Fibromyalgia: It's the food, again! (probably).

From http://stickmancommunications.co.uk/Keyring-Card-Fibromyalgia

Serendipity strikes again! On Facebook, I saw https://www.facebook.com/PaleoDietNewZealand/posts/763653980371516 . That linked to Fibromyalgia and non‑celiac gluten sensitivity: a description with remission of fibromyalgia.

For people unfamiliar with scientific terms, here are some definitions:-
Non-celiac gluten sensitivity: A reaction to gluten, not due to Celiac (Coeliac in the U.K.) Disease.
Remission: (medicine) An abatement or lessening of the manifestations of a disease.

So, is Gliadorphin-7 (formed during the digestion of gluten) to blame?

Probably.

Could Beta CasoMorphin-7 (formed during the digestion of A1 cow's milk) also be a problem?

Possibly.

Is Increased/Excessive Intestinal Permeability allowing the above large molecules to pass through insufficiently tight junctions?

Definitely, maybe.

Is there really no cure for Fibromyalgia? It's possible to tighten-up insufficiently tight junctions. Insufficiently tight junctions can be caused by:-

1. Insufficient sun exposure, causing hypovitaminosis D. See http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Vitamin+D%22[All+Fields]+AND+%22tight%20junction%22+AND+hasabstract[text]

2. Excessive consumption of oils high in polyunsaturated fatty acids. See Dietary Fat Can Modulate Intestinal Tight Junction Integrity.

3. Excessive consumption of Wheat. See http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Wheat%22[All%20Fields]%20AND%20%22tight%20junction%22[All%20Fields]%20AND%20hasabstract[text]%20AND%20%22humans%22[MeSH%20Terms]

4. Excessive exercise. See Shedding Some Light on the Leaky Gut <> Exercise Connection. Plus: 20+ Things You Should or Shouldn't Do to Protect and Restore the Integrity of Your Intestinal Wall.

5. Lack of dietary Sulphur. See Sulphation and Autism: What are the links? A good source of sulphate is Epsom Salts.

See also Physiology and Immunology of Digestion.

And finally...
If a science person ever tells you "Increased/Excessive Intestinal Permeability a.k.a. "Leaky gut" just doesn't exist because, you know, I'm a scientist.", point out that it's an Appeal from authority fallacy, and demand that they provide high quality evidence to support their statement.

Because, you know, I'm a retired Electronic Engineer! :-)

Wheat, Constipation, Ischaemic Heart Disease, Type 1 Diabetes, Schizophrenia and Autism.

Did you see this coming?

Gliadorphin 7, from http://en.wikipedia.org/wiki/Gliadorphin

The above 7-peptide chain contains 3 molecules of proline (the pentagon with a "N" at one corner), just like:-

Bovine β-casomorphin 7, from http://en.wikipedia.org/wiki/Casomorphin

From Further research for consideration in 'the A2 milk case'.
"Prior to discussion it must be clarified that the hypothetical link between A1 consumption with autistic spectral disorder (ASD) and schizophrenia relates not to the cause of the condition but to the aggravation of symptoms associated with these neurological conditions. More specifically, the hypothesis states that the absorption of food-derived exomorphins such as beta casomorphin 7 (BCM 7) may aggravate symptoms associated with ASD or schizophrenia.

This hypothesis is the basis of 'dietary intervention' that excludes gluten and casein (Knivsberg et al., 2002) from the diet of ASD patients. The former, gluten, has been shown to release gliadamorphin, an exomorphin comparable in opioid activity to BCM-7. A number of laboratories in the United States and Europe offer urine tests, which determine the level of peptides including BCM 7 and other beta casomorphins to serve as an indication of the potential usefulness of dietary intervention in the treatment of ASD patients. One published study reports that a casein- and gluten-free diet was accompanied by improvement in 81% of autistic children within 3 months (Cade et al., 2000)."


According to What is gliadorphin?
"What is gliadorphin? Gliadorphin (also called alpha-gliadin or gluteomorphin) is a substance that resembles morphine. Ordinarily, this is a short-lived by-product from the digestion of gluten molecules (found in wheat, barley, rye, oats, and several other grains). Gliadorphin is very similar to casomorphin. Gliadorphin has been verified by mass spectrometry techniques to be present in unusual quantities in urine samples of children with autism, and are believed by many to be a central part of the system of causes and effects that cause autistic development. The most probable reasons for the presence of these molecules are:
* One or more errors in the breakdown (digestion) process caused by enzyme deficiency and/or
* Abnormal permeability of the gut wall (that would allow these relatively large molecules to enter the bloodstream from the intestine in abnormal quantities)."

Continued on Rheumatoid Arthritis: It's the food!

Historical perspectives on the impact of n-3 and n-6 nutrients on health, by Bill Lands.

Here's Fig. 1. from http://www.sciencedirect.com/science/article/pii/S0163782714000253

Relating tissue HUFA balance with blood cholesterol and heart attacks. Results from the 25-year follow-up in the Seven Countries Study [35] were discussed in an earlier review [10] which noted that “Food energy imbalances which elevate blood cholesterol may be fatal only to the degree that omega-6 (n-6) exceeds omega-3 (n-3) in tissue HUFA. Such evidence raises questions about the hypothesis that blood cholesterol levels cause CHD.” Northern Europe and Southern Europe have abbreviations “No.” and “So.”, respectively. The Figure is reprinted with permission of the publisher.

Hat-tip to Dr. Thomas Dayspring for Tweeting this review.

Fig. 1 is interesting, as it shows a significant association between 25-year CHD mortality and Serum Total Cholesterol for every region except Japan. What's different about Japan, compared to Northern Europe, USA, Serbia, Southern Europe & Crete?

According to Measuring Blood Fatty Acids as a Surrogate Indicator for Coronary Heart Disease Risk in Population Studies , Philippines & Iceland have lower % linoleic acid than Japan. Where's the CHD vs TC data?

Could another difference be that the Japanese eat rice, a relatively intact grain, instead of foods made from wheat grain dust (i.e. flour) as their main source of dietary carbohydrates?

See also Using 3–6 differences in essential fatty acids rather than 3/6 ratios gives useful food balance scores , and Omega 3-6 Balance Score.

Things that make you go "Struth!"

I was wading through my Facebook News Feed when I spotted THIS. That article led me to New approach to coeliac testing identifies more Australians at risk, which in turn led me to A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways (provisional pdf), where I saw: "HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts."
HLA-DQ2.5, DQ8 & DQ2.2 are the alleles for Coeliac/Celiac Disease (CD).

Image from http://www.clker.com/clipart-tango-face-surprise.html

"Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLADQ2.5, DQ8, or DQ2.2."
There were abnormalities in ~5% of Australian women & ~7% of Australian men, even in those who didn't carry CD alleles.

"...but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men."
~1.6% of Australian women & ~1.3% of Australian men have CD.

From the discussion: "The concept of a ‘celiac iceberg’ has been important in drawing attention to a large, unrecognized group of patients with CD who do report symptoms considered ‘typical’ of CD [29]. Investigators have proposed expansion of the ‘iceberg’ to encompass patients who are genetically susceptible to CD, but show only raised IEL counts or an isolated abnormal CDspecific serology and normal intestinal histology [30-32]. Consequently, there is considerable uncertainty regarding the true extent of gluten-mediated disease in the community.

Random thoughts: About 1 in 20 Australian women & about 1 in 15 Australian men have some kind of a gut problem (IBS?) due to gliadin, even in those who don't carry CD alleles. The following made me smile.
"Making a diagnosis based on a blood test alone or commencing a gluten-free diet without a confirmatory bowel biopsy is inappropriate and can impose an unnecessary and lifelong treatment."
'Cos life without wheat, rye, barley & oats is such an imposition (undue burden) and everyone just loves to be given a bowel biopsy. <- sarcasm alert.

From Ancestry of Australian population: "More than 92 percent of all Australians descend from Europeans. Anglo-Celtic Australians (English, Scottish, Welsh, Cornish or Irish ancestral origin) make up 74 percent of the Australian population."
Most Australians have genes that originate from Britain & Europe. Uh-oh!

Why do only a small percentage of people carrying the CD allele go on to develop CD? I believe that it's down to luck. During digestion, gliadins are snipped into fragments & amino acids by the peptidase enzymes pepsin, trypsin & chymotrypsin. Gliadin fragments that contain the wrong triplet of amino acids and that manage to slip through excessively-loose tight junctions may trigger CD. Once the "damage is done", it only takes a tiny amount of gliadin to provoke an immune response.

Grains & soyabeans: more bad news.

Jamie Scott (THAT PALEO GUY) has been doing some digging and found more dirt on...

From http://commons.wikimedia.org/wiki/File:Various_grains.jpg

See Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4.
"We identify the α-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4-MD2-CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients' biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders."

See Impact of antinutritional factors in food proteins on the digestibility of protein and the bioavailability of amino acids and on protein quality.
"Examples of naturally occurring antinutritional factors include glucosinolates in mustard and canola protein products, trypsin inhibitors and haemagglutinins in legumes, tannins in legumes and cereals, gossypol in cottonseed protein products, and uricogenic nucleobases in yeast protein products."

"Among common food and feed protein products, soyabeans are the most concentrated source of trypsin inhibitors. The presence of high levels of dietary trypsin inhibitors from soyabeans, kidney beans or other grain legumes have been reported to cause substantial reductions in protein and amino acid digestibility (up to 50 %) and protein quality (up to 100 %) in rats and/or pigs."

"Normally encountered levels of phytates in cereals and legumes can reduce protein and amino acid digestibility by up to 10 %. D-amino acids and LAL formed during alkaline/heat treatment of lactalbumin, casein, soya protein or wheat protein are poorly digestible (less than 40 %), and their presence can reduce protein digestibility by up to 28 % in rats and pigs, and can cause a drastic reduction (100 %) in protein quality, as measured by rat growth methods. The adverse effects of antinutritional factors on protein digestibility and protein quality have been reported to be more pronounced in elderly rats (20-months old) compared to young (5-weeks old) rats, suggesting the use of old rats as a model for assessing the protein digestibility of products intended for the elderly."

I eat grains, also peas, beans & lentils, but not as a dietary staple. I make sure that they're thoroughly cooked at 100°C.