Thursday, December 30, 2010

What Can Modern Toxicology Tell Us About Food Toxins and Food Intolerances?

by Chris Masterjohn

"The dose makes the poison." — Paracelsus (1493-1541)
"What is food to one is bitter poison to others." — Lucretius (ca. 99 BC -- ca. 55 BC)

This post will be the first in a series of posts on food toxins and food intolerances.  As an introduction, I'd like to review some of the recent advances in our understanding of toxicology, to see how a basic understanding of toxicology might be able to shed some light on the toxicity of foods.

Although the sayings attributed to Paracelsus and Lucretius above may seem contradictory, taken together they capture two central concepts of modern toxicology.  Some drugs, for example, are just inherently toxic at high enough doses.  Reactions to these drugs are called type 1, type A, or "intrinsic" adverse drug reactions.  Other drugs only produce toxicity in suscpetible individuals.  Reactions to these drugs are called type 2, type B, or "idiosyncratic" drug reactions.  Some authors call them "bizarre" drug reactions (1).  Idiosyncratic reactions are estimated to account for 13% of all drug-induced liver injury (2) and somewhere between 5% and 20% of all adverse drug reactions (1).

In reality, the separation of drugs into some that produce "intrinsic" toxicity and others that produce "indiosyncratic" toxicity is probably an illusion.  For example, acetaminophen (e.g., Tylenol) is the drug most commonly responsible for intrinsic drug reactions, but over a third of people develop clear signs of liver toxicity when taking the maximal dose allowed on the label, while nearly a fifth of people tolerate the dose with complete impunity (3). 

One review (4) recently argued that all drugs have a therapeutic curve and a toxicity curve, but with drugs whose toxicity is usually called "idiosyndratic" the toxicity curve just lies much further away from the therapeutic curve:

Figure from Roth, R.A. and P.E. Ganey, Intrinsic versus idiosyncratic drug-induced hepatotoxicity--two villains or one? J Pharmacol Exp Ther, 2010. 332(3): p. 692-7.

In the case of the intrinsic reaction, shown at the top, the therapeutic (left) and toxicity (right) curves are fairly close together, so that toxicity predictably develops at a high dose.  However, as indicated by the arrow, individual susceptibility can shift the toxicity curve leftward so that it overlaps with the therapeutic range.  This would allow, for example, someone to develop toxicity taking Tylenol at an approved dosage.

In the case of the idiosyncratic reaction, shown at the bottom, the therapeutic (left) and toxicity (right) curves are very far apart.  Since the liver toxicity curve lies to the right even of the lethal dose, liver toxicity never develops under normal conditions.  However, once again, individual susceptibility can shift the toxicity curve leftward so that it overlaps with the therapeutic range.  This allows the "idiosyncratic" or "bizarre" reaction to occur.

In other words, these aren't two types of reactions, but they are two principles that are important in any toxic reaction: how dangerous the toxin is, and how susceptible the person is.

Food toxicities and intolerances also clearly involve both principles.  On the one hand, celiacs predictably improve in the majority of cases by removing gluten from their diets and many non-celiacs benefit as well.  On the other hand, many people eat grains, beans, peanuts, salicylates, oxalates, glutamates, amines, polyphenols, barbecued meat, bacon, and every other potentially toxic food and food chemical with impunity until they die at a ripe old age, sometimes over the age of 100.

What, then, contributes to this individual susceptibility?

Let's turn again to modern drug toxicology and see what we find. 

Here are a few of the well studied factors that contribute to individual susceptibility:

Nutritional Status.  Acetaminophen causes toxicity in part by causing a massive 90% depletion of glutathione, the master antioxidant and detoxifier of the cell.  (See my related blog post, "The Biochemical Magic of Raw Milk and Other Raw Foods: Glutathione.")  The standard treatment is N-acetyl-cysteine, a highly bioavailable form of the amino acid cysteine, which our cells use to make glutathione.  It is especially effective at mitigating the toxicity of acetaminophen when provided during the first ten hours of toxicity (5).

Intestinal Flora. In the 1970s and 1980s, researchers provided compelling evidence that the mechanism by which galactosamine, carbon tetrachloride, and halothane produce liver toxicity is by causing the movement of endotoxin from the gut into the bloodstream (6).  If they added endotoxin, the toxicity increased.  If they provided any number of materials that "mop up" endotoxin in the intestine, without adding any additional endotoxin, they could prevent the toxicity of these chemicals.  Nowadays, researchers are investigating the role of endotoxin in priming a person to idiosyncratically react to the antidepressant chlorpromazine, the antihistamine ranitidine, the antibiotic trovafloxacin, and several NSAIDs.  Endotoxin is a component of the cell wall of gram-negative bacteria.  Many stressors can temporarily increase the transport of endotoxin across the intestinal barrier, while probiotics decrease the levels of endotoxin in the intestine.

Genes.  C57BL/6 mice are used for many experiments.  Although researchers often make additional genetic modifications to these mice, they are actually already genetically defective: they have a genetic deficiency of the enzyme that converts the B vitamin niacin from its NADH form to its NADPH form, which is needed to recycle glutathione (7).  Researchers have further used these mice to create a deficiency of the maganese-dependent enzyme superoxide dismutase, which, like glutathione, is critical to the cell's natural antioxidant defense system.  These mice suffer from poor mitochondrial function as a result.  They develop toxic reactions to flutamide (7) and troglitazone (8), two drugs that are considered "idiosyncratic" and are otherwise difficult to use to produce toxicity in animals.  About one in 5,000 people have a similar genetic mutation, although many people may have poor mitochondrial function for nutritional, lifestyle, and other reasons.

Immunological Reactions.  About a fifth of idiosyncratic liver toxicity is associated with immunological signs and symptoms such as eosinophilia (an increase in a certain type of immune cell in the blood), rash, fever, and autoimmune  antibodies or antibodies to drug-modified proteins; when these occur, they generally occur within one to six weeks after beginning the drug (9).  Some authors argue that the immune system could confuse "self" and "nonself" when toxic drugs form complexes with proteins, causing the immune system to recognize the protein itself as toxic (10).  Others argue that the immune system does not have anything to do with recognizing "self" or "nonself" but instead recgonizes "danger," and that it is tissue damage that causes the immune system to come along and clean up the mess, including cleaning up our own proteins when they are damaged or spilling out where they don't belong (11).  The role that these immunological reactions play in toxicity, whatever their cause, remains obscure.

This is not a comprehensive list of factors that affect drug toxicity, but it contains some of the most important kinds of factors, and gives us a clue what types of things to look for when understanding why some foods are toxic.

Here's a brief outline of some of the factors that are most likely to be involved in food toxicity and food intolerance:
  • The intrinsic toxicity of the food. 
  • Proper preparation of the food to neutralize the toxins.
  • Genetic, and perhaps epigenetic, variations in the activities of enzymes and other proteins that activate the toxin, detoxify the toxin, transport the toxin, or mount an immunological response to the toxin.
  • Variations in intestinal flora, including bacteria that degrade the toxin or bacteria that counteract the body's detoxification mechanisms.
  • Secretion of sugars such as mannose into the digestive system that bind to lectins (such as gluten) and protect against their toxicity.
  • Secretion of IgA antibodies into the intestinal tract, which bind to undigested food particles and protect against their toxicity.
  • Variations in nutritional status, including nutrients involved in modulating the immune response, supporting detoxification mechanisms, and protecting the integrity of the gastrointestinal tract.
How these factors should be expected to affect the toxicity of wheat, other grains, beans, oxalates, amines, salicylates, and various other foods and food toxins will be the subject of upcoming blog posts.

Stay tuned!

Read more about the author, Chris Masterjohn, PhD, here.


1. Pirmohamed, M., Pharmacogenetics of idiosyncratic adverse drug reactions. Handb Exp Pharmacol, 2010(196): p. 477-91.

2. Holt, M. and C. Ju, Drug-induced liver injury. Handb Exp Pharmacol, 2010(196): p. 3-27.

3. Watkins et al., Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):87-93.

4. Roth, R.A. and P.E. Ganey, Intrinsic versus idiosyncratic drug-induced hepatotoxicity--two villains or one? J Pharmacol Exp Ther, 2010. 332(3): p. 692-7.
 5. Hinson, J.A., D.W. Roberts, and L.P. James, Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol, 2010(196): p. 369-405.

6. Lind, R.C., et al., The involvement of endotoxin in halothane-associated liver injury. Anesthesiology, 1984. 61(5): p. 544-50.

7. Kashimshetty, R., et al., Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicol Appl Pharmacol, 2009. 238(2): p. 150-9.

8. Ong, M.M., C. Latchoumycandane, and U.A. Boelsterli, Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. Toxicol Sci, 2007. 97(1): p. 205-13.

9. Pachkoria, K., et al., Genetic and molecular factors in drug-induced liver injury: a review. Curr Drug Saf, 2007. 2(2): p. 97-112.

10. Pessayre, D., et al., Mitochondrial involvement in drug-induced liver injury. Handb Exp Pharmacol, 2010(196): p. 311-65.

11. Li, J. and J.P. Uetrecht, The danger hypothesis applied to idiosyncratic drug reactions. Handb Exp Pharmacol, 2010(196): p. 493-509.

Tuesday, December 28, 2010

Review of Paul and Shou-Ching Jaminet's "Perfect Health Diet"

by Chris Masterjohn

Paul and Shou-Ching Jaminet's The Perfect Health Diet is a great book.  I have discussed some caveats, but ultimately I think it is excellent and many people would benefit from reading it.  You can read my review here:

Paul and Shou-Ching Jaminet's The Perfect Health Diet

If you'd like, come back and post your comments here!

Read more about the author, Chris Masterjohn, PhD, here.

Monday, December 27, 2010

Yummy Low-Carb Gluten-Free Coconut Flour Pancakes

by Chris Masterjohn

These pancakes are surprisingly pancake-like and delicious when one considers how little carbohydrate is in them.  And, of course, they're gluten-free.

They're from Cooking With Coconut Flour: A Delicious Low-Carb, Gluten-Free Alternative to Wheat, by Bruce Fife, ND.

2 eggs
2 tablespoons coconut oil or melted butter
2 tablespoons coconut milk or whole milk
1 teaspoon sugar
1/8 teaspoon salt
2 tablespoons sifted coconut flour
1/8 teaspoon baking powder

Blend together eggs, oil, coconut milk, sugar, and salt.  Combine coconut flour and baking powder and thoroughly mix into batter.  Heat 1 tablespoon of coconut oil in a skillet.  Spoon batter onto hot skillet making pancakes about 2.5 to 3 inches in diameter.  Batter will be thick but will flatten out when cooking.  Makes about 8 pancakes.

Pecan Pancakes  Make pancakes as directed above and add 1/2 cup of chopped pecans.
Blueberry Pancakes Make pancakes as directed and, after mixing in the coconut milk, fold in 1/2 cup of dry fresh blueberries.


Read more about the author, Chris Masterjohn, PhD, here.

Saturday, December 25, 2010

Merry Christmas!

by Chris Masterjohn

Since political correctness is about as traditional as soy oil, and since joy and happiness are almost certainly as paleo as intermittent fasting, I would like to wish you all...

Merry Christmas!

Reducing expression down to the lowest common denominator will make for a very dull and boring world, whereas we will all be happier if we learn to appreciate the well wishes of others, and to share our joy with others, so I'd like to invite anyone celebrating Christmas, Saturnalia, your birthday, or some other feast, those who recently celebrated Chanukah and those about to celebrate Kwanzaa to, if you would like, use the comments section to share your holiday wishes with the rest of us!

Read more about the author, Chris Masterjohn, PhD, here.

Friday, December 24, 2010

Everything We Thought We Knew About Vitamin D And Latitude Might Be Wrong!

by Chris Masterjohn

New blog post over at WestonAPrice.Org on why everything we thought we knew about vitamin D and latitude might be wrong:

Vitamin D -- Problems With the Latitude Hypothesis

Read more about the author, Chris Masterjohn, PhD, here.

Wednesday, December 22, 2010

Back on Jimmy Moore's Show on January 5th! Thanks for voting!

by Chris Masterjohn

Thank you so much to everyone who voted for me as one of Jimmy Moore's "best of the year" podcasts.  I made it into the top five, along with the frightfully fructocidal Robert Lustig, the deliriously delightful Denise Minger, the illustrious Kurt Harris and the wonderful and consistently well slept Robb Wolf.

We'll each be making a second appearance on Jimmy's Livin' La Vida Low-Carb Show for Encore Week this January.  Here's the schedule:
  • EPISODE 429–January 3, 2010–ENCORE WEEK INTERVIEW #1–Dr. Robert Lustig
  • EPISODE 430–January 4, 2010–ENCORE WEEK INTERVIEW #2–Denise Minger
  • EPISODE 431–January 5, 2010–ENCORE WEEK INTERVIEW #3–Chris Masterjohn
  • EPISODE 432–January 6, 2010–ENCORE WEEK INTERVIEW #4–Dr. Kurt Harris
  • EPISODE 433–January 7, 2010–ENCORE WEEK INTERVIEW #5–Robb Wolf
See you in the podcastosphere soon!

Read more about the author, Chris Masterjohn, PhD, here.

Saturday, December 18, 2010

Can Christians Be Paleo? Christianity, Faith, Evidence, Dobzhansky, Evolution, and More

by Chris Masterjohn

Jimmy Moore recently raised the question, "Can a Christian Follow A Paleo Low-Carb Diet?"  He raised the question because he has received emails from people who find it difficult to answer why God created grains if they are bad for us, why God put Adam and Eve in the Garden of Eden eating a vegetarian diet if we are not meant to eat such a diet, and why the Bible would emphasize bread both in meals and metaphors if it is so awful.  He provided insights from several paleo researchers and bloggers, most of which focused on evidence for evolution and the ability of the Bible to be wrong, and only one of which was from a Christian, which stated that Genesis 18 proves that any meal God personally eats contains protein and fat.

I would like to offer my own take here, which is a synthesis of my views on nutritional science and what I believe is the most genuine, ancient, and traditional appraoch to Christianity.

The crux of this view is this:

Jesus said, "Learn from me, for I am meek and humble in heart," but he did not say, "Learn from me, for I eat fish and bread."

More broadly, this post will cover the following: why you can be a creationist and still eat paleo; why you can be a Christian and believe in evolution; the relationship between faith and science; the proper approach to understanding the Bible; what, if anything, the Bible teaches about how we should eat; a glimpse of some interesting Christian hunter-gatherers from our own continent; and how Loren Cordain accidentally introduced many in the paleo community to an ancient form of Christianity often overlooked in the modern West, and how he completely forgot to point that out.

I realize that religion is a touchy subject, and I am not trying to force any of the non-scientific information in this post on anyone else.  Please feel free to take what you find interesting and leave the rest, and to speak your mind and heart as much as you wish in the comments. 

Paleo As a Heuristic, Not a Diet or Dogma

While some people may see paleo as a definitive diet and argue something along the lines of "paleolithic man ate fill in the blank, therefore I will eat fill in the blank, and if you don't eat like me you will die an early death," the wisest people within the paleo movement do not treat the paleo principle this way. 

Wise people within the paleo movement treat the paleo principle, the idea that the diet and lifestyle of our distant ancestors provides critical information about how we should eat and live, as a heuristic.  In other words, they treat it as a mental model or framework through which they organize information, develop hypotheses, and then test those hypotheses with personal experience and science. 

Richard Nikoley of the Free The Animal blog articulated this in his post, "The Paleo Principle Is Neither Authoritative Nor Dogmatic."  Richard runs an excellent and widely popular paleo blog, but refuses to eschew the modern white potato.  He is also a very happy atheist, even though atheism, as Ned Kock recently pointed out, is a recent neolithic invention.  Of course, it is important to note that Ned defined "atheism" loosely as non-spiritualism and Richard is not against all forms of spiritualism per se.  Richard learns what he can from what he considers the best science of the paleolithic era, but he doesn't pay unthinking subservience to what that science uncovers.

Stephan Guyenet of the Whole Health Source blog likewise refuses to eschew the potato, and while he often incorporates paleo perspectives into his posts, he provides rigorous and objective scientific analyses of everything he posts about, and frequently incorporates information generated by other ideas as well as by paleo. 

Melissa McEwen, who co-organizes the Eating Paleo in NYC meetup group with John Durant, with whom she has also been featured in the New York Times, recently made several posts, including "How Do I Love Thee, Neolithic Foods," emphasizing the need to evaluate ideas generated by the paleo principle with solid science.

Thus, we arrive at the question, must someone who rejects the heuristic used to generate ideas and results also reject those ideas and results?  Certainly not. 

Consider, for example, some of the ideas we currently hold to that were generated using Biblical literalism as a heuristic. 

Most of us are familiar with continental drift theory.  I was first taught in fourth grade science class that all the current land masses were originally one land mass and have since separated by sea-floor spreading and the resulting drifting apart of continents.  Let's take a moment to consider how this theory formed:
The first credible proponent of continental drift was Antonio Snider-Pellegrini, a belated advocate of catastrophism who, in 1858, ascribed the biblical flood to the former existence of a single continent that was torn apart to restore the balance of a lopsided Earth.
That a single land mass existed "in the beginning" is implied by Genesis 1:9 and its division after the flood could potentially be read into Genesis 10:25, but Snider-Pellegrini also provided observational evidence for the theory, including a map of how the continents could have fit together and how the fossils of plant and animal life at the edges of these continents fit together similarly.

Would any of us reject the theory of continental drift simply because one of its early proponents used a Biblical heuristic to shape it?  Of course not.

Why, then, should a Christian who believes the earth is roughly 6,000 years old and that humans have no common ancestry with apes or any other creature reject dietary principles developed within the paleo framework if, in fact, they are validated by modern science and are helping people improve their health?

The answer is that there is no reason.  Just like folks who believe the earth is billions of years old should feel free to accept continental drift and people who accept the paleo principle should feel free to eat white potatoes, people who believe in a young earth and the independent creation of created kinds or species should feel free to eat whatever aspects of the paleo diet they deem likely to help improve their health.

Cordain, Dobzhansky, Evolution, Orthodox Christianity

Loren Cordain wrote the following to Jimmy Moore:
The great evolutionary biologist, Dobzhansky said, “Nothing in biology makes sense except in the light of evolution.”
Cordain could have communicated his point more effectively to the Christians that Jimmy's post was aimed at if he had pointed out what the commenter Patrik pointed out on Richard Nikoley's post:
The only thing I would add to this discussion, if someone else hasn’t already mentioned it, is that evolutionary biologist Theodosius Dobzhansky who wrote the essay: “Nothing in Biology Makes Sense Except in the Light of Evolution” was a devout Russian Orthodox Christian.

Indeed, in the very essay that bears this oft-quoted title, Dobzhansky, generally credited with the modern synthesis of genetics and evolutionary theory, stated the following:
I am a creationist and an evolutionist.

He continued:
Does the evolutionary doctrine clash with religious faith? It does not. It is a blunder to mistake the Holy Scriptures for elementary textbooks of astronomy, geology, biology, and anthropology. Only if symbols are construed to mean what they are not intended to mean can there arise imaginary, insoluble conflicts. As pointed out above, the blunder leads to blasphemy: the Creator is accused of systematic deceitfulness.
He concluded by commenting about Pierre Teilhard de Chardin, a French geologist and paleontologist:

Teilhard was a creationist, but one who understood that the Creation is realized in this world by means of evolution.

Just how devoutly Dobzhansky held to the beliefs of the Orthodox Church is a matter for debate.  Francisco Ayala, who credited him with contributing "to evolutionary biology perhaps more than any scientist since Darwin," described his beliefs in this way:
Dobzhansky was a religious man, although he apparently rejected fundamental beliefs of traditional religion, such as the existence of a personal God and of life beyond physical death.  His religiosity was grounded on the belief that there is meaning in the universe.  He saw that meaning in the fact that evolution has produced the stupendous diversity of the living world and has in fact progressed from primitive forms of life to man.  Dobzhansky beheld that in man biological evolution has transcended itself into the realm of self-awareness and culture.  A metaphysical optimist, he believed that somehow mankind would eventually evolve into higher levels of harmony and creativity.
Ayala offers no citations for these statements and I am therefore unsure of how much more I should trust them than the Wikipedia article that completely ignores them.  Nevertheless, Dobzhansky's personal religious beliefs should not hold captive the religious beliefs of evolutionists or the scientific beliefs of Christians any more than the timeline of the domestication of the potato should hold a paleo dieter captive.

The Orthodox Church, often called "Eastern" or associated with various ethnicities, initially existed as a single multi-ethnic entity in North America.  Owing in part to the loss of Russian financial support as a result of the Bolshevik revolution, it was later broken up into multiple ethnic jurisdictions, contributing to the misconception that it is somehow integrally tied to these ethnicities.  While its distinction from Roman Catholicism and Protestantism owes historically to the divide between eastern and western Christendom that culminated in the eleventh century, Orthodoxy sees itself as continuous with the western church of the first thousand years of Christendom.

While Dobzhansky's faith in the teachings of Orthodoxy may be unclear, many traditionalist Orthodox Christians who take the Church's teachings very seriously do believe in biological evolution.  OrthodoxWiki provides a list of publications by Orthodox Christians with varying views on evolution.

One does not need to look as far as Orthodoxy to find Christians who accept evolution.  Indeed, while Orthodoxy has no official position on evolution, the Roman Catholic church has essentially endorsed it, and there are also many Protestants who believe the same.  Indeed, while the Apostles and most Christians through history seem to have considered the events of the Old Testament to be historically true, even within the New Testament we can see that the overwhelming use of the Old Testament Scriptures has been allegorical and spiritual, considering them to be prophecies of Christ and lessons about the spiritual life.

The Apostle Paul wrote to the Romans, "everything that was written in former times was written for our instruction."  Paul wrote to the Galations that Abraham's two sons were a metaphor for the Old and New Covenants.  The Apostle Peter wrote that the Great Flood represents the saving power of baptism.  Indeed, it is quite telling that Peter refers to the saving power of the water, and not its destructive power.

Thus, it was not difficult even for Francis Collins, head of the Human Genome Project, to convert to Evangelical Christianity, more commonly associated with literalist interpretations of the Old Testament.

While these allegorical interpretations are available to all who use the Christian Scriptures, the rich abundance of allegorical and Christ-centered interpretations of the Old Testament found in Orthodox hymnography would certainly assist many people who question literal historical interpretations of the Old Testament grapple with the meaning of those passages.

When Orthodox Christians begin Lent, for example, they commemorate three stories of exile: the self-exile from Eden, the capativity of Israel to Babylon, and the story of the Prodigal Son.  The story of Eden tells of man's alienation from God and the Prodigal Son tells of his return.  In each story, the exile is self-induced.  Humans leave God, rather than God leaving humans.  Israel's captivity to Babylon represents the captivity of humans to sinful patterns of thought and behavior.  "Sin" is seen in the context of the literal meaning of its Greek word, amartias, which implies the "missing the mark" of divine likeness.  The seemingly gruesome line at the end of Psalm 137 is understood to mean the dashing of angry, hateful, lustful, greedy, selfish, unloving thoughts against the rock of Christ before these "infant" thoughts grow into mental and behavioral patterns that will hold us captive.  Lent, for Orthodox Christians, is thus a time to make the resolve to use this rock for strength, and make the return home to God.

While there is nothing in Orthodox hymnography that indicates these stories are not historical, it would be easy to become immersed in these interpretations and realize that they have meanings that go far beyond the historicity of the events to the point that the historicity becomes of secondary importance, and one is willing to tolerate discussion and debate about the historicity while realizing it has no bearing on the central theme.

Orthodox Christianity may be of interest to those in the paleo community for several other reasons: we have an example of an Orthodox Christian hunter-gatherer population on our own (American) shores; many of the dietary practices of Orthodox Christians have parallels in the paleo community; and Orthodoxy provides some valuable input on faith and reason that may appeal to many scientifically oriented people.

Orthodox Christian Hunter-Gatherers

We hear the story over and over again.  The natives eat traditional diets, have beautiful teeth, well formed dental arches, robust skeletal frames, and they live vibrantly healthy lives.  In come the missionaries, bringing Christ, money, English, flour, and sugar, and it all disappears.

There is an interesting counter-example to this.  The Russians brought Orthodox Christianity to the Inuit and Aleuts native to Alaska in the 1700s.  The missionaries had profound respect for the natives, their culture, and their language, and had very little impact on their diet.  Until the twentieth century, these Christian natives remained hunter-gatherers. 

This topic deserves its own blog post, and I will write about it in the future.  Two books of interest include Fr. Michael Oleska's Orthodox Alaska: A Theology of Mission and Alaskan Missionary Spirituality, a collection of primary source documents that Oleska compiled.  Oleska, though not a native himself, is married to a Yup'ik native and is recognized as an honorary Elder by the Alaska Federation of Natives.

Orthodoxy, Intermittent Fasting, and Protein Cycling

In my recent review of Tim Ferriss's The 4-Hour Body, I discussed Ferriss's comments on intermittent fasting and protein cycling as ways to increase longevity.  Paul Jaminet over at Perfect Health Diet considered these to be "Art De Vany-related ideas."  De Vany is considered the "grandfather" of the paleo movement.

In fact, Orthodox Christians incorporate these concepts extensively, in a way that looks very much like Ferriss's diet.  For example, Ferriss recommends one day a week bringing protein down to 5% of calories and practices 18-hour fasting once a week, eating his first meal around 2:00 PM on Saturdays.  Orthodox Christians eat a near-vegan diet on Wednesdays and Fridays, reducing protein intake to a similar level, and, if they follow the strictest form of these fasts, eat one meal on these days at or around the ninth hour after sunrise, which is generally around 3:00 PM.

Some evidence suggests that Christians have been fasting on Wednesdays and Fridays since the first century.  Some people interested in paleo for its ancientness may also be interested in this practice for its ancientness alone.

Of course, Orthodox Christians have other fasting periods and the purpose has nothing to do with longevity.  Nevertheless, folks worried about the conflicts between Christianity and paleo might also be interested in these points where the two seem to collide.

Incidentally, Nicholas Taleb is a prominent Lebanese Orthodox Christian who considers himself paleo.  Here's John Durant paying him some love.  Here's Taleb appearing in the NYT with Durant and Melissa McEwen.

Orthodoxy On Faith and Reason

Many Christians seem to need "empirical evidence" to support their faith.  This can be witnessed, for example, in the recent Intelligent Design (ID) movement, or the older Creationist movement. 

Personally, I have much more respect for Creationism than ID because the ID'ers seem to believe that God is incapable of making a physical or chemical law that spontaneously leads to marvelous beauty.  If God wanted to create by using evolution, would he really have to constantly intervene in the process?  Is this the same God who can raise the dead, who can't make a self-perpetuating material system?

Regardless of how beautiful the theory is, of course, the desire to provide empirical evidence for it is fundamentally flawed.  Intelligent Design and Creationism are both entirely legitimate theories.  However, neither of them are scientifically testable, and thus one can hardly complain that they are being "expelled" from science.

Here is an excellent diagram from Dr. Kirk Fitzhugh (original source) demonstrating what an experimental test of Intelligent Design might look like:

Since we have no ability to randomize some organisms to the power of God and others to the power of Satan or an intelligence-free control, we can never perform an experiment demonstrating or falsifying Intelligent Design. 

Dr. Fitzhugh has elaborated his criticisms of Intelligent Deign in the journal Evolutionary Biology, available here.

Whether one can test the hypothesis of universal comment descent that underpins what is colloquially called "evolution" is a more complicated question that I will address in a future blog post.

Another example of the search for empirical evidence can be found in Josh McDowell's Evidence That Demands a VerdictWhile I think this book is an interesting read, most of the "evidence" provided in it could hardly nudge a skeptic. 

McDowell: Jesus's tomb is empty. 

Skeptic: That's not Jesus's tomb. 

McDowell: Why did Jesus allow us to believe he is God when there is no evidence he was a liar or insane? 

Skeptic: Who cares?
McDowell's "evidence" contrasts greatly with the evidence that St. Athanasius the Great wrote about in his On the Incarnation in the fourth century.  St. Athanasius considered the masses of martyrs in the preceding centuries to have shown the evidence that Christians did not fear death.  Christ destroyed the power of death with his own death, setting humans free of the fear of death.  Like Paul before him, Athanasius considered faith the "evidence of things unseen."

Would this "evidence" convince a skeptic?  Hardly.  But it makes no pretension to. 

Indeed, anyone with an interest in history, I would think, would at least consider it a rather fascinating curiosity that while Christianity had no state power, it managed to spread through all of western and eastern Europe and into parts of Asia and Africa, when the promise of Christianity was often death in the arena at the hands of gladiators or wild animals.  That Christianity grew in response to persecutions rather than being eradicated is an interesting phenomenon. 

But it's not empirical evidence of anything.  And empirical evidence wasn't really what Athanasius was writing about.

The recent book The Mountain of Silence features a "Fr. Maximos," an Orthodox priest-monk from Mount Athos (the "Holy Mountain," a peninsula of Greece dedicated to monasteries) who is now a bishop of Cyprus, who transmits the teachings of Orthodoxy through dialogue with the author, a sociologist with a western, rationalistic and relativistic mindset that he only partly shakes off by the end of the book.

In the chapter "Knowledge of God," Fr. Maximos explains how logic and empiricism are simply the wrong tests to use in order to obtain knowledge of God:

"Let's assume that we wish to investigate a natural phenomenon.  As you very well know, in order to do so we need to employ the appropriate scientific methods.  If we wish, for example, to study the galaxies, we need powerful telescopes and other such instruments.  If we wish to examine the physical health of our hearts, then we need a stethoscope.  Everything must be explored through a method appropriate to the subject under investigation.  If we, therefore, wish to explore and get to know God, it would be a gross error to do so through our senses or with telescopes, seeking Him out in outer space.  That would be utterly naive, don't you think?"

"Yes, if you put it this way," I replied.  "Can we then conclude that for modern, rational human beings, metaphysical philosophy like that of Plato and Aristotle or rational theology is the appropriate method?"  As I raised the question I thought I knew what Father Maximos's answer would be.

"It would be equally foolish and naive to seek God with our logic and intellect.  . . . Consider it axiomatic that God cannot be investigated through such approaches."

. . . "Does that mean that God cannot be studied?"

"No.  We can and must study God, and we can reach God and get to know Him."

"But how?" I persisted.

Father Maximos paused for a few seconds.  "Christ Himself revealed to us the method.  He told us that not only are we capable of exploring God but we can also live with Him, become one with Him.  And the organ by which we can achieve that is neither our senses nor our logic but our hearts." . . . This is the meaning, Father Maximos argued, of Christ's beatitude, "Blessed are the pure in heart, for they shall see God." 

"Do you understand what that means?  Those who wish to investigate whether God exists must employ the appropriate methodology, which is none other than the purification of the heart from the egotistical passions and impurities."
In modern discourse, we use the word "dogmatic" to mean unthinkingly proclaiming that something must be so while refusing to consider evidence to the contrary.  I believe this comes froma  misunderstanding of the Christian usage.  "Dogma," is, after all, a Greek word.

St. Basil the Great, who many credit with having invented the hospital and orphanage, presided over the Second Ecumenical Council in 381, which finished formulating the last passage of the Nicene-Constantinopolitan, often called Nicene, Creed.  In his work, On the Holy Spirit, he uses the word dogma to mean what the Church proclaims outwardly.  He never contrasts it with evidence.  He contrasts it with kerygma, that which the Church holds in secret as the inner mysteries of the liturgical life and spiritual life.

Indeed, Fr. Maximos would shudder at the thought of anyone believing anything unthinkingly, without evidence, or in the face of evidence to the contrary:

"If people manage to cleanse their hearts and still fail to see God, then they are justified by concluding that indeed God is a lie, that He does not exist, that He is just a grand illusion.  Such people can reject God in all sincerity by saying, 'I followed the method that the saints have given us and failed to find God.  Therefore, God does not exist.'  Dont' you think that would be utterly misguided," Father Maximos continued, "if we believed in a God for whom there was no evidence of existence, a God that was utterly beyond our grasp, a God that remained silent, never communicating with us in any real and tangible way? . . .

"So when during the liturgy we recite the prayer 'I believe in one God . . . ,'" Father Maximos went on after I shifted to second gear, "we try in reality to move from an intellectual faith in God to the actual vision of God.  Faith becomes Love itself.  The Creed actually means 'I live in a union of love with God.'  This is the path of the saints.  Only then can we say that we are true Christians.  This is the kind of faith that the saints possess as direct experience.  Consequently they are unafraid of death, of war, of illness, or anything else of this world.  They are beyond all worldly ambition, of money, fame, power, safety, and the like.  Such persons transcend the idea of God and enter into the experience of God."
With this view in mind, the conversation with the skeptic might go something more like this:

Christian: I love God.
Skeptic: Prove it.
Christian: Come and see.

[Skeptic freely comes to learn or walks away.  Peace remains.]

There is no weakness of faith in this conversation so great that one begins to bend and twist science into proving what it cannot prove. 

And likewise, there is no challenge to faith by open-mindedly considering scientific evidence about the valuable information it may provide about how we can improve our physical health and quality of life.

Conclusion: What Does the Bible Teach Us About Food?

The Bible teaches us that all foods are clean, that in the last days scoffers will come and tell us we can't eat meat, that our bodies are temples of the Holy Spirit, and that we should become partakers of the divine nature so that we be transformed by the Spirit in greater and greater degrees into the likeness of God.

Jesus said, "Learn from me, for I am meek and humble in heart."  He did not say "Learn from me, for I eat fish and bread." 

Moses descended from Sinai, not the great walls of the Food Pyramid.  And he descended with the Ten Commandments, not the periodic table of the elements.

God made the human mind; it should hardly offend God if we choose to use it.  Thus, he has left most of the science to us.

For those specifically interested in the topic of the Bible's relationship to wheat, I would recommend reading some of the cardiologist William Davis's posts on this topic,
here (In Search of Wheat) and here (Ezekiel Said What?).

In future posts, I will provide a series of critiques of Dobzhansky's essay from a scientific perspective, as I have several quibbles with it.  This should prove of interest to creationists, evolutionists, and people who couldn't care less how we got here but are interested in the fascinating story of how twentieth and twenty-first century genetics has pushed us into new understandings that we, stuck in 19th century views of heredity, have stubbornly resisted.

For now, the verdict is: can Christians eat paleo?  Of course they can!

Read more about the author, Chris Masterjohn, PhD, here.

Tuesday, December 14, 2010

Review of Tim Ferriss's The 4-Hour Body Up, Just In Time For Its Release TODAY!!!

by Chris Masterjohn

My review of Tim Ferriss's The 4-Hour Body is now up.  Check it out at this link:

The 4-Hour Body, by Timothy Ferriss

Feel free to come back here and leave comments!

Read more about the author, Chris Masterjohn, PhD, here.

Thursday, December 9, 2010

Why Is My Cholesterol So High On This Diet? You May Be Curing Yourself of Fatty Liver

by Chris Masterjohn

New blog over at WestonAPrice.Org about how a nourishing diet may sometimes increase blood lipids by curing somone of fatty liver disease:

Why Is My Cholesterol So High On This Diet?

Read more about Chris Masterjohn, PhD, here.

Tuesday, December 7, 2010

The Awesomest Paleo Book Ever

by Chris Masterjohn

I wasn't going to reveal this until next year, but I've been inspired by Melissa McEwen's recent review of the worst paleo book ever to reveal my plans to unleash the awesomest paleo book ever in the spring of 2012.  In fact, the more I reveal about this book in coming blog posts, the more and more awesomer it will get.

The book will be entitled The Efficient Evolution Diet: Living Paleo in a Neolithic Age.

The basic premise will be that we can be even more paleo than paleo people could by taking advantage of recent advances in neolithic technology that allow us to fulfill the goals of paleo folks more efficiently.

Here are the basic dietary and lifestyle guidelines.
  •  Essential Fatty Acids.  Paleolithic man ate many fish.  Fish contain omega-3 fatty acids with 5 and 6 double bonds that were likely important in the development of the human brain.  Although the advent of fish farming has allowed man to obtain the same fatty acids in a much more ecologically conscious way, we can now grow these double bonds using far fewer resources by utilizing what I call the corn plant, whose kernels contain similar omeaga-6 fatty acids with 2 double bonds.  Since there are fewer double-bonds, we need to procure corn oil in roughly three times the amount that paleolithic man had to procure fish oil, but corn is not only easier to hunt because it doesn't have any fins, but America also contains vast tracts of land that are otherwise doing nothing but providing forrests for the housing of the excess deer population.  Whereas paleolithic man would have hurt himself trying to shoot these deer with arrows, we can "kill two birds with one stone" by subsidizing the replacement of these forrests with corn fields that can, in turn, be used to provide the essential fatty acids sought after so diligently by paleolithic man in the form of fish.  The United States government has a high credit rating at its disposal that can be used to leverage borrowed money for these subsidies from foreign governments as well as from its own central bank.

  • Carbohydrates.  Our paleolithic ancestors went to great lengths to procure digestible carbohydrates.  In fact, evidence suggests that wild versions of our own plants were so poor in calories relative to fiber, vitamin C, and other nutrients that our [(great)*106]-grandparents had to gather large amounts of these foods just to obtain enough glucose to fuel their brains.  We can now obtain the same quantities of glucose with much less time spent not only gathering but even eating by refining the flours of wheat and other grains.  By simply removing the germ and bran, new technologies can yield large quantities of easily digestible starch.  There is only one problem.  Some evidence suggests that our paleolithic forebears did not consume gluten, a protein in wheat.  Luckily, modern science can again come to the rescue.  A nutritious substance now known as chlorine gas can be used to heavily bleach the flour and destroy the gluten molecule.  In fact, this is one of the reasons that cake flour makes cakes that are so fluffy.  The fluffiness of such cakes also makes eating them much more efficient, as paleolithic man would have taken far more time to chew through the excessively fibrous plants available at the time.  Unfortunately, a very small percentage of the population with gluten intolerance, termed celiacs, still cannot tolerate cake flour.  This problem can likely be avoided by utilizing larger amounts of chlorine gas during the bleaching process.

  • Light and Vitamin D.  Our paleolithic mothers and fathers had much darker skin than modern Caucasians and thus were likely to have much lower levels of a dangerous hormone named vitamin D, which is able to contribute to excess accumulation of calcium.  Those of us with lighter skin can achieve the same results by avoiding sunlight or by using artificial tanning creams.  The world was also far less populated with humans during the paleolithic area, and consequently they used much less energy.  We can obtain similar results by substituting energy-efficient fluorescent lights for more outdated types of illumination.  We can thereby sustain our current population size while consuming amounts of energy closer to those consumed during the paleolithic era.

  • Philosophical Materialism.  Current anthropological evidence suggests that paleolithic people may have been deeply spiritual people.  However, a close inspection of this evidence reveals that the spiritual beliefs developed during the paleolithic era were largely aimed at making sense of the world that paleolithic people saw around them.  We can make sense of the world much more efficiently by using the scientific method and can avoid the interpretive mistakes made by paleolithic groups by rigorously assuming that nothing exists outside of what both a) can be tested by the scientific method and b) has already been tested by the scientific method and shown to exist.  Since we cannot prove a negative, assuming negatives can allow us to maneuver very swiftly around any limitations that the scientific method currently has.  In this way we can achieve the same spiritual goals as paleolithic people, but can do so to a much greater extent with fewer errors.
I have thus far observed the effects of this advanced form of paleo diet in over 3,000 of my patients.  The single side effect I have observed is that some people feel this form of paleo is so efficient that it's "like I'm not even doing paleo."

In most cases, this results in a feeling of enormous success and self-congratulatory behavior.  Overwhelmingly, I have found that my patients' self-esteem increases on this diet.  Occasionally, however, it produces some cognitive dissonance.  I have found that in all cases thus far observed, this dissonance can be resolved by engaging in a highly useful exercise called caveman roleplaying

Dressing up like a real caveman while hunting corn, gathering cake, and musing about the death of religion under fluorescent lights can be an incredibly healthy exercise that can make one shout out "This is easy and I feel like I'm really doing paleo!"

Want this paleo book to get more awesomer?  Give me some feedback! I'd love to hear about your experiences with the Efficient Evolution Diet.  If you send me your picture eating cake in a caveman costume, you may even find yourself on the front cover!

Read more about the author, Chris Masterjohn, here.

The 4-Hour Body by Timothy Ferriss Is Almost Here!

by Chris Masterjohn

I just received my advanced copy of Tim Ferriss's The 4-Hour Body: An Uncommon Guide to Rapid Fat-Loss, Incredible Sex, and Becoming Superhuman.

Tim's last book, The 4-Hour Workweek, was #1 on the New York Times, Wall Street Journal, and Business Week bestseller lists, and has been translated into 33 languages.

Last year, Tim contacted me through Dr. Michael Eades and asked me to write a critique of The China Study for his new book as a case study in junk science. 

It looks like my critique got relegated to the bonus material that will be available on the web site using a password found in the book, which isn't surprising considering the book in its final cut is 571 pages long.  Given how well his last book did, this may prove to broaden the influence of important China Study critiques.  I've updated my original review with links to Denise Minger's critique and my most recent analysis of Dr. Campbell's rat research.

My name is nevertheless found in the index, right below "Mark (weight fluctuation)" and right a above a much more awkward m-word.  On page 512, he discusses my work on Activator X and vitamin K2, the findings of Weston Price, and the important interactions between vitamins A, D, and K2.  He gives a nod to natto, gives goose liver pate a "yum," pays his respects to hard cheeses, and recommends cod liver oil, grass-fed butter, eggs, sauerkraut, and kimchi.

If his chapter on how to get eight hours of sleep in two hours has any merit, I might actually be able to read and review this book before it hits shelves on December 14.

Here's the trailer:

Click here to learn more about the book.  If you think you'll want it, pre-ordering it now will help boost the shelf space that retailers will be willing to use to promote it.

Based on ten years of self-experimentation and interviewing hundreds of elite athletes and dozens of MDs, Ferriss claims a lot of seemingly impossible stuff is possible. If a tenth of the crazy superhuman things he claims are possible actually are possible, this book will be well worth it.  It will certainly be entertaining, regardless.  

Read more about Chris Masterjohn, PhD, here.

Saturday, December 4, 2010

Meeting the Choline Requirement -- Eggs, Organs, and the Wheat Paradox

by Chris Masterjohn

In several recent posts, I argued that most of us aren't getting enough choline, and that the disappearance of choline-rich foods like liver and egg yolks from the modern diet is likely responsible for the silent epidemic of fatty liver disease that may be afflicting 70-100 million Americans.  If you missed them, you can find them here:
In this post, I'll try to outline what we know about how to get enough choline.  And I'll share some surprising insights about the value of spinach, beets, and wheat, with a little discussion of what I'll call "The Wheat Paradox."

Choline in Foods — It's All About the Organs and Eggs

First, let's take a look at where we can get choline from.  The following data is taken from the USDA database (1).  Clearly, liver and eggs top the chart.
Unless stated otherwise, the values are for foods cooked, but without added fat.  Although not shown, most other organ meats probably rank pretty high, especially brain and kidney. 

Interestingly, wheat germ shows up on the list amidst a bunch of animal foods.  This, however, is not the "Wheat Paradox."  It's just the tip of the iceberg.  But more on that below.

Lots of other foods contain smaller amounts of choline.  Here are some of the better ones:

Meats, seafood, and nuts tend to be decent sources of choline, but vegetables are widely variable.  Boiled broccoli, cauliflower, and brussels sprouts have quite a bit of choline, but boiled kale has hardly any. In general, milk and fruit tend to lag further behind the vegetables.  Spices are often decent sources of choline, but are usually used in small amounts.

Clearly, none of these foods come anywhere near organ meats and eggs.  Liver and eggs, for example, have ten times more choline than most vegetables!

By far and away, most of the choline in these foods is found as phophatidylcholine, a membrane-bound phospholipid.  As a result, it's found in the yolk of the egg and not in the white.  A 100-gram serving of egg yolk has 683 mg of choline, whereas a similar serving of egg white has only 1.1 mg.  For an equal amount of each, then, you'd get three times more choline out of your eggs if you threw away the whites.

I haven't found any evidence that heating foods affects the bioavailability of choline.  If you know of any, please post it in the comments section.

Our next question, then is, how much choline do we actually need?  Do we really need to eat egg yolks and liver every day?

The Impossible Question

Unfortunately, trying to estimate how much choline we need is almost impossible for three reasons: 1) there's very little scientific evidence in humans that can be used to justify a particular intake, 2) the choline requirement is dependent on the intake of several other vitamins, 3) the choline requirement depends on certain genetic variations, and 4) the choline requirement is dependent on the intake of several energy sources, such as sugar, alcohol, and fat.  Thus, even if we look to traditional diets, we must attempt to unravel all of these interacting factors.

Nevertheless, there's good reason to think that the choline requirements of both lab rats and humans have been grossly underestimated. 

Lab Rats Are Deficient in Choline

ca. 1976
Gee Brain, whaddya think these pellets are?
I don't know, Pinky. I've never seen them before.
As I pointed out in "The Sweet Truth About Liver and Egg Yolks," choline is capable of completely protecting lab animals against fatty liver induced by sugar, alcohol and fat.  Yet the most common dietary models of fatty liver disease — besides choline deficiency — use high intakes of sugar, alcohol, or fat to induce the disease.  This clearly suggests that choline provided by standard rodent diets is insufficient to allow the animals to deal with these energy sources.

ca. 1993
Gee Brain, what are we going to eat tonight?
The same thing we eat every night, Pinky. Only the sucrose is reduced and the choline is increased 25%!  
The other piece of evidence relates to brain development. As I pointed out in my 2007 Wise Traditions lecture and article on pregnancy nutrition, "Vitamins For Fetal Development — From Conception to Birth," pregnant rat moms fed three times their ordinary choline intake give birth to rat babies with some remarkable lifelong brain-boosting benefits.  They have a 30 percent increase in visuospatial and auditory memory that lasts through their lives; they grow old without developing any age-related senility; they are protected against the assaults of neurotoxins; they have an enhanced ability to multi-task; and they have a much lower rate of interference memory. Interference memory is when a past memory interferes with an immediate memory — for example, when a past memory of where you parked your car interferes with your ability to find it when you exit the store.

The pregnant rat moms consumed this massive dose of choline during the period of gestation in which the choline-based neurons in the brain develop.  In humans, this period of development corresponds to pregnancy and to the first four years of a child's life.  Regardless of whether this enormous brain-boosting effect transfers over to humans, the fact that rats get such a huge benefit from increasing their choline intake so enormously very much supports the idea that current intakes are way too low.

To the Clinical Trial We Go, How Much Choline Humans Need Nobody Knows

For humans, the evidence about our choline requirement was so limited in 1998 that the Institute of Medicine had to set an "adequate intake (AI)" rather than an RDA.  An AI is basically the "let's make a wild guess" version of the RDA.  You can read the report here (2).

The AI is 550 mg/day for men and 425 mg/day for women. It assumes an average male weighs 76 kg  or 168 pounds, and adjusts the male requirement downward for the female requirement as an adjustment for average bodyweight.  It increases to 450 mg/day for pregnant women and 550 mg/day for nursing women.  The increases are based on the typical concentration of choline in a fetus or in mother's milk.  Since there's no reason to think "average" is best, the increases for pregnancy and lactation are basically meaningless.

All these numbers are based on the AI for adult males.  This is taken from a single study (3) that successfully used 500 mg/day to suppress the increase in liver enzymes that occurred in healthy humans eating a choline-deficient diet.  This is almost certainly lower than the true requirement for choline, however.  "Liver enzymes," or aminotransferases, are enzymes that spill out of liver cells into the bloodstream when liver cells start dying.  This can happen as a result of fatty liver, but only when it progresses to a certain stage. 

About 8% of Americans have elevated liver enzymes, roughly a third of which can be explained by known causes such as alcohol, iron overload, or hepatitis viruses (4). But as many as 30% of Americans may have fatty liver (5), and 80% of them have liver enzymes within normal limits (6).  For the final proof in the pudding, out of ten women who developed liver problems when they were put on an experimental choline-deficient diet, nine of them developed fatty liver and only one of them developed elevated liver enzymes (7).

Thus, the choline requirement is almost certainly more than 500 mg/day.  There are virtually no solid studies in the general population, however, that have randomized people to multiple different choline intakes and measured an important health outcome, which is what would be needed to establish a solid choline requirement. 

Once recent exception to this rule (8) showed that 1100 or 2200 mg/day of choline protected against the DNA damage that otherwise occurred in people consuming 300 or 550 mg, but this study was very small and was conducted in men who were restricted to the RDA of folate, and who thus had declining folate status through the study.  As we'll see below, the choline requirement depends on the intake of folate and a number of other nutrients.

The Choline Requirement Is Dependent on Intakes of Folate, B12, B6, and Betaine

Another reason it's almost impossible to come up with an exact amount of choline we should consume is because choline arrives at an intersection in the methylation pathway where it crosses paths with folate, vitamin B12, vitamin B6, and betaine.  Here's a simplified chart showing this pathway:

Abbreviations: SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine

As we can see from the chart, methionine is a critical amino acid used for the generation of SAM, which is in turn used for the methylation of proteins, DNA and other substances.  Methylation is critical to the regulation of gene expression and the stability of our DNA, but it's also the process that we use to make choline!  That's right, the PEMT enzyme uses SAM to make phosphatidylcholine, a choline-containing phospholipid that can later be broken down to free choline.  For more information on the PEMT enzyme, see my post, "Does Choline Deficiency Contribute to Fatty Liver in Humans?"

Whenever SAM methylates another molecule, it generates SAH and then homocysteine.  In all cells, homocysteine can be turned back into methionine to start the process all over again with the help of vitamin B12 and folate.  In the liver, when the methylation process is proceeding adequately, vitamin B6 gets rid of any extra homocysteine by turning it into cysteine.  The cysteine can then be used to make glutathione, the main antioxidant of the cell and one of the liver's principal detoxfication tools.  For more on glutathione, see my post over at WestonAPrice.Org, "The Biochemical Magic of Raw Milk and Other Raw Foods: Glutathione.

The liver and kidney can also use choline to make betaine, which can substitute for folate and B12 in the regeneration of methionine through a completely different enzymatic pathway.  Betaine is also important to regulating osmotic pressure in the kidney. 

Thus, folate, vitamin B12, B6, and betaine can spare choline, but only methionine can be used to make choline.  The B vitamins and betaine can thus fulfill choline's role in methylation, at least in the liver and kidney, but only methionine can provide the choline needed to export liver fat, to serve as a neurotransmitter, or to make our cell membranes work properly.  As I pointed out in "Does Choline Deficiency Contribute to Fatty Liver in Humans?," studies conducted thus far suggest that the vast majority of our population may have at least one not-so-effective gene for making choline from methionine. 

To make even more of a mess of this, the PEMT enzyme actually creates homocysteine in the process of creating choline!  So, if your PEMT engine is running nice and smoothly, you can make your own choline, but you still need more betaine and B vitamins to neutralize the homocysteine that's generated in the process.  If your PEMT engine is working like this, however...

... well, then, you've got another problem.  If PEMT isn't using up your methionine to make choline, the methionine is just going to go further on down that pathway shown above and make more homocysteine anyway! 

Thus, although having a PEMT gene that Uncle Buck would surely envy might lower our choline requirement, consuming lots of methionine won't help us at all.  In fact, extra methionine just gives us more homocysteine and thereby increases our need for choline, betaine, folate, B12, and B6.

As I previously pointed out in my 2007 pregnancy nutrition article, the interplay between all these nutrients as well as some other amino acids is one reason we don't want to load up on lean muscle meats.  Rather, we should balance muscle meats with skin, bones, organs, and leafy vegetables.

While extra methionine isn't such a great idea, studies clearly support an interaction between the B vitamins and choline and show that B vitamins, betaine, and choline can all substitute for each other in order to support the methylation pathway (9, 10, 11, 12, 13). Thus, whether we need to actually eat choline or just eat B vitamins and betaine instead will be largely determined by how great our PEMT enzyme works.

And this, dear friends, leads us to "The Wheat Paradox."

The Mighty Mighty Betaine and The Wheat Paradox

In the comments of "Does Choline Deficiency Contribute to Fatty Liver in Humans?" blogger and commenter Ned Kock suggested that the choline connection may be able to resolve a number of apparent paradoxes.  Indeed, it could certainly resolve contradictory findings about whether common energy stores like sugar, alcohol, and fat are bad for us, since these substances clearly increase the need for choline.  But our buddy betaine is taking a big elephant in the room for a ride, and the elephant's name is Wheat.

We are all, of course, awaiting with baited breath Denise Minger's long-anticipated wheat post, in which she will reveal some plausible mechanisms by which wheat could contribute to the risk of heart disease.  But Denise also uncovered the curious case of the Tuoli, who lived largely off wheat and dairy, but had reasonably low rates of cardiovascular and other diseases.  Likewise, the inhabitants of Crete live largely off wheat and dairy.  Although they do have some heart disease, studies in the 1960s showed that the rates were very low by Western standards, especially for a population where half the men smoked (15).

As it turns out, by far and away the the best sources of betaine (1) are wheat and spinach:

The betaine is especially abundant in the germ and bran of the wheat, but wheat is such a great source that even white bread of all things has a decent amount!  By contrast, virtually every other food has such a puny amount of betaine in it that it couldn't climb onto this chart even if the very existence of the world depended on it.

Clearly, wheat offers a major advantage to someone with a low intake of eggs and organ meats, and spinach would offer a similar benefit on a gluten-free diet.  In fact, spinach is much richer in betaine than whole wheat.

The choline connection may thus provide resolution to a number of paradoxes, including one that Ned pointed out, that the French consume plenty of white bread.  It's the red wine, the red wine, the red wine!  Perhaps.  But eating liver is likely to protect against some of the nasty effects of eating sweets, and even white bread has the surprising saving grace of providing some betaine in addition to the otherwise nutrient-depleted package of toxic junk it provides.

As pointed out above, however, we can't be quick to assume that betaine can replace choline in everyone.  As pointed out above, genetic variation in the PEMT gene will most likely make or break the success of such a replacement.

Genes and the Choline Requirement

As I pointed out in "Does Choline Deficiency Contribute to Fatty Liver in Humans?," studies conducted thus far suggest that the vast majority of people in our population may have a not-so-effective version of the PEMT gene.  Consider this graph from an American study (16):

Even among healthy controls, the prevalence of at least one "defective" version ("defective" compared to the other version) is over 80%.

Such studies (16, 17, 18) have involved anywhere from fewer than 100 people to over 3000 people, have been conducted in North Carolina and Long Island, and have represented Caucasians, African-Americans, Asians, Native Americans, and other heritages.  They have consistently shown the prevalence of at least one copy of the less effective gene in 75-88% of the population.  Nevertheless, there is likely to be considerable variation between ethnic groups, and the high prevalence probably primarily reflects the Caucasians and possibly African Americans that have been represented in these studies to greater extents than other groups.

In the comments of "Does Choline Deficiency Contribute to Fatty Liver in Humans?," Ed suggested that cultures with more plant-based and less organ meat-based diets might have higher prevalences of the more effective PEMT gene. 

There aren't many studies on this available, but there's certainly large variation between populations.  Here's the prevalence found in a recent Japanese study (19):

Whereas most Americans may have at least one copy of the less effective gene, most Japanese may have two copies of the more effective gene and none of the less effective gene.

Similar results were found in a recent Chinese study (20):

Thus, it is quite plausible that some populations have very high prevalences of the "good" version of this gene, which allows them to make their own choline from methionine for the export of liver fat, to use as a neurotransmitter, and to use in cell membranes.  Meanwhile, they could neutralize the homocysteine generated in the production of choline with high intakes of betaine, folate, and vitamins B6 and B12.

Aye! So How Much Choline Are You Saying We Need???

In conclusion, rather than declaring how much choline people need to eat, we can much better support Ned Kock's idea that the choline connection will, when viewed properly, resolve lots of apparent paradoxes.

Not everyone needs a lot of choline.  People with two copies of the awesome 'possum version of the PEMT gene may get by with very little choline but with very high intakes of B vitamins and betaine.  People with one or more of the not-so-hot version of this gene may need lots of organ meats and egg yolks to keep their liver from looking like an Eskimo's dinner. 

In America, at least, it would appear that lots of us need lots of egg yolks and liver.

Read more about Chris Masterjohn, PhD, here.