Tags: blood groups
Major news about one of my favorite molecules, l-fucose. In addition to being part of the antigenic structure of the H antigen found in blood group O, fucose is now garnering attention as an important component in learning. Although neurophysiology spends quite a bit of time looking at the neurosynaptic junction (the gap between two nerve cells, where nerve conduction occurs) most of the emphasis is on the neurotransmitters (such as serotonin and dopamine) that can jump the gap.
However, what goes into holding the synapse together may be as important a factor in cognition and learning as what jumps across the synapse. And that appears to be lectin-like receptors on one side of the nerve synapse which bind to fucose as a ligand on the other.
In other words your nerves have a sweet tooth for fucose.
Reaction in the brain involving fucose skyrocket during periods of intense learning. And human milk is a very rich source of the sugar, with amounts far higher than all other species. The sugar content of human milk varies by ABO blood type and secretor status which makes me want to do a study looking at learning differences along blood group and secretor status in breast fed and bottle fed children.
The fucosyltransferase enzymes FUT1, FUT2 and FUT3 are very intimately involved in determining ABO, secretor and Lewis blood types and recent research has linked serum B12 levels (another important player in proper nerve function) to the FUT2 (secretor) gene.
Fucose and fucosylation have a big role in ontogeny (the origin and the development of an organism from the fertilized egg to its mature form) via it's role in the development of the Lewis X antigen (FUT9) which supports cell-to-cell-adhesion in embryos. Lewis X expression in the brain is in turn controlled by the PAX6 gene, which regulates many elements of nerve growth in addition to forming the architecture of the iris.
The link between PAX6 and Lewis X (FUT9) may explain why a recent study showed that at least some aspects of personality were determined by the genetics of iris formation. Close-up pictures were taken of the study participants' irises, and they also filled out a questionnaire about their personalities. The researchers looked at crypts (pits) and contraction furrows (lines curving around the outer edge of the iris), which are formed when pupils dilate. It was found that those with more crypts were likely to be tender, warm and trusting, while those with more furrows were more likely to be neurotic, impulsive and give in to cravings.
PAX6 is gene that helps regulate embryonic differentiation. PAX6 also has some interesting effects on adrenal and pancreatic function as well as norepinephrine expression in the gut via the enteric nervous system. Maybe there's a future in medicine for the iris after all.
Going forward, I predict that soon the best thing to use in kids who are learning-challenged will not be the usual suspects like Ritalin or SSRIs, but rather glycomic agents from the diet that enhance fucosylation. These drugs do enhance the function or persistence of neurotransmitters, but fucosylation enhancers seem to enhance the stability of the entire neural network. It makes no sense to up-regulate neurotransmitters if you haven't insured that the nerves are holding to each other in the first place.
Of course, most of the old blood typers know that Bladderwrack (Fucus vesiculosis) is a decent source of fucose.
Schizophrenia, gluten, and low-carbohydrate, ketogenic diets
We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.
Previously, Dohan (Acta Psych Scand 1966, 42(2):125-152) observed a decrease in hospital admissions for schizophrenia in countries that had limited bread consumption during World War II, which suggested a possible relationship between bread and schizophrenia. Early work with lectins clearly showed that the brains of schizophrenics bind lectins differently than the brain tissue of non-schizophrenics, which appears to make sense in that the carbohydrate content of schizophrenic brain tissue (in addition to dementia and a few other illnesses) revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate; many of these blood group active carbohydrates with known lectin binding affinities (link).
Over the years some of the most stirring letters I've received from book readers have centered around improvements in family members with schizophrenia. Almost all of these letters have been from or about blood type O schizophrenics, which may mean that the nutritional approach to schizophrenia might necessarily differ by foods and blood type. We are now only beginning to understand the effects of tissue glycosylation on the development and maintenance of brain neural networks.
Diabetes Metab. 2009 Sep;35(4):262-72. Epub 2009 May 5.
Intestinal microflora and metabolic diseases.
Serino M, Luche E, Chabo C, Amar J, Burcelin R.
Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity-such as found in the intestinal microflora-and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease-to cite but a few-the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.
Increasingly, studies are showing that changes in the microflora content of the digestive tract can be linked to metabolic illnesses, including type II (adult onset) diabetes and obesity. Blood group and secretor status play an important role in conditioning the overall characteristics of the digestive tract, including influencing the appearance and frequency of many strains of bacteria.
Pathol Biol (Paris). 2008 Jul;56(5):305-9. Epub 2008 Jan 30.
Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding.
Cani PD, Delzenne NM, Amar J, Burcelin R.
A recent growing number of evidences shows that the increased prevalence of obesity and type 2 diabetes cannot be solely attributed to changes in the human genome, nutritional habits, or reduction of physical activity in our daily lives. Gut microflora may play an even more important role in maintaining human health. Recent data suggests that gut microbiota affects host nutritional metabolism with consequences on energy storage. Several mechanisms are proposed, linking events occurring in the colon and the regulation of energy metabolism. The present review discusses new findings that may explain how gut microbiota can be involved in the development of obesity and insulin resistance. Recently, studies have highlighted some key aspects of the mammalian host-gut microbial relationship. Gut microbiota could now be considered as a "microbial organ" localized within the host. Therefore, specific strategies aiming to regulate gut microbiota could be useful means to reduce the impact of high-fat feeding on the occurrence of metabolic diseases.
It has been known for quite a while that the colons of obese individuals are considerably longer than non-obese people. Now the idea is increasingly being advanced that obesity is, in part, related to greater "energy harvest." This would appear to throw the time-honored "just eat less and exercise more" argument right out the window and verify the common observance that many overweight people do not consume any greater amount of calories than many non-obese people.
J Pediatr Gastroenterol Nutr. 2009 Mar;48(3):249-56.
Intestinal microbiota during infancy and its implications for obesity.
Reinhardt C, Reigstad CS, Bäckhed F.
Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Obesity is a worldwide epidemic, threatening both industrialized and developing countries, and is accompanied by a dramatic increase in obesity-related disorders, including type 2 diabetes mellitus, hypertension, cardiovascular diseases, and nonalcoholic fatty liver disease. Recent studies have shown that the gut microbial community (microbiota) is an environmental factor that regulates obesity by increasing energy harvest from the diet and by regulating peripheral metabolism. However, there are no data on how obesogenic microbiotas are established and whether this process is determined during infancy. The sterile fetus is born into a microbial world and is immediately colonized by numerous species originating from the surrounding ecosystems, especially the maternal vaginal and fecal microflora. This initial microbiota develops into a complex ecosystem in a predictable fashion determined by internal (eg, oxygen depletion) and external (eg, mode of birth, impact of environment, diet, hospitalization, application of antibiotics) factors. We discuss how the gut microbiota regulates obesity and how environmental factors that affect the establishment of the gut microbiota during infancy may contribute to obesity later in life.
I'm going to try to develop the habit of posting about new and interesting research findings that I come across in the science literature. Where appropriate, I'll add some pithy commentary as well.
Research Bias Against Alternative Medicine
"Slowly they are beginning to report on the welcome trend of evidence based clinical trials for complementary and alternative medicine (CAM), including herbal remedies. Unfortunately, the media still rely for their sources on high quality medical journals, which are more likely to report negative results about CAM and positive results about pharmaceuticals, The clinical trials in the study showed no difference in quality between herbal remedy and pharmaceutical trials, but CAM was still reported on more skeptically".
Finally someone has the courage to address the bias against plant medicines often seen in the major media and high-profile science journals. As I have said many times before, the risks of herbal medicine are often blown way out of proportion, while the corresponding high risks of certain pharmaceuticals always seem to be "acceptable in light of their potential benefits." Every medical intervention carries risk, but when viewed against the huge number of drug reactions per year (20,000+ people die every year from NSAIDs such as Advil or Tylenol) the small number of reactions to herbal medicines (mostly allergic type reactions) appear to be over-exaggerated as part campaign of deception. Thanks to my colleague Rick Kirschner for recently mentioning this article.
Take it from me: After more than a decade of similar treatment, I know one of these campaigns when I see one.
ABO Blood Group and the Risk of Pancreatic Cancer
In two large, independent populations, ABO blood type was statistically significantly associated with the risk of pancreatic cancer. Further studies are necessary to define the mechanisms by which ABO blood type or closely linked genetic variants may influence pancreatic cancer risk.
This study was extensively publicized in the media, and while welcome as yet another link in the under-explored relationship between blood group antigens and cancer (see my 'Verisimilitude' lecture), these results have been reported in earlier studies (as well as similar results in bile duct cancer).
More interesting to me is the link between ABH secretor status and the predictability and reliability of the most common tumor marker test for pancreatic cancer. This tumor marker, called CA19-9, is variable based on ABH secretor status, yet this fact is virtually unknown in oncology.
Involvement of intestinal alkaline phosphatase with ABO and secretor blood group types
These results indicate that IAP is strongly involved in chylomicron formation and fatty acid metabolism might change among ABO blood type. In addition, ABO blood type classification in apoB-48 measurement would improve the diagnostic value in the evaluation of metabolic syndrome.
Tom Greenfield wrote about this study a few years back, but I wanted to bring it back since, like most studies of this sort, it has gone completely unnoticed by the nutrition communinty at-large. IAP is an enzyme implicated in transcellular transport of chylomicrons, large molecules that transport dietary lipids from the intestines to other locations in the body. Since 1966 it has been known that this enzyme varies among ABO blood groups and secretor status, with type O secretors having the highest amount and A non-secretors the lowest. Since IAP is critical for breaking down dietary cholesterol and enhancing the assimilation of calcium.
This calls into question the so-called 'Bone Hypothesis,' a long-treasured argument of vegans and dietitians everywhere, that dietary protein (especially from animal sources rich in the sulfur amino acids) should increase acid production in the body, and that in response to the acid load induced by a high animal protein diet, bone may be called upon to act as a reservoir of alkali using bone calcium as a buffering source.
As the theory goes, the long-term consequence of this reliance on bone to buffer the endogenous acid would be increased rates of skeletal loss and a decrease in bone mineral density. The hypothesis would also predict that a long-term, high protein diet would increase fractures.
However, in a recent study it was found that:
Studies conducted over the past 8 years in our laboratory call the traditional high protein bone hypothesis to question. We have found that a high protein diet induces high levels of urine calcium primarily because it increases intestinal calcium absorption. Second, a low protein diet acutely reduces intestinal calcium absorption, resulting in an abrupt rise in serum parathyroid hormone.
No only is IAP induced at high levels in blood group O individuals by a protein diet, one can expect it to increase bone density in these people. Not only that, evidence exists which indicates that the physical expression of the blood type A antigen appears to turn off IAP in the intestinal tract.
We found that red cells of blood group A bind almost all intestinal alkaline phosphatase; erythrocytes of blood group B or O to a much lesser degree. This is in accordance with the fact that intestinal alkaline phosphatase is found more frequently in the serum of individuals of blood group O or B than in serum of persons of blood group A.
I challenge anyone who still clings to the idea that blood groups have no scientific role in dietary personalization to respond to these basic facts.
It comes down to this simple challenge: Either put up or shut up.