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Natural Medicine Articles

Exorphins, Food Cravings, and Schizophrenia

by Eric Yarnell, ND, RH © 2003

Handling food cravings when dealing with weight loss and food allergies can be a major problem. Some people trying to lose weight feel they simply cannot stop eating certain foods, even though they know they are likely contributing to obesity. A similar story is often heard from people who find out they have an allergy to a food: "But I love that food! I could never give it up."

Many people have theorized that this inability to give up harmful foods is the result of an emotional attachment to the foods. While this theory may hold merit, there is also a different aspect of food cravings that does not have to do with childhood emotional trauma.

What are Exorphins?

It has been demonstrated that certain food proteins can be broken down into what are known as exorphins, at least in the laboratory.1 Exorphins are small protein fragments (or peptides) that have an action like morphine and come from outside the body. Human nerve cells normally make their own compounds of a similar nature, but these are called endorphins because they come from inside the body.

Exorphins, endorphins, and morphine all work by way of opioid receptors. These are molecules found on many different types of cells throughout the body, but particularly smooth muscles in the intestines and on nerves. When a compound binds to and activates these receptors, all sorts of biochemical processes can result. In the brain, a sense of euphoria, happiness, and sleepiness tends to be activated, as well as reduction in pain sensation. Heroin provides an extreme example as it is one of the strongest chemicals that binds to opioid receptors. Endorphins are the body's own way of producing these same effects, though more mildly. Heroin, morphine, and other strong opioid receptor agonists (meaning chemicals that bind and activate a receptor) also induce addiction.

Exorphins: Food Heroin?

Imagine what would happen if a food were consumed that contains low-level heroin-like compounds (exorphins). Assuming that these compounds could be absorbed and reach the brain (which they have in fact been shown to do, at least in animal studies2), they could induce a mild euphoria, dull pain sensation slightly, and have a low-grade tendency to cause addiction. This sounds eerily like people's descriptions of foods they crave: "I feels relaxed and calm when I eat it." "My emotional pain seems far away." "I tried to give it up but I just couldn't." Imagine what would happen if the food exorphins were as strong as heroin, which some test tube studies suggest they can be.3

It is fairly well established that the brain's own opioid compounds (endophins) are important in how humans perceive rewards. In particular, endorphins are raised when we eat foods that are considered highly palatable.4 Thus, when humans or animals are fed delicious foods (particularly sweet and fatty ones like chocolate), brain endorphin levels go up. This may be why eating chocolate is so nice. However, it is also possible that foods that contain exorphins can get involved in our normal sensations of pleasure. Thus, instead of our own natural endorphins telling us something is tasty and to eat more of it, the food's exorphins might get involved and tell us the food was tasty.

Researchers have not yet to show that food exorphins have effects in human beings, though milk-derived exorphins have been found in the nervous systems of women who recently gave birth and in human newborns.5 One study found that casomorphins, which are exorphins derived from milk proteins (casein), can reduce pain in rats.6 This effect was blocked by a drug known as naltrexone (ReVia®), which blocks chemicals of all kinds from binding to opioid receptors in the brain. More on naltrexone later.

Another series of studies found that exorphins could act like hormones, in particular thyrotropin-releasing hormone (TRH).7 This is the neurotransmitter the brain makes that tells another part of the brain to tell the thyroid to make and secrete thyroid hormones. A complicated system no doubt, but necessary for precise control of the extremely important thyroid hormones. If compounds from food were found to interfere with this system in human studies, it could have profound implications in terms of weight management and food cravings.

Exorphins and Schizophrenia

An even more serious potential problem with exorphins relates to the mental disorder known as schizophrenia. This is a condition in which thinking is unclear and the person has hallucinations. It should not be confused with the less common multiple personality disorder, in which a person literally has different personae.

Numerous studies have shown that many people with schizophrenia improve if they stop eating wheat, and worsen if given wheat or gluten.89 Dairy products also seem to be a major problem with some people with schizophrenia. Wheat and dairy are the two foods believed to be major sources of exorphins. While it is possible that the problem is an allergic reaction, exorphin-related problems cannot be ruled out until further study is conducted.

Countering Exorphins

Because research has yet to prove the theory that food exorphins are at least partially to blame for food cravings, it is difficult to make treatment decisions. Nevertheless, there are obviously many people who have tried everything else they can think of to break food addictions and cravings, but have failed. In these cases, it may be justifiable to attempt to deal with exorphins on an experimental basis. Since not all foods contain exorphins, these solutions would not be expected to work in all situations. The foods most clearly known to contain exorphins are dairy products and grains.

One strategy is to take digestive enzymes with meals in an effort to break the exorphins down more completely into amino acids. Unfortunately, many common exorphins appear to be highly resistant to breakdown by pancreatic enzymes.10 Nevertheless, people with poor digestion should consider supplementing digestive enzymes just in case. Taking bitter herbs such as dandelion (Taraxacum officinale) leaf or yellow dock (Rumex crispus) root is a natural way to stimulate the body's own digestive enzymes and hydrochloric acid. It is unknown how effective bitter herbs are compared to enzyme supplements, because no one has ever compared them in a study.

Another potential way to counter exorphins is to take probiotics. These are supplements that contain the beneficial bacteria that belong in the colon. It has been suggested by some studies that bacteria in the gut may be partially responsible for digesting food proteins into exorphins.11 The goal is to replace potentially harmful gut flora that are producing exorphins with helpful flora that do not. This is a highly theoretical approach, but probiotics have so many other benefits with no adverse effects there is little reason not to try it. Note that variability in normal gut bacteria between individuals may, in part, explain why some people have a problem with exorphins and some don't.

It can also be wise to try a rotation diet. In a rotation diet, the craved food or foods are avoided on a regular schedule, usually being eaten only once every four days. The idea is to give the body time to compensate for each dose of the exorphins, rather than constantly piling them on. Eventually (often over many months), the time between eating the food is lengthened, until the person becomes less and less dependent. This is most successful if a health care professional is available to offer support. For people with excellent will power, the implicated foods (particularly wheat and dairy) should be absolutely avoided for 6-12 months to see what effects result.

In the case of people with schizophrenia, it is imperative that they try avoiding wheat and dairy at the least. It might be best to test (by whatever means are preferred) for all food allergens with each individual and avoid those as well. This is both because the problem could be allergies and because other foods besides wheat and dairy might be a source of problematic exorphins.

In the most extreme cases, when nothing else has worked, there are two drugs that might be useful. Naltrexone (ReVia®) and its more familiar cousin naloxone (Narcan®) are often used to treat overdoses of heroin or morphine and to help people break their addictions to these drugs. They work by blocking chemicals from binding to opioid receptors. As mentioned, one rat study found that naltrexone could block the pain-relieving effects of exorphins, as would be expected. Human studies have shown that use of these drugs will stop weight gain in many obese people, although they will not cause weight loss.12 This appears to be because the drugs interfere with endrophins' ability to cause sensations of reward after eating, thus reducing food intake somewhat. It is theoretically possibly that these drugs might help break food addictions by interfering with exorphins as well, though this has not been studied.

There could be withdrawal symptoms using these drugs unless exorphin-rich foods are avoided. Once the drugs were stopped and the exorphins were no longer opposed, symptoms could theoretically be exacerbated. These drugs are only available by prescription, and this should be considered a last ditch effort, not something to try lightly. Progress should be closely monitored by a health care professional if these drugs, which can have serious toxic effects, are used. Clearly eating less food (and healthier food) and exercising more regularly are still necessary in anyone who wishes to lose weight and keep it off--drugs are no short cut.

As an aside, Asian ginseng (Panax ginseng) root extracts have been shown to interfere with morphine in animal studies.13 It is unknown if Asian ginseng would be helpful in breaking food addictions, but its long history of use to overcome the effects of stress as well as supporting the immune system makes it even more attractive. Asian ginseng is generally harmless so it might be worth a try--however, only organically grown products should be used because Asian ginseng is threatened in the wild due to over harvesting.

Potential Benefits of Exorphins

Not all exorphins are alike, and not all of them are necessarily harmful. Everyone knows that foods can be emotionally and physically comforting. Knowing that exorphins might be causing these effects, the comforting aspects of foods can potentially be utilized. For example, if someone has just had major surgery, it might be a good time to eat wheat for the sake of reducing pain. There is always a risk of a food allergy developing though. It should also be pointed out that exorphins in breast milk may be part of why infants like it so much.

Similarly, as suggested above, some exorphins may have hormonal effects. In particular, they might actually stimulate the thyroid. Perhaps this partially explains why some people are able to eat a lot and not gain weight while others can't--the thin individuals' thyroids react more strongly to exorphins. This intriguing theory has never been tested, so it is unknown if it is true, but it offers just one more avenue for research into exorphins.

The state of research into effects of exorphins on humans is very limited. This is unfortunate given the supportive preclinical research in the field, and the potential harm that exorphins might be causing. Until this research can be done, the efficacy of therapies directed against exorphins will remain unknown. Nevertheless, it is possible that exorphins could be a significant, largely overlooked factor in problems ranging from apparent food allergies, food cravings, obesity, schizophrenia, and other conditions.

References

  1. Zioudrou C, Streaty RA, Klee WA. Opioid peptides derived from food proteins: The exoprhins. J Biol Chem 1979;254:2446-9.
  2. Hemmings WA. The entry into the brain of large molecules derived from dietary protein. Proc R Soc London B 1978;200:175-92.
  3. Zioudrou C, Streaty RA, Klee WA. Opioid peptides derived from food proteins: The exoprhins. J Biol Chem 1979;254:2446-9.
  4. Mercer ME, Holder MD. Food cravings, endogenous opioid peptides, and food intake: A review. Appetite 1997;29:325-52.
  5. Teschemacher H, Koch G, Brantl V. Milk protein-derived opioid receptor ligands. Biopolymers 1997;43:99-117.
  6. Brantl V, Teschemacher H, Blasig J, et al. Opioid activities of beta-casomorphins. Life Sci 1981;28:1903-9.
  7. Morley JE. Food peptides: A new class of hormones? JAMA 1982;247:2379-80.
  8. Storms LH, Clopton JM, Wright C. Effects of gluten on schizophrenics. Arch Gen Psychiatry 1982;39:323-7.
  9. Dohan FC, Grasberger JC. Relapsed schizophrenics: Earlier discharge from hospital after cereal-free milk-free diet. Am J Psychiatry 1973;130:685-8.
  10. Henschen A, Lottspeich F, Brantl V, Teschemacher H. Novel opioid peptides derived from casein (beta-casomorphins). II. Structure of active components from bovine casein peptone. Hoppe-Seyler's Z Physiol Chem 1979;360:1217-24.
  11. Gardner MLG. Production of pharmacologically active peptides from foods in the gut. In: Hunter JO, Jones VA. Food and the Gut. London: Bailliere Tindall:1985:121-34 [review].
  12. Mercer ME, Holder MD. Food cravings, endogenous opioid peptides, and food intake: A review. Appetite 1997;29:325-52.
  13. Kim HS, Jang CG, Lee MK. Antinarcotic effects of the standardized ginseng extract G115 on morphine. Planta Med 1990;56:158-63.
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