories for the resistance exercise group and 784 calories for the control group (both exercise groups consumed more than controls—14 to 18% more, a statistically significant amount

The authors concluded that in healthy adults, aerobic exercise does temporarily reduce hunger ratings but the effect is small, transient and not related to reduced calorie consumption in an unrestricted meal setting.  A similar study would be interesting in a group of patients with anorexia nervosa who commonly exercise to excess in an attempt to lose weight and maintain weight below medically healthy levels.   Additionally, similar studies in obese subjects might be helpful in prescribing the best exercise and diet regimens for weight loss.   This study suggests resistance training alone may increase caloric intake more than the calories expended in resistance exercise.   The increase caloric consumption with aerobic exercise probably contributes to the limited weight loss found in starting an aerobic exercise program.

Photo of March 2011 sunrise at Juno Beach, Florida courtesy of Yates Photography.

Laan DJ, Leidy HJ, Lim E, & Campbell WW (2010). Effects and reproducibility of aerobic and resistance exercise on appetite and energy intake in young, physically active adults. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 35 (6), 842-7 PMID: 21164556

Val Kilmer McCully

Okay, his first name is not Val. I added that. Whatever I can do to squeeze in an 80’s movie photo, damnit I’m willing to do it!  He was a "real genius." 

Let’s focus more on McCully. It’s an Irish name. It’s St. Patrick’s Day. Pretty awesome huh? Yeah I know.

What’s the difference between Mick Jagger and an Irish farmer? Mick Jagger says “Hey you, get off of my cloud.” An Irish farmer says, “Hey McCloud, get offa my ewe!”

Okay, serious faces now everyone. Thinking caps…

Kilmer McCully was one of “those” good scientists who challenged the status quo about heart disease. Instead of merely looking at the hypothesis that saturated fat raises cholesterol and then cholesterol jumps into coronary arteries because it has nothing better to do – meanwhile nodding his head, repeating the word “statin” in a catatonic state, and drooling all over his desk…

…Kilmer McCully did what a real scientist does, which is challenge a theory with more loopholes and contradictions than one can even begin to imagine (and was of course ostracized and cast into scientist purgatory for his heretical findings). Contradictions like, I don’t know, the fact that Australian Aboriginal men have low cholesterol (average less than 190 mg/dl), perfect blood pressure (average 125/77), a BMI of 23.2, and 5,000% more heart disease than butter-lovin’ and higher cholesterol-havin’ French women (that’s 50 times more for you non-mathorexics).

McCully noticed that there was no connection between cholesterol and heart disease, so he actually did do some real scientific work and found something that did play a role in heart disease – elevated levels of homocysteine.

Homocysteine is a type of cysteine found in milk. But not just any milk. Specifically, Harvey Milk. It’s a joke, relax. I’m not going to eat junk food and start shooting people. I’m very sensitive to the gay community. I cried watching Milk and cried even harder watching Brokeback Mountain while the guy in front of me laughed and said “anus” every time they said the name “Ennis.”

Homocysteine is a by-product of methionine metabolism. The amino acid methionine is supposed to be converted to homocysteine and then into cysteine. However, this conversion requires an abundance of three key nutrients: folic acid, B6, and B12 – as well as adequate thyroid. Without those factors, homocysteine levels rise, predispose one to heart disease, cause inflammation, and accelerate the aging process.

But McCully was a real scientist with the ability to think intelligently, so I’m sure he didn’t realize the role of thyroid in any of this…

“For many years deficiency of thyroid hormone secretion has been known to predispose to arteriosclerotic heart disease. In persons with a serious deficiency of thyroid hormone, the ability of the cells of the body to use oxygen is impaired. The basal metabolic rate is slowed in hypothyroidism, and the liver begins to make increased quantities of cholesterol and triglycerides. As a result the cholesterol and lipoprotein levels become elevated, and the risk of coronary heart disease increases… Subtle or marginal deficiencies of thyroid hormone, detected by measuring basal metabolic rate, are found to be widespread in populations with a high risk of arteriosclerotic heart disease.”

Hmmm, sound familiar?  You can read about the importance of thyroid and metabolism in health and disease in THIS FREE EBOOK. 

But the important lesson here from a dietary perspective is pretty simple, and something that many would agree upon to at least some degree. And that would be that eating a diet with an excess of methionine and a bunch of B-vitamin depleted foods with it is a bad combination. This basic idea is not something new. Researchers noted long before the discovery of homocysteine that food is not metabolized correctly when B-vitamin intake is inadequate…

Robert McCarrison, while studying deficiency of various B-vitamins noted…

“…in the absence of vitamins or in their inadequate supply, neither proteins nor fats nor carbohydrates nor [minerals] are properly utilized; some are largely wasted, while others yield products harmful to the organism.”

While Roger J. Williams pointed towards a similar conclusion. This pretty much says it all…

“A large amount of information, based upon carefully controlled scientific experiments, indicated very strongly that vitamin B6 is another key nutrient which is often present in inadequate amounts in the cellular environment of those whose arteriosclerosis is extreme. Experiments with monkeys have yielded clear-cut results. When they are rendered vitamin B6 deficient, they develop arteriosclerosis rapidly. When monkeys are fed diets supplemented with vitamin B6, they have much lower levels of cholesterol in the blood than when these diets are not supplemented. The animals on the supplemented diet eat much more food than the others, and since their diet contains cholesterol, they get far more cholesterol into their bodies. This does not matter, however; the extra vitamin B6 they get allows them to dispose of the surplus, with the result that their cholesterol blood levels are not as high as in those animals that consume less cholesterol.”


And…


“High or low amounts of fats or carbohydrates are not atherogenic providing supportive nutrients, specifically pyridoxine (vitamin B6), are present. But if pyridoxine is not adequately provided, regardless of the relative amounts of fat or carbohydrate, the diet will be atherogenic.”

Of course the joker in all of this is that just eating nutritious foods rich in say, B-12, isn’t necessarily going to give you high levels of vitamin B-12. The human body unfortunately is much more complex. But it certainly won’t hurt to eat vitamin-rich foods in preference to white stuff – especially white sugar and high-fructose corn syrup which, unlike fortified flour and “enriched” rice, contains absolutely no nutrients whatsoever – real or synthetic.

But the concept is simple nonetheless. In the straightforward words of McCully…

“The dietary factors that determine whether blood homocysteine levels are elevated are the total methionine content of the dietary protein and the content of vitamins B6, B12 and folic acid in the diet.”

McCully isn’t a big fan of fats either really, as they do nothing to offset the methionine content of the typical Western diet because they contain virtually no B-vitamins just like refined carbohydrates. Of course, I’ve pointed out many times that your typical American eats up to 50% of calories from refined carbohydrates and another 35% or so from fats, leaving little room for food containing water soluble vitamins.

One solution to this is of course to, as a general rule, consume less methionine-rich animal protein. Methionine restriction in mice, not surprisingly, has shown tremendous life extension. Ray Peat, another real scientist, has postulated that many of the longevity-enhancing effects of calorie restriction have nothing to do with the amount of energy ingested, but more to do with the total quantity of methionine and other amino acids in a similar pro-aging class. And as I’ve argued before over the controversial findings in The China Study in the past, it should be no surprise that animal protein increases health risks when added to the diet of people eating more than half of their calories from refined carbohydrates like rice and noodles.

Methionine is needed in substantial quantities during the growth period of life when we are adding lots of new lean tissue. Perhaps this is why methionine content is so high in say, eggs. Methionine all goes to the muscles and organs where it is concentrated. So, as a general rule, eating muscles and organs naturally lends itself towards a much higher total methionine intake, although not all meats are created equal.

But, as we reach adulthood and no longer have such a high requirement for total protein or methionine, in a conversation about a general “ideal” diet (and such generalizations should never be made for something so individual as a person’s immediate nutritional needs – a major mistake the government makes is not just their dietary recommendations alone, but the fact that they MAKE BROAD, SWEEPING DIETARY RECOMMENDATIONS in the first place), there would be no harm in eating “mostly plants” with plenty of methionine-free gelatin-rich broths in lieu of giant T-bones or perpetuating the newfound American infatuation with lean chicken breast.

There’s no reason to fear methionine of course. You need some, and when you are going to eat some animal foods it’s probably best to get after the most nutritious of the bunch, such as B-vitamin superhero organ meats (I have pate in my fridge, which also protects against nitrate deficiency!), whole eggs, shellfish, and dairy products – particularly cheese which contains a lower concentration of the “bad” amino acids… that part is in the whey that bodybuilders and Mercola are consuming in outrageous quantities.  Same thing with egg whites vs. the yolks. 

And well, you already know how I feel about eating a lot of refined carbohydrates. What I like about McCully’s theory is that it is much more congruent with the observation in all cultures of a widespread health demise occurring when each society was introduced to refined carbohydrates for the first time, with or without other dietary and lifestyle factors.

Anyway I'm outta here.  All this health food talk on St. Patty's Day is filling my mind with visions of ice-cold Guinness.  Here are some other McCully quotes to make your head hurt. No wonder so few people caught on to his theory. He wrote it in language that only a PHD already tied to the cholesterol theory could possibly understand. The final quote about unifying the respiratory, oncogene, and genetic theories of cancer is particularly painful, but interesting nonetheless…

“Current thinking about how homocysteine causes plaques in the arteries theorizes that a buildup of homocycsteine in the body leads to overproduction of a highly reactive form of homocysteine that causes LDL to become aggregated. This reactive form, homocysteine thiolactone, is made from methionine in the liver by an enzyme that participates in the protein formation and by other less well-understood processes. The LDL-homocysteine thiolactone aggregates are released into the blood from the liver. Then these aggregates are taken up by macrophages of the artery wall, many of which are derived from wandering monocytes of blood, to form foam cells of early arteriosclerotic plaques. These foam cells degrade the LDL-homocysteine thiolactone aggregates and release fat and cholesterol into developing plaques. The foam cells also release homocycsteine thiolactone into surrounding cells of the artery wall, affecting the way cells handle oxygen. As a result, highly reactive oxygen radicals accumulate within cells, damaging the lining cells of arteries, promoting blood clot formation and stimulating growth of arterial muscle cells which form fibrous tissue, mucoid matrix and degenerative elastic tissue.

The homocysteine theory explains why populations that consume foods of animal origin with abundant methionine and foods that are highly processed, refined and preserved with depletion of B vitamins are susceptible to arteriosclerosis.”

p. 86

“Another very interesting feature observed in cell cultures from children with homocystinuria is the distinctive pattern of growth, which resembles the pattern of growth of cancer cells in culture. Furthermore, the muscle cells of arteries grow in a similar pattern in early arteriosclerotic plaques. As explained in Chapter 2, the 19th century German pathologist Rudolf Virchow likened the increased numbers of muscle cells in atheromas to tumors of the blood vessels. In some way, abnormal homocysteine productions induces cells to lose control of growth processes, causing growth of muscle cells in arteriosclerotic plaques. Recent experiments have shown that homocysteine damages cultured endothelial cells and increases the growth of smooth muscle cells. These effects on the cells of artery walls explain in a general way the early phases of production of arteriosclerotic plaques.”

p. 96

“The origin of arteriosclerosis is now understood to be a toxic effect of a by-product of protein breakdown, the amino acid homocysteine. The importance of fats and sugars in the genesis of the disease is now understood to be related to loss of vitamins B6 and folic acid through processing, refining and preservation of foods, creating an imbalance between the abundant methionine of foods of animal origin and the amount of these essential vitamins necessary to prevent a buildup of homocysteine in the body.”

p. 213

“In summary, the discoveries of the role of homocysteine thiolactone, thioretinamide, thioretinaco and thioco in malignant cells offer a new way to unite the respiration, genetic and oncogene theories of the induction of cancer. The loss of thioretinaco ozonide from cell membranes leads to the abnormal respiration of mitochondria in malignant cells, with secondary accumulation of reactive oxygen radicals. The loss of thioretinaco also allows excessive synthesis of homocysteine thiolactone from the methionine, causing aggregation and altered activation of nucleoproteins, abnormalities of cellular membranes, altered immunological recognition and increased growth potential through increased activation of oncogenes and increased formation of thioco.”