Dr. Catherine Shanahan On Dietary Epigenetics and Mutations

Dr. Catherine Shanahan is a board-certified family physician with an undergraduate degree in biology, along with training in biochemistry and genetics. She has also studied ethno-botany, culinary traditions, and ancestral health. Besides regularly appearing in and writing for national media, she has worked as director and nutrition consultant for the Los Angeles Lakers. On High Intensity Health, she was interviewed by nutritionist Mike Mutzel (Fat Adapted Athletes Perform Better). At the 31:55 mark in that video, she discussed diet (in particular, industrial vegetable oils or simply seed oils), epigenetic inheritance, de novo genetic mutations, and autism. This can be found in the show notes (#172) where it is stated that,

“In 1909 we consumed 1/3 of an ounce of soy oil per year. Now we consume about 22 pounds per year. In the amounts that we consume seed oils, it breaks down into some of the worst toxins ever discovered. They are also capable of damaging our DNA. Many diseases are due to mutations that children have that their parents did not have. This means that mothers and fathers with poor diets have eggs/sperm that have mutated DNA. Children with autism have 10 times the number of usual mutations in their genes. Getting off of seed oils is one of the most impactful things prospective parents can do. The sperm has more mutations than the egg.”

These seed oils didn’t exist in the human diet until the industrial era. Our bodies are designed to use and incorporate the PUFAs from natural sources, but the processing into oils through high pressure and chemicals denatures the structure of the oil and destroys the antioxidants. The oxidative stress that follows from adding them to the diet is precisely because these altered oils act as trojan horses in being treated by the body like natural fats. This is magnified by a general increase of PUFAs, specifically omega-6 fatty acids, with a simultaneous decrease of omega-3 fatty acids and saturated fats. It isn’t any difference in overall fat intake, as the 40% we get in the diet now is about the same as seen in the diet at the beginning of last century. What is different is these oxidized PUFAs combined with massive loads of sugar and starches like never seen before.

Dr. Shanahan sees these industrial plant oils as the single greatest harm, such that she doesn’t consider them to be a food but a toxin, originally discovered as an industrial byproduct. She is less worried about any given category of food or macronutrient, as long as you first and foremost remove this specific source of toxins.** She goes into greater detail in a talk from Ancestry Foundation (AHS16 – Cate Shanahan – Bad Diet, Bad DNA?). And her book, Deep Nutrition, is a great resource on this topic. I’ll leave that for you to further explore, if you so desire. Let me quickly and simply note an implication of this.

Genetic mutations demonstrates how serious of a situation this is. The harm we are causing ourselves might go beyond merely punishment for our personal sins but the sins of the father and mother genetically passing onto their children, grandchildren, and further on (one generation of starvation or smoking among grandparents leads to generations of smaller birth weight and underdevelopment among the grandchildren and maybe beyond, no matter if the intervening generation of parents was healthy).

It might not be limited to a temporary transgenerational harm as seen with epigenetics. This could be permanent harm to our entire civilization, fundamentally altering our collective gene pool. We could recover from epigenetics within a few generations, assuming we took the problem seriously and acted immediately (Dietary Health Across Generations), but with genetic mutations we may never be able to undo the damage. These mutations have been accumulating and will continue to accumulate, until we return to an ancestral diet of healthy foods as part of an overall healthy lifestyle and environment. Even mutations can be moderated by epigenetics, as the body is designed to deal with them.

This further undermines genetic determinism and biological essentialism. We aren’t mere victims doomed to a fate beyond our control. This dire situation is being created by all of us, individually and collectively. There is no better place to begin than with your own health, but we better also treat this as a societal crisis verging on catastrophe. It was public policies and an international food system that created the conditions that enacted and enforced this failed mass experiment of dietary dogma and capitalist realist profiteering. Maybe we could try something different, something  less psychopathically authoritarian, less psychotically disconnected from reality, less collectively suicidal. Heck, it’s worth a try.

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** I’d slightly disagree with her emphasis. She thinks what matters most is the changes over the past century. There is a good point made in this focus on late modernity. But I’d note that industrialization and modern agriculture began in the prior centuries.

It was in the colonial era that pasta was introduced to Italy, potatoes to Ireland, and sugar throughout the Western world. It wasn’t until the late 1700s and more clearly in the early 1800s that there were regular grain surpluses that made grains available for feeding/fattening both humans and cattle. In particular, it was around this time that agricultural methods improved for wheat crops, allowing it to be affordable to the general public for the first time in human existence and hence causing white bread to become common during the ensuing generations.

I don’t know about diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis. But I do know that the most major diseases of civilization (obesity, diabetes, cancer, and mental illness) were first noticed to be on the rise during the 1700s and 1800s or sometimes earlier, long before industrial oils or the industrial revolution that made these oils possible. The high-carb diet appeared gradually with colonial trade and spread across numerous societies, first hitting the wealthiest before eventually being made possible for the dirty masses. During this time, it was observed by doctors, scientists, missionaries and explorers that obesity, diabetes, cancer, mental illness and moral decline quickly followed on the heels of this modern diet.

Seed oils were simply the final Jenga block pulled out from the ever growing and ever more wobbly tower, in replacing healthy nutrient-dense animal fats (full of fat-soluble vitamins, choline, omega-3 fatty acids, etc) that were counterbalancing some of the worst effects of the high-carb diet. But seed oils, as with farm chemicals such as glyphosate, never would never have had as severe and dramatic of an impact if not for the previous centuries of worsening diet and health. It had been building up over a long time and it was doomed to topple right from the start. We are simply now at the tipping point that is bringing us to the culmination point, the inevitable conclusion of a sad trajectory.

Still, it’s never too late… or let us hope. Dr. Shanahan prefers to end on an optimistic note. And I’d rather not disagree with her about that. I’ll assume she is right or that she is at least in the general ballpark. Let us do as she suggests. We need more and better research, but somehow industrial seed oils have slipped past the notice of autism researchers.

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On Deep Nutrition and Genetic Expression
interview by Kristen Michaelis CNC

Dr. Cate: Genetic Wealth is the idea that if your parents or grandparents ate traditional and nutrient-rich foods, then you came into the world with genes that could express in an optimal way, and this makes you more likely to look like a supermodel and be an extraordinary athlete. Take Angelina Jolie or Michael Jordan, for instance. They’ve got loads of genetic wealth.

Genetic Momentum
 describes the fact that, once you have that extraordinary genetic wealth, you don’t have to eat so great to be healthier than the average person. It’s like being born into a kind of royalty. You always have that inheritance around and you don’t need to work at your health in the same way other people do.

These days, for most of us, it was our grandparents or great grandparents who were the last in our line to grow up on a farm or get a nutrient-rich diet. In my case, I have to go back 4 generations to the Irish and Russian farmers who immigrated to NYC where my grandparents on both sides could only eat cheap food; sometimes good things like chopped liver and beef tongue, but often preserves and crackers and other junk. So my grandparents were far healthier than my brother and sisters and I.

The Standard American Diet (SAD) has accelerated the processes of genetic wealth being spent down, genetic momentum petering out, and the current generation getting sick earlier than their parents and grandparents. This is a real, extreme tragedy on the order of end-of-the-world level losses of natural resources. Genetic wealth is a kind of natural resource. And loss of genetic wealth is a more urgent problem than peak oil or the bursting of the housing bubble. But of course nobody is talking about it directly, only indirectly, in terms of increased rates of chronic disease.

Take autism, for example. Why is autism so common? I don’t think vaccines are the reason for the vast vast majority of cases, since subtle signs of autism can be seen before vaccination in the majority. I think the reason has to do with loss of genetic wealth. We know that children with autism exhibit DNA mutations that their parents and grandparents did not have. Why? Because in the absence of necessary nutrients, DNA cannot even duplicate itself properly and permanent mutations develop.

(Here’s an article on one kind of genetic mutation (DNA deletions) associated with autism.)

Fortunately, most disease is not due to permanent letter mutations and therefore a good diet can rehabilitate a lot of genetic disease that is only a result of altered genetic expression. To put your high-school biology to work, it’s the idea of genotype versus phenotype. You might have the genes that make you prone to, for example, breast cancer (the BRCA1 mutation), but you might not get the disease if you eat right because the gene expression can revert back to normal.

Deep Nutrition: Why Your Genes Need Traditional Food
by Dr. Catherine Shanahan
pp. 55-57

Guided Evolution?

In 2007, a consortium of geneticists investigating autism boldly announced that the disease was not genetic in the typical sense of the word, meaning that you inherit a gene for autism from one or both of your parents. New gene sequencing technologies had revealed that many children with autism had new gene mutations, never before expressed in their family line.

An article published in the prestigious journal Proceedings of the National Academy of Sciences states, “The majority of autisms are a result of de novo mutations, occurring first in the parental germ line.” 42 The reasons behind this will be discussed in Chapter 9.

In 2012, a group investigating these new, spontaneous mutations discovered evidence that randomness was not the sole driving force behind them. Their study, published in the journal Cell, revealed an unexpected pattern of mutations occurring 100 times more often in specific “hotspots,” regions of the human genome where the DNA strand is tightly coiled around organizing proteins called histones that function much like spools in a sewing kit, which organize different colors and types of threads. 43

The consequences of these mutations seem specifically designed to toggle up or down specific character traits. Jonathan Sebat, lead author on the 2012 article, suggests that the hotspots are engineered to “mutate in ways that will influence human traits” by toggling up or down the development of specific behaviors. For example, when a certain gene located at a hotspot on chromosome 7 is duplicated, children develop autism, a developmental delay characterized by near total lack of interest in social interaction. When the same chromosome is deleted, children develop Williams Syndrome, a developmental delay characterized by an exuberant gregariousness, where children talk a lot, and talk with pretty much anyone. The phenomenon wherein specific traits are toggled up and down by variations in gene expression has recently been recognized as a result of the built-in architecture of DNA and dubbed “active adaptive evolution.” 44

As further evidence of an underlying logic driving the development of these new autism-related mutations, it appears that epigenetic factors activate the hotspot, particularly a kind of epigenetic tagging called methylation. 45 In the absence of adequate B vitamins, specific areas of the gene lose these methylation tags, exposing sections of DNA to the factors that generate new mutations. In other words, factors missing from a parent’s diet trigger the genome to respond in ways that will hopefully enable the offspring to cope with the new nutritional environment. It doesn’t always work out, of course, but that seems to be the intent.

You could almost see it as the attempt to adjust character traits in a way that will engineer different kinds of creative minds, so that hopefully one will give us a new capacity to adapt.

pp. 221-228

What Is Autism?

The very first diagnostic manual for psychiatric disorders published in 1954 described autism simply as “schizophrenic reaction, childhood type.” 391 The next manual, released in 1980, listed more specific criteria, including “pervasive lack of responsiveness to other people” and “if speech is present, peculiar speech patterns such as immediate and delayed echolalia, metaphorical language, pronominal reversal (using you when meaning me, for instance).” 392 Of course, the terse language of a diagnostic manual can never convey the real experience of living with a child on the spectrum, or living on the spectrum yourself.

When I graduated from medical school, autism was so rarely diagnosed that none of my psychiatry exams even covered it and I and my classmates were made aware of autism more from watching the movie Rain Man than from studying course material. The question of whether autism (now commonly referred to as ASD) is more common now than it was then or whether we are simply recognizing it more often is still controversial. Some literature suggests that it is a diagnostic issue, and that language disorders are being diagnosed less often as autism is being diagnosed more. However, according to new CDC statistics, it appears that autism rates have risen 30 percent between 2008 and 2012. Considering that diagnostic criteria had been stable by that point in time for over a decade, increased diagnosis is unlikely to be a major factor in this 30 percent figure. 393

Given these chilling statistics, it’s little wonder that so many research dollars have been dedicated to exploring possible connections between exposure to various environmental factors and development of the disorder. Investigators have received grants to look into a possible link between autism and vaccines, 394 smoking, 395 maternal drug use (prescription and illicit), 396 , 397 , 398 organophosphates, 399 and other pesticides, 400 BPA, 401 lead, 402 mercury, 403 cell phones, 404 IVF and infertility treatments, 405 induced labor, 406 high-powered electric wires, 407 flame retardants, 408 ultrasound, 409 —and just about any other environmental factor you can name. You might be wondering if they’ve also looked into diet. But of course: alcohol, 410 cow’s milk, 411 milk protein, 412 soy formula, 413 gluten, 414 and food colorings 415 have all been investigated. Guess what they’ve never dedicated a single study to investigating? Here’s a hint: it’s known to be pro-oxidative and pro-inflammatory and contains 4-HNE, 4-HHE, and MDA, along with a number of other equally potent mutagens. 416 Still haven’t guessed? Okay, one last hint: it’s so ubiquitous in our food supply that for many Americans it makes up as much as 60 percent of their daily caloric intake, 417 a consumption rate that has increased in parallel with rising rates of autism.

Of course, I’m talking about vegetable oil. In Chapter 2 , I discussed in some detail how and why gene transcription, maintenance, and expression are necessarily imperiled in the context of a pro-inflammatory, pro-oxidative environment, so I won’t go further into that here. But I do want to better acquaint you with the three PUFA-derived mutagens I just named because when they make it to the part of your cell that houses DNA, they can bind to DNA and create new, “de novo,” mutations. DNA mutations affecting a woman’s ovaries, a man’s sperm, or a fertilized embryo can have a devastating impact on subsequent generations.

First, let’s revisit 4-HNE (4-hydroxynonanol), which you may recall meeting in the above section on firebombing the highways. This is perhaps the most notorious of all the toxic fats derived from oxidation of omega-6 fatty acids, whose diversity of toxic effects requires that entire chemistry journals be devoted to 4-HNE alone. When the mutagenicity (ability to mutate DNA) of 4-HNE was first described in 1985, the cytotoxicity (ability to kill cells) had already been established for decades. The authors of a 2009 review article explain that the reason it had taken so long to recognize that HNE was such an effective carcinogen was largely due to the fact that “the cytotoxicity [cell-killing ability] of 4-HNE masked its genotoxicity [DNA-mutating effect].” 419 In other words, it kills cells so readily that they don’t have a chance to divide and mutate. How potently does 4-HNE damage human DNA? After interacting with DNA, 4-HNE forms a compound called an HNE-adduct, and that adduct prevents DNA from copying itself accurately. Every time 4-HNE binds to a guanosine (the G of the four-letter ACGT DNA alphabet), there is somewhere between a 0.5 and 5 percent chance that G will not be copied correctly, and that the enzyme trying to make a perfect copy of DNA will accidentally turn G into T. 420 Without 4-HNE, the chance of error is about a millionth of a percent. 421 In other words, 4-HNE increases the chances of a DNA mutation rate roughly a million times!

Second, 4-HHE (4-hydroxy-hexanal), which is very much like 4-HNE, his more notorious bigger brother derived from omega-6, but 4-HHE is derived instead from omega-3. If bad guys had sidekicks, 4-NHE’s would be 4-HHE. Because 4-HHE does many of the same things to DNA as 4-HNE, but has only been discovered recently. 422 You see, when omega-6 reacts with oxygen, it breaks apart into two major end products, whereas omega-3, being more explosive, flies apart into four different molecules. This means each one is present in smaller amounts, and that makes them a little more difficult to study. But it doesn’t make 4-HHE any less dangerous. 4-HHE specializes in burning through your glutathione peroxidase antioxidant defense system. 423 This selenium-based antioxidant enzyme is one of the three major enzymatic antioxidant defense systems, and it may be the most important player defending your DNA against oxidative stress. 424 , 425

Finally, there is malonaldehyde (MDA), proven to be a mutagen in 1984, but presumed to only come from consumption of cooked and cured meats. 426 Only in the past few decades have we had the technology to determine that MDA can be generated in our bodies as well. 427 And unlike the previous two chemicals, MDA is generated by oxidation of both omega-3 and omega-6. It may be the most common endogenously derived oxidation product. Dr. J. L. Marnett, who directs a cancer research lab at Vanderbuit University School of Medicine, Nashville, Tennessee, and who has published over 400 articles on the subject of DNA mutation, summarized his final article on MDA with the definitive statement that MDA “appears to be a major source of endogenous DNA damage [endogenous, here, meaning due to internal, metabolic factors rather than, say, radiation] in humans that may contribute significantly to cancer and other genetic diseases.” 428

There’s one more thing I need to add about vegetable-oil-derived toxic breakdown products, particularly given the long list of toxins now being investigated as potential causes of autism spectrum disorders. Not only do they directly mutate DNA, they also make DNA more susceptible to mutations induced by other environmental pollutants. 429 , 430 This means that if you start reading labels and taking vegetable oil out of your diet, your body will more readily deal with the thousands of contaminating toxins not listed on the labels which are nearly impossible to avoid.

Why all this focus on genes when we’re talking about autism? Nearly every day a new study comes out that further consolidates the consensus among scientists that autism is commonly a genetic disorder. The latest research is focusing on de novo mutations, meaning mutations neither parent had themselves but that arose spontaneously in their egg, sperm, or during fertilization. These mutations may affect single genes, or they may manifest as copy number variations, in which entire stretches of DNA containing multiple genes are deleted or duplicated. Geneticists have already identified a staggering number of genes that appear to be associated with autism. In one report summarizing results of examining 900 children, scientists identified 1,000 potential genes: “exome sequencing of over 900 individuals provided an estimate of nearly 1,000 contributing genes.” 431

All of these 1,000 genes are involved with proper development of the part of the brain most identified with the human intellect: our cortical gray matter. This is the stuff that enables us to master human skills: the spoken language, reading, writing, dancing, playing music, and, most important, the social interaction that drives the desire to do all of the above. One need only have a few of these 1,000 genes involved in building a brain get miscopied, or in some cases just one, in order for altered brain development to lead to one’s inclusion in the ASD spectrum.

So just a few troublemaker genes can obstruct the entire brain development program. But for things to go right, all the genes for brain development need to be fully functional.

Given that humans are thought to have only around 20,000 genes, and already 1,000 are known to be essential for building brain, that means geneticists have already labeled 5 percent of the totality of our genetic database as crucial to the development of a healthy brain—and we’ve just started looking. At what point does it become a foolish enterprise to continue to look for genes that, when mutated, are associated with autism? When we’ve identified 5,000? Or 10,000? The entire human genome? At what point do we stop focusing myopically only on those genes thought to play a role in autism?

I’ll tell you when: when you learn that the average autistic child’s genome carries de novo mutations not just in genes thought to be associated with autism, but across the board, throughout the entirety of the chromosomal landscape. Because once you’ve learned this, you can’t help but consider that autism might be better characterized as a symptom of a larger disease—a disease that results in an overall increase in de novo mutations.

Almost buried by the avalanche of journal articles on genes associated with autism is the finding that autistic children exhibit roughly ten times the number of de novo mutations compared to their typically developing siblings. 432 An international working group on autism pronounced this startling finding in a 2013 article entitled: “Global Increases in Both Common and Rare Copy Number Load Associated With Autism.” 433 ( Copy number load refers to mutations wherein large segments of genes are duplicated too often.) What the article says is that yes, children with autism have a larger number of de novo mutations, but the majority of their new mutations are not statistically associated with autism because other kids have them, too. The typically developing kids just don’t have nearly as many.

These new mutations are not only affecting genes associated with brain development. They are affecting all genes seemingly universally. What is more, there is a dose response relationship between the total number of de novo mutations and the severity of autism such that the more gene mutations a child has (the bigger the dose of mutation), the worse their autism (the larger the response). And it doesn’t matter where the mutations are located—even in genes that have no obvious connection to the brain. 434 This finding suggests that autism does not originate in the brain, as has been assumed. The real problem—at least for many children—may actually be coming from the genes. If this is so, then when we look at a child with autism, what we’re seeing is a child manifesting a global genetic breakdown. Among the many possible outcomes of this genetic breakdown, autism may simply be the most conspicuous, as the cognitive and social hallmarks of autism are easy to recognize.

As the authors of the 2013 article state, “Given the large genetic target of neurodevelopmental disorders, estimated in the hundreds or even thousands of genomic loci, it stands to reason that anything that increases genomic instability could contribute to the genesis of these disorders.” 435 Genomic instability —now they’re on to something. Because framing the problem this way helps us to ask the more fundamental question, What is behind the “genomic instability” that’s causing all these new gene mutations?

In the section titled “What Makes DNA Forget” in Chapter 2 , I touched upon the idea that an optimal nutritional environment is required to ensure the accurate transcription of genetic material and communication of epigenetic bookmarking, and how a pro-oxidative, pro-inflammatory diet can sabotage this delicate operation in ways that can lead to mutation and alter normal growth. There I focused on mistakes made in epigenetic programming, what you could call de novo epigenetic abnormalities. The same prerequisites that support proper epigenetic data communication, I submit, apply equally to the proper transcription of genetic data.

What’s the opposite of a supportive nutritional environment? A steady intake of pro-inflammatory, pro-oxidative vegetable oil that brings with it the known mutagenic compounds of the kind I’ve just described. Furthermore, if exposure to these vegetable oil-derived mutagens causes a breakdown in the systems for accurately duplicating genes, then you might expect to find other detrimental effects from this generalized defect of gene replication. Indeed we do. Researchers in Finland have found that children anywhere on the ASD spectrum have between 1.5 and 2.7 times the risk of being born with a serious birth defect, most commonly a life-threatening heart defect or neural tube (brain and spinal cord) defect that impairs the child’s ability to walk. 436 Another group, in Nova Scotia, identified a similarly increased rate of minor malformations, such as abnormally rotated ears, small feet, or closely spaced eyes. 437

What I’ve laid out here is the argument that the increasing prevalence of autism is best understood as a symptom of De Novo Gene Mutation Syndrome brought on by oxidative damage, and that vegetable oil is the number-one culprit in creating these new mutations. These claims emerge from a point-by-point deduction based on the best available chemical, genetic, and physiologic science. To test the validity of this hypothesis, we need more research.

Does De Novo Gene Mutation Syndrome Affect Just the Brain?

Nothing would redirect the trajectory of autism research in a more productive fashion than reframing autism as a symptom of the larger underlying disease, which we are provisionally calling de novo gene-mutation syndrome, or DiNGS. (Here’s a mnemonic: vegetable oil toxins “ding” your DNA, like hailstones pockmarking your car.)

If you accept my thesis that the expanding epidemic of autism is a symptom of an epidemic of new gene mutations, then you may wonder why the only identified syndrome of DiNGS is autism. Why don’t we see all manner of new diseases associated with gene mutations affecting organs other than the brain? We do. According to the most recent CDC report on birth defect incidence in the United States, twenty-nine of the thirty-eight organ malformations tracked have increased. 438

However, these are rare events, occurring far less frequently than autism. The reason for the difference derives from the fact that the brain of a developing baby can be damaged to a greater degree than other organs can, while still allowing the pregnancy to carry to term. Though the complex nature of the brain makes it the most vulnerable in terms of being affected by mutation, this aberration of development does not make the child more vulnerable in terms of survival in utero. The fact that autism affects the most evolutionarily novel portion of the brain means that as far as viability of an embryo is concerned, it’s almost irrelevant. If the kinds of severely damaging mutations leading to autism were to occur in organs such as the heart, lungs, or kidneys, fetal survival would be imperiled, leading to spontaneous miscarriage. Since these organs begin developing as early as four to six weeks of in-utero life, failure of a pregnancy this early might occur without any symptoms other than bleeding, which might be mistaken for a heavy or late period, and before a mother has even realized she’s conceived.

Inherited Learned Behavior

There is what we inherit from our parents and there is what we learn from our own experience. The two are distinct, right? Well, actually no they are not separate. This was further demonstrated by a Princeton study (Danger avoidance can be genetically encoded for four generations, biologists say):

“Moore and her colleagues investigated whether C. elegans can convey this learned avoidance behavior to their progeny. They found that when mother worms learned to avoid pathogenic P. aeruginosa, their progeny also knew to avoid the bacteria. The natural attraction of offspring to Pseudomonas was overridden even though they had never previously encountered the pathogen. Remarkably, this inherited aversive behavior lasted for four generations, but in the fifth generation the worms were once again attracted to Pseudomonas.”

This is not an entirely new understanding. Earlier research has found similar results in other species. The study that always fascinates me had to do with rodents. The scent of cherry blossoms was emitted in their cage and immediately following that the bottom of the cage was electrified. Unsurprisingly, the rodents jumped around trying to avoid the pain. The rodents learned to begin jumping merely at the presence of the scent, whether or not any electric shock followed. The interesting part is that their rodent descendants, even though never shocked, would also jump when they smelled cherry blossoms. And this lasted for multiple generations. A very specific learned behavior was passed on.

Of course, this isn’t limited to worms and rodents. Humans are harder to study, partly because of our longer lives. But researchers have been able to observe multiple living generations to discover patterns. I’m not sure if this exactly fits into learned behavior, except in how the body learns to respond to the environment. It’s similar enough. This other research found that the children and grandchildren of famine survivors had higher rates of obesity that had nothing to do wasn’t caused by genetics or diet. It is what is called epigenetics, how the genes get set for expression. The same genes can be switched on or off in numerous ways in relation to other genes.

I find that fascinating. It also makes for much complication. Almost no research ever controls for multigenerational confounding factors. Epigenetics has been largely a black box, until quite recently. To be certain that a particular behavior was directly related to specific genetics in a population, you would have to be able to follow that population for many generations. To fully control for confounders, that would require a study that lasted more than a century. It might turn out that much of what we call ‘culture’ might more correctly be explained as population-wide epigenetics.

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As a side note, this would have immense significance to dietary and nutritional research. Many of the dietary changes that have happened in modern society are well within the range of epigenetic involvement. And the epigenetic effects likely would be cumulative.

We have an ongoing and uncontrolled experiment going on. No one knows the long-term consequences of the modern industrial diet of refined carbohydrates, added sugars, highly processed vegetable oils, food additives, farm chemicals, microplastic, etc. It’s a mass experiment and the subjects never chose to participate.

Definitely, we have reasons to be concerned. Francis M. Pottenger Jr. studied the dietary impact on feline health. He fed some cats a raw food diet, others a cooked food diet, and a third group with a diet mixed of raw and cooked. The cats on the cooked food diet became sickly in the first generation and were entirely infertile after a number of generations.

This is not exactly similar to the human diet of industrial foods. But it points to how results play out across generations. The worst effects aren’t necessarily seen in the immediate generation(s). It’s future generations that have to deal with what those before them caused, as true for epigenetics as it is for national debt and environmental destruction.

Epigenetics, the Good and the Bad

Epignetics is what determines which genes express and how they express. Research on epigenetics for some reason has often focused on negative consequences.

In rodent research, scientists were able to induce a Pavlovian response to a smell that preceded a shock. The rodents would jump when the smell was present, even when no shock followed. And generations of rodents kept jumping, despite their never having been shocked at all. The Pavlovian response was inherited. In human research, scientists studied populations that had experienced famine. They looked at multiple generations where only the older generation had been alive during the famine. Yet all the generations following had higher rates of obesity. They inherited the biological preparation for famine.

One might start to think that epigenetics is a bad thing, almost like a disease. But that would be a mistake. Everything about who we are, good and bad, is shaped by epigenetics. To balance things out, I just came across some a more positive example. Health benefits get passed on as well. I would note, however, that this is what exacerbates inequality. This is why oppression and privilege get inherited not only through social conditions but in biology itself. This is all the more reason we should intervene to create the most optimal conditions for everyone, not merely the fortunate few.

This is why the political left emphasizes equality of results, beyond theoretical equality of opportunity. Opportunity is meaningless if it remains an abstract ideal disconnected from lived reality for most of the population. Telling people to get over the past is cruel and ignorant. The past is never past and, in fact, becomes imprinted upon the bodies of many generations, maybe across centuries. Historical injustices and transgenerational trauma are what our society are built upon, and much of it is within living memory, from the Indian Wars to Jim Crow.

It will require direct action to undo the damage and to promote the public good. That is the only path toward a free and fair society.

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Intergenerational transmission of the positive effects of physical exercise on brain and cognition
by Kerry R. McGreevy et al


Physical exercise is well known for its positive effects on general health (specifically, on brain function and health), and some mediating mechanisms are also known. A few reports have addressed intergenerational inheritance of some of these positive effects from exercised mothers or fathers to the progeny, but with scarce results in cognition. We report here the inheritance of moderate exercise-induced paternal traits in offspring’s cognition, neurogenesis, and enhanced mitochondrial activity. These changes were accompanied by specific gene expression changes, including gene sets regulated by microRNAs, as potential mediating mechanisms. We have also demonstrated a direct transmission of the exercise-induced effects through the fathers’ sperm, thus showing that paternal physical activity is a direct factor driving offspring’s brain physiology and cognitive behavior.


Physical exercise has positive effects on cognition, but very little is known about the inheritance of these effects to sedentary offspring and the mechanisms involved. Here, we use a patrilineal design in mice to test the transmission of effects from the same father (before or after training) and from different fathers to compare sedentary- and runner-father progenies. Behavioral, stereological, and whole-genome sequence analyses reveal that paternal cognition improvement is inherited by the offspring, along with increased adult neurogenesis, greater mitochondrial citrate synthase activity, and modulation of the adult hippocampal gene expression profile. These results demonstrate the inheritance of exercise-induced cognition enhancement through the germline, pointing to paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.