"Hey buddy, wanna buy some exorphins?"

Dr. Christine Zioudrou and colleagues at the National Institutes of Mental Health got this conversation going back in 1979 with their paper, Opioid peptides derived from food proteins: The exorphins.

Exorphins are exogenously-derived peptides (i.e., short amino acid sequences obtained from outside the body) that exert morphine-like properties. Mimicking the digestive process that occurs in the gastrointestinal tract using the gastric enzyme, pepsin, and hydrochloric acid (stomach acid), Zioudrou et al isolated peptides from wheat gluten with morphine-like activity. They followed this research path because of the apparent association of wheat and mental illness.

In the bioassays used, wheat-derived exorphins competed successfully with the endogenous opiate, met-enkephalin. Interestingly, casein-derived (i.e., casein milk protein) exorphins were also identified that also displayed opiate-binding activity, though less powerfully. The morphine-like activity was also blocked by the drug, naloxone (the same stuff given to people exposed to morphine overdose).

Among the many devastating effects of celiac disease , the immune disease that develops from wheat gluten exposure, are mental and emotional effects, such as anxiety, fatigue, mental "fog," depression, bipolar illness, and schizophrenia, that disappear with removal of gluten. Many parents of autistic children also advocate wheat-free diets for similar reasons.

Among the many wonderful comments posted on the last Heart Scan Blog post, "I can't do it," was Anne's:

I am not the Anne in your post, but I was addicted to wheat. It was my favorite food. I lived on and for breads. Then I discovered I was gluten sensitive and I did go through a withdrawal of about 4 days. After 4 days I noticed my health problems were disappearing. Depression, brain fog and joint pain are 3 of the many symptoms that disappeared. That was 6 yrs ago.

Tell Anne that I had dreams about bread in the beginning - they will pass. Now the donuts, breads, cookies and cakes in the stores and at work don't even look good. In fact, I don't like the smell of bread anymore. It takes time, but the cravings do pass.

Combine wheat"s exorphin-driven addictive potential with its flagrant blood sugar-increasing properties, and you have a formula that:

1) makes you fat
2) increases likelihood of diabetes, and
3) makes you want to keep on doing it.

Reminds me of nicotine.

My personal view: I have absolutely no remaining doubt that wheat products have no place in the human diet. Not only does the research provide a plausible basis for its adverse health effects, but having asked hundreds of people to remove it from their habits has yielded consistent and remarkable health benefits. Just read the reader comments here and here.

Comments (18) -

  • Anonymous

    5/31/2009 4:49:20 PM |

    Sometimes I get confused when people say "wheat". Do you think this also applies to other grains? What about rice and oats?


  • Anonymous

    5/31/2009 9:10:11 PM |

    Received so much valuable advice from Dr Davis blog(Vit D,Fish Oil, Thyroid,Niacin) that even though I love wheat(the thicker the crust on anything the better)That I decided to trust him on this one too. I had 10 days of misery ie:no energy,grumpy,and hungry. My wife said bad words about Dr D.... threatened to force feed me donuts because I was so nasty tempered. Now 2 months later I dropped the 15 lbs I needed to, feel better and have found it easy to stay off the stuff. Thanks Dr Davis (my wife says she is sorry!)

  • Neonomide

    5/31/2009 11:21:57 PM |

    Or rye, perhaps?

  • Materialguy

    6/1/2009 2:23:18 AM |

    I was listening to a CD version of the book "1491". It talked about the uniquely Native American ("Indian") invention of agriculture combining maze (corn) and squash and other beans. This provides all the essential amino acids.

    It somewhat paralleled the Western invention of agriculture based on wheat and other grains(barley, oats,...).

    The comment of significance was that the Native Americans were considerably taller than the newcoming European settlers.

    I wonder if that is a "wheat thing" as well.

    I read not long ago that when Lafayette and the French soldiers joined forces with the new Americans during the Revolutionary war, it was noted that the new Americans were also taller than the French soldiers.

    I wonder.

  • kris

    6/1/2009 2:47:33 AM |

    Although i have reduced my wheat intake by 90% now, but it is not always easy to follow this diet. specially when you also have to avoid few other grains because of the hypothyroid issue. even though it has been said that iodine sufficiency shouldn't let goiter foods do any harm but, i can still feel the effects of these foods with in minutes after consuming, cooked or uncooked.
    Few years ago i had bloody stomach every time i went to the bathroom. tired of doctors wait game and suggested operation date 3.5 months away, that's when i decided to become my own doctor and basically started studying my self. i was lucky that with in 3 days i was able to stop the bleeding with simple usage of Aloe (not the regular aloe it is high dose of Aloe Mucilaginous Polysaccharides) and manuka honey. but i learned later on that, all of this started with hypothyroid. while studying this stomach issue i went through this made sense notes from this alternative mental health site.
    where the author talked about oxidative stress and said,
    "factor to consider is the high incidence of oxidative stress in the G.I. tract. This environment can destroy key digestive enzymes such as DPP-IV (needed to break down casein & gluten)..... This condition is especially common in autism-spectrum disorders. Failure to correct the oxidative stress would doom supplemented enzymes to an early death. The result can be similar to Pickett's Charge at the battle of Gettysburg.... The digestive enzymes are mowed down as soon as they enter the G.I. tract. The casein-free, gluten-free diet often results in rapid striking improvements. However, nutritional supplements which overcome G.I. tract oxidative stress can make the CF/GF diet unnecessary.
    Normalization of zinc, metallothionein, and glutathione in the G.I. tract isn't difficult to accomplish. It's a lot easier to take a couple of capsules daily than this difficult diet. It takes about 6-8 weeks for the G.I. tract to get "fixed" using this therapy.
    We've had many patients who were extremely sensitive to dairy and wheat.... and did marvelously after the CF/GF diet. Many of these same patients completely lost their sensitivity to casein and gluten after the antioxidant supplementation..... and now can eat a normal diet without a problem".
    the reason that i am bringing this discussion that i have seen people in certain communities where wheat is their at least 40% of the total diet. yet some individuals in that same community are still got no wheat belly and no major health issues what so ever.

  • Andrew

    6/1/2009 5:35:55 AM |

    "Mental fog" seems very ambiguous.  Is there any kind of scientific data or quantifiable means by which one can measure the effect of wheat on "brain fog?"

    Any studies, or is it all anecdotal evidence?

  • Anonymous

    6/1/2009 11:20:52 AM |

    Please read about the Specific Carbohydrate Diet and the book "Gut and Psychology Syndrome" by Natasha Campbell McBride. Very interesting and nothing we learned in medical school.

  • Lena

    6/1/2009 11:22:41 AM |

    There are some who propose that we shouldn't eat any grains at all, because all grains have some particular proteins (particularly defence peptides) which provide protection to the grain plant, but which are harmful to the human immune system. This includes rice, corn, maize, etc.

    Check out this article: "Cereal Grains - Humanity's double-edges sword" http://www.thepaleodiet.com/articles/Cereal%20article.pdf

  • Nameless

    6/1/2009 5:11:06 PM |

    Although I don't doubt the health benefits of eliminating wheat, I am interested in how the Mediterranean diet is considered healthy, yet includes pasta.

    Fruits/veggies/grapes mitigate the damage wheat does, or is there some other mechanism? Perhaps genetics play a role, where certain individuals have a much bigger problem with wheat (as to heart disease) than others?

  • Anonymous

    6/2/2009 1:46:35 AM |

    Wheat is the enemy. Ah well....that explains the Italians; and for that matter, the French.  But wait, they are, on average, more healthy than Americans,...... So what about those Japanese and other Asian cultures who consume vast amounts of Omega 6 from soy....maybe their delta-6 desaturase is higher than the average American, and maybe, just maybe they have more exercise in their daily routine.

  • Anonymous

    6/2/2009 1:35:34 PM |

    Dear anonymous, it is a myth that Asians eat vast amounts of soy. They actually eat very little each day. Our food manufacturers have sold us that bill of goods so that we will buy products (franken-foods) with "healthy soy" which is actually the waste product of the soy oil industry--yet another bad for you food.

  • Anna

    6/5/2009 2:58:00 PM |

    No disrespect to the French and the Italians - I love to visit both countries and know many natives - but the French and Italians are just "less sick" than we are, they aren't necessarily good examples of abundant health, esp the Italians.  They don't eat as much pasta as we are led to think, but wow, they do eat a lot of bread and sugar.  I saw lots of signs of diabetes among the locals when I was in Italy last summer.  

    Overall, my impression from my visits to friends and family of my husband's (for nearly 15 years) is that Europe seems to be heading down a similar  sorry path we've already trodden; they are just a few years behind behind us.  Some European countries are following at a slower pace or a slightly different route, but the signs are there that the industrial food culture is permeating and doing damage, esp in the younger generations.  I think it's happening in industrial parts of Asia, too.

    Celiac disease research is very active in Italy because  of the high rate of celiac incidence there.  Check Pub Med, you'll see a high number of Italian papers.

  • Anonymous

    6/11/2009 3:20:44 AM |

    You have more personal experience than I do from visits and I respect you observations.  I have not been to either country for over 10 years.

    Take a look at the stats on Nationmaster:-


    Italy and France are low on the list for heart disease deaths.

    Also on Nationmaster you can find stats for a whole host of other things EG wine consumption..... France and Italy top this list. On soft drink consumption, they are at the bottom. Obesity stats also show them at the bottom and USA is #1 but USA is not #1 for heart disease deaths, it is in the mid tier.

  • George D. Henderson

    5/19/2010 10:56:38 PM |

    In my copy of Lao-Tzu's Te Tao Ching, which was found in a Chinese Han era tomb dated 168BC, it states that one of the other documents found in the tomb was a treatise on "the health benefits of grain avoidance".

    Pasta is made from Durhum wheat which has a slightly different genetic profile from baker's wheat.
    Even a single amino acid difference in a gluten or casien sequence can change the way it breaks under pepsin digestion, altering or blocking the production of any given exorphin. In my experience the Durhum gluten exorphin is not as vicious as the baker's wheat gluten exorphin, but it is still nasty.
    This is paralleled in milk chemistry - beta-casien from A2 milk has a proline residue where beta-casien from A1 milk has a histidine residue; this means that A1 milk forms the potent exorphin beta-casomorphin 7 in amounts approximately 100x that of A2 milk. A1 and A2 are genotypes of common milk bearing cows. Many people who cannot tolerate A1 milk (normal cows milk) can tolerate A2 cow's milk, or goat's milk, which has A2 properties. (Milk can create other exorphins, but BCM-7 is especially potent and well-researched)
    This is all linked to the use of low-dose naltrexone to stimulate and harmonise immunity by elevating endorphin levels. LDN can be seen as a drug that undoes the harmful effects of exorphins.
    Also, large amounts of digestive protease enzymes are heavily relied on by many alternative canmcer therapists (as is LDN); these will tend to digest exorphins before they enter the bloodstream. This is not the actual rationale for enzyme-based cancer therapy, but to my mind it makes far more sense than the out-dated traditional explanation (the Beard hypothesis). Use of morphine after cancer surgery is associated with a significantly lower rate of remission - morphine is the classical exorphin.
    The exorphins only enter the blood if two conditions are met - inadequate pancreatic digestive enzymes (proteases), and/or excessive intestinal permeability (or stomach ulcer) - "leaky gut" (because exorphins, like classic opiates, act directly on the gut, a lack of pancreatic enzymes can eventually lead to leaky gut. Aspirin abuse (even 1 a day, which has increased the rate of Crohn's disease five-fold in a population study - I use ginkgo or reishi instead), antibiotics, and many other drugs can contribute to leaky gut. Probiotics and good nutrition (adequate protein annd fats) are protective against it.

  • George D. Henderson

    5/19/2010 11:11:02 PM |

    Andrew, there are scientific studies online done on rats in mazes that show orally administered gluten exorphins affect standard tests of learning, memory, etc (mazes and the like) without affecting "swim time" or other more physical parameters. That equates to "brain fog" (cognitive impairment) in humans, I reckon. This is one of the 15 references on PubMed:

    [Delayed effect of exorphins on learning of albino rat pups]
    [Article in Russian]

    Dubynin VA, Malinovskaia IV, Beliaeva IuA, Stovolosov IS, Bespalova ZhD, Andreeva LA, KamenskiÄ­ AA, Miasoedov NF.

    The delayed effect of food-derived opioid peptides (exorphins) after chronic administration on postnatal days 1-14 on the learning of albino rat pups has been studied. Heptapeptide YPFPGPI (beta-casomorphin-7), pentapeptide YPLDL (rubiscolin-5) and pentapeptide YPISL (exorphin C) improved the development of the conditioned foraging reflex in a complex maze. Hexapeptide PFPGPI lacking the N-terminal tyrosine proved inefficient. Only beta-casomorphin-7 had an effect (negative) on passive avoidance conditioning. The obtained data confirm that exorphins (particularly, milk-derived beta-casomorphins) can have significant and long-term effects on the environmental adaptation of young mammals.

  • buy jeans

    11/3/2010 8:42:48 PM |

    Among the many devastating effects of celiac disease , the immune disease that develops from wheat gluten exposure, are mental and emotional effects, such as anxiety, fatigue, mental "fog," depression, bipolar illness, and schizophrenia, that disappear with removal of gluten. Many parents of autistic children also advocate wheat-free diets for similar reasons.

  • Physical Therapy Supplies

    4/28/2011 5:43:24 AM |

    Good post! I respect you observations. Pasta is made from Durhum wheat which has a slightly different genetic profile from baker's wheat. I am interested in how the Mediterranean diet is considered healthy, yet includes pasta.
    Boxing/MMA Supplies

  • Ruth

    3/4/2013 3:22:48 PM |

    While the term "mental fog" is really vague and unscientific, thinking in more specific terms one can see that , yes it is well documented.  The protein in wheat gluten is very difficult to digest, and in the case of certain autistics, schizophrenics, celiacs, people with wheat gluten enteropathy etc. it is not completely broken down, forming long chains of peptides that have a chemical composition similar to opiates.  These people are all known for their resistance to dietary change and extreme addiction to wheat gluten and often dairy, the protein of which has a chemical composition similar to that of wheat gluten and therefore, is also may form similar peptides.  The symptoms such individuals display might be described in similar terms, dazed, spaced out, the appearance of opium addicts, or "mental fog."  There is research on this phenomenon.