I received an interesting question from my Facebook Page.
Thanks for providing an awesome guide in the Genotype Diet. Been practicing it as best I can for about 7 months and feel powerful. (I'm also doing good vitamins which is definitely part of the reason I feel really good.)
When I talk to people about the Genotype Diet and the benefits I've achieved from it, the main question I get is: Exactly what research has determined the genotypes, and the superfoods/toxic foods in the book? I can't begin to answer that question as I don't recall seeing it addressed in the book or on the website.
I'd love to learn more about the types of tests that you did to determine which people are in what genotypes as well as which foods are in which categories, per type.
This is a great question, but given that the best 'scientific answer' would be to show you the data tables and computer source code I can only try to explain a bit of the process. The problem with mass-market books is that you can only provide the upper-most level of information and a simplified version of that to boot, so I understand.
What I term the 'genotypes' (really 'epigenotypes' or 'morphotypes' but try to get a publisher to agree to use these words) are semi-synthetic constructs involving a stepwise statistical analysis of variation. They stem from the phenotypic (real world) characterizations reported for the ABO groups, Rh, secretor and additional biometric markers (D2-D4, fingerprints, etc). The idea was to look for pleiotropic (sympathetic) relationships between the multi-dimensional genotype/ phenotype data, especially if they are known to exert their effects through transgenerational actions. Using multivariate analysis we then look to see how the data separates or groups together. Since, with the exception of secretor, taster, Rh and ABO, we're looking at phenotype, I felt very comfortable including data from other, traditional typing systems (Ayurveda, TCM) which were also based of physical traits.
The base data includes virtually all published scientific tabular data on variations in physiology and pathology associated with these parameters, in addition to our own profiles of roughly 3,000+ additional people. At that point the data was filtered according to degrees of three basic metabolic 'biases': 'thriftiness' (metabolic compromise), 'receptorism' (immune tolerance) and 'reactance' (auto-immunity).
The genotypes are not 'perfect' typologies (every Explorer does not look or act exactly as every other Explorer) because we cannot possibly encapsulate all variation in everybody. Two families using the same set of blueprints will most likely build two different houses, due to differing financial constraints, choice of land plot, etc. Most of the time and given the tools we might encapsulate 30-50 percent of the data variation (principal components) in any one person and what we encapsulate in one might be slightly different than what we get for another. In statistical terms this is called 'multiple inclusion criteria' and it is a keynote of factor analysis or 'fuzzy logic.'
What results are six basic 'types' that with considerable tweaking encapsulate an acceptable amount of variation. Crunching the system into six types and cramming them into a hard-coded 'book' is much less effective than dynamically generating one-to-one diets in software, but it is still a pretty good approximation of some basic phenotypic variation and is more helpful than not.
Once we get here, the next step was to match the expected physical manifestations to a large database of foods that I've been collecting for the last two decades. For each food, this database contains about 300 individual values (gluten content, vitamin A, known allergen, etc.) At this point a second set of algorithms takes over and each food is evaluated constituent-wise based on a weighed value system much like a lawyer might argue a case in court. For example, evidence of developmental instability or constrained growth (differences between left/right sides of body, certain fingerprints, short leg length) might result in limiting foods that cause excess glycation.
If no negative attributes (for example, if the food contains a lectin or is known to encourage bacteria overgrowth, etc) is recorded, then the next step is to see if a case can be built for the food having any specialized benefit (for example, sardines might become a superfood if increasing the amount of RNA nucleotides is desirable; artichokes because they encourage probiotic growth in a strain of bacteria known to be good for a certain blood type). Lacking either of these elements, the food is simply labeled 'food' and considered more or less neutral.
In the simple case of rice versus rice milk it is most likely additional gums in the milk that are the issue. Certain gums amplify the effects of problematic proteins in other foods.
People also ask a lot about peanut oil versus peanuts or cherries versus cherry juice. Usually it is a difference between one form that contains some sort of problematic protein versus the other that doesn't. Also, occasionally in the Genotype diet (unlike the BTD) with complex foods, sometimes one nutrient influences the value of another which alters the value of the food.
Here are blogs of mine tagged as 'genotype diet.' You will see some elements of the process discussed in detail in many of these entries.
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've spent the beginning of this New Year cleaning up the various sites that I administer. In finishing up work on the genomic wiki-like knowledge base that we built several years ago, I thought it might be helpful to suggest 25 of what I feel are the best articles on The Individualist.
These are not exactly 'consumer level' stuff; more likely it would be called 'pro-sumer level' and I recommend these articles for those die-hards who just have to know everything. If you are still trying to figure out what to do with spelt, tofu or agave syrup, you may want to wait a while before tackling them.
- ABH Antigens
- A-like Tumor Antigens
- ABO Blood Group
- ABO and Secretor Genetics
- Blood and Anthropology
- Biology of Carbohydrates
- Chromosome 9q34
- Disease and Blood Groups
- Founder Effect
- Genes and Environment
- Joseph Charles Aub
- Lamarckism Revisited
- Lectins Resist Digestion
- Lectins and the Intestines
- DNA Methylation
- Phenotypic Plasticity
- Secretor Status
- Stress Blood Groups
One of the great chin-scratchers of modern physical anthropology revolves around blood type, in particular why most indigenous populations of the New World have such incredibly high percentages of the gene for type O. Sometimes, especially as you move south of the modern US-Mexico border, the percentages almost reach 100%.
Since almost everyone agrees that human habitation of the New World began with migrations out of the Siberia, across the Bering Sea, and the population on the Russian Asiatic side shows no similar high percentage of type O; if anything the percentage frequency of the type O gene drops as we move further and further north and east. Several theories have been advanced to explain the apparent 'Bering Sea Bottleneck'.
The most often suggested is the genetic drift theory. The basic idea behind genetic drift is easy enough to understand. If you flip a coin two hundred times, there is a very good chance that your results will be somewhere close to 100 times coming up heads, and another 100 times coming up tails. Indeed, the more you flip a coin, the more likely (given that you have an honest coin) the results will be 50% head and 50% tails.
However, suppose that you instead only flipped the coin seven times; would it not be feasible on any given Sunday to flip five heads and two tails? Sure it is. That is how Las Vegas stays in business. Genetic drift is like that: A small population may have an uncharacteristic gene distribution simply because the genetic coin did not flip enough to have things even out.
So the Genetic Drift Theory of the 'Bering Bottleneck Type O Anomaly' posits that a small band of folks swam, walked or boated over the Bering Strait, and because their numbers were so small, the genes for A and B did not come along with the coin flip. This small number of colonist determined the future gene pool for the continent due to their exerting a 'founder effect'.
It's not a bad theory, except that in order to accomplish this, the numbers of Asian immigrants to the New World must be very small; along the order of a dozen or less, so that there is an even slight statistical chance that they could all be type O. However, even if the original colonizers of the New World numbered, say ten or eleven, the odds of those entire ten or eleven colonist being type O is about one in a thousand. Even if the number of colonists is dropped to five the odds only drop to one in thirty-two. (1) And that also assumes that there was one boatload or band of colonists, when common sense tells us that there must have been numerous attempts, though perhaps not all successful, to migrate to the New World.
The second theory is that of Natural Selection, which a lot of people equate with evolution, but it's not. Natural selection posits that perhaps a mixture of all blood types were part of the original migration, but for some reason, probably infectious disease, the type A and type B colonists died out. Of the two, Natural Selection is perhaps the stronger theory since there a definite likes between ABO type and susceptibility to small pox, syphilis, E. coli and tuberculosis, all of which probably killed lots of people back then.
However, as any honest exterminator will tell you, it's hard to kill them all.
A.E. Mourant addressed this issue in his book Blood Relations
"Like the absence of B in the Australian aborigines, the lack of B in the northern zone and of A and B in the southern zone raises a problem of world-wide importance. Was the B gene totally absent from the original populations from eastern Asia that ultimately reached Australia and America, or was the gene lost on the way? If so, was this due to genetic drift in relatively small isolated populations, or to natural selection? Early blood-group workers suggested that when man left Asia for Australia and America mutations for the A and B genes had not yet occurred. However, analogous if not identical genes occur in the higher apes at least, and so are several million years old. In the light of the discussion of O frequencies in Europe it is not difficult to see how, as a result of the elimination of A and B fetuses of O mothers, first the gene B (which is rarer than A) could have tended to disappear, and then A itself."(2)
Now, it has been know for a while (3) that human and primate ABO genes are somewhat analogous, let's just say that they are similar enough for our purposes, which is to say that the individual genes for A, B and (by default) O are 'old'. However, does it automatically lead us to assume that just because genes share a long history, does that mean we can assume that they will always exist in the percentage numbers? Of course not, we just say that with Genetic Drift: percentages change.
With apologies to Edward Tufte, let's take a look at the snazzy graphic I just did:
What you are looking at is the northeast corner of Asia and the northwest corner of North America at the Bering Strait, across and under-which one day your kids may be able to drive their cars. Not surprisingly, the colors of the map mean things: For example, the darker green the land is colored, the higher the frequency of the gene for type O; the lighter the color, the lower the percentage (less type O genes)
Now, first of all, note that these are indigenous populations, so the modern-day Alaskans and Siberians don't figure here that much here. What sticks out at you? Yup, there is lots of O gene the further east (the right side of ther map) you travel! But what else? Normally we might expect the trail of O genes to drift nicely along, but in our map the distribution is bi-modal: The incidence of O gene is higher at both ends of the map and lower in the middle. You can see that by looking at the bar graphs below, which not only looks at the relative 'percentage if each percentage' but also the percentage of land versus water: Each bar graph is actually a snapshot of one of the sixteen 'slices' of the map, the black lines.
So if anything, the more constricted that land mass became, the less you find the type O gene.
Interestingly, look at the red numbers on the map. They are the percentages of type B gene. Notice as well that the Asian side of the Strait has some of the highest percentage of Type B gene on the planet. What about on the American side?
Virtually no type B gene.
Now, to me this implies that there may well have been two waves, a 'First Wave' that contained very high percentages of type O gene and which had a relatively easy time getting across the Bering Strait (which may well have still been a land bridge) and who created the 'Founder Effect' in America, and a 'Second Wave' somewhat higher in Type A and much higher in Type B which followed but got stymied by the ecological changes and the closing of the land bridge.
So what I think is that both the Genetic Drift and the Natural Selection theories are correct, but I'm more inclined to move both of their occurrences with regard to blood type further back in time and much further west. In that case, rather than having crossed before the advent of the genes for A and B, our first American colonists would have walked across before the rest of Asia had a chance to recover from the results of its own initial 'flip of the coin.'
By which time there was no more walking there.
1. L. Luca Cavalli-Sforza. Genes People and Languages. University of California Press, 2000
2. Mourant, AE. Blood Relations, Blood Groups and Anthropology. Oxford University Press, Oxford, UK 1983.
3. Saitou N, Yamamoto F. Evolution of primate ABO blood group genes and their homologous genes. Mol Biol Evol. 1997 Apr;14(4):399-411.
More 'damned data' (Charles Fort's words, not mine): studies from the scientific literature which could pass for some of the more outlandish statements in The GenoType Diet:
The phenotype of an individual is the result of complex interactions between genotype, epigenome and current, past and ancestral environment, leading to lifelong remodelling of our epigenomes. Various replication-dependent and -independent epigenetic mechanisms are involved in developmental programming, lifelong stochastic and environmental deteriorations, circadian deteriorations, and transgenerational effects. Several types of sequences can be targets of a host of environmental factors and can be associated with specific epigenetic signatures and patterns of gene expression. Depending on the nature and intensity of the insult, the critical spatiotemporal windows and developmental or lifelong processes involved, these epigenetic alterations can lead to permanent changes in tissue and organ structure and function, or to reversible changes using appropriate epigenetic tools. Given several encouraging trials, prevention and therapy of age- and lifestyle-related diseases by individualised tailoring of optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.
Nutri-epigenomics: lifelong remodelling of our epigenomes by nutritional and metabolic factors and beyond. Clin Chem Lab Med. 2007;45(3):321-7
Epigenomics or epigenetics refers to the modification of DNA that can influence the phenotype through changing gene expression without altering the nucleotide sequence of the DNA. Two examples are methylation of DNA and acetylation of the histone DNA-binding proteins. Dietary components - both nutrients and nonnutrients - can influence these epigenetic events, altering genetic expression and potentially modifying disease risk. Some of these epigenetic changes appear to be heritable. Understanding the role that diet and nutrition play in modifying genetic expression is complex given the range of food choices, the diversity of nutrient intakes, the individual differences in genetic backgrounds and intestinal physiological environments where food is metabolized, as well as the impact on and acceptance of new technologies by consumers.
Epigenomics and nutrition. Forum Nutr. 2007;60:31-41.
Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, such as broccoli and broccoli sprouts. This anticarcinogen was first identified as a potent inducer of Phase 2 detoxification enzymes, but evidence is mounting that SFN also acts through epigenetic mechanisms. SFN has been shown to inhibit histone deacetylase (HDAC) activity in human colon and prostate cancer lines, with an increase in global and local histone acetylation status, such as on the promoter regions of P21 and bax genes. SFN also inhibited the growth of prostate cancer xenografts and spontaneous intestinal polyps in mouse models, with evidence for altered histone acetylation and HDAC activities in vivo. In human subjects, a single ingestion of 68 g broccoli sprouts inhibited HDAC activity in circulating peripheral blood mononuclear cells 3-6 h after consumption, with concomitant induction of histone H3 and H4 acetylation. These findings provide evidence that one mechanism of cancer chemoprevention by SFN is via epigenetic changes associated with inhibition of HDAC activity. Other dietary agents such as butyrate, biotin, lipoic acid, garlic organosulfur compounds, and metabolites of vitamin E have structural features compatible with HDAC inhibition. The ability of dietary compounds to de-repress epigenetically silenced genes in cancer cells, and to activate these genes in normal cells, has important implications for cancer prevention and therapy. In a broader context, there is growing interest in dietary HDAC inhibitors and their impact on epigenetic mechanisms affecting other chronic conditions, such as cardiovascular disease, neurodegeneration and aging.
Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007 Oct;17(5):363-9. Epub 2007 May 5
The purpose of this paper was to selectively review the literature on the role of epigenetics in mental illnesses. Aberrant epigenetic regulation has been clearly implicated in the aetiology of some human illnesses. In recent years a growing body of evidence has highlighted the possibility that epigenetics may also play a key role in the origins and expression of mental disorders. Epigenetic phenomena may help explain some of the complexity of mental illnesses and provide a basis for discovering novel pharmacological targets to treat these disorders.
Role of epigenetics in mental disorders. Aust N Z J Psychiatry. 2008 Feb;42(2):97-107.
A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.
DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19351-6. Epub 2007 Nov
Major efforts have been directed towards the identification of genetic mutations, their use as biomarkers, and the understanding of their consequences on human health and well-being. There is an emerging interest, however, in the possibility that environmentally-induced changes at levels other than the genetic information could have long-lasting consequences as well. This review summarises our current knowledge of how the environment, nutrition, and ageing affect the way mammalian genes are organised and transcribed, without changes in the underlying DNA sequence. Admittedly, the link between environment and epigenetics remains largely to be explored. However, recent studies indicate that environmental factors and diet can perturb the way genes are controlled by DNA methylation and covalent histone modifications. Unexpectedly, and not unlike genetic mutations, aberrant epigenetic alterations and their phenotypic effects can sometimes be passed on to the next generation.
Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 2006 Aug 30;600(1-2):46-57. Epub 2006 Jul 18