Written by Tucker Goodrich
Diseases of civilization
The world is facing a health crisis of unprecedented proportions. What have become known as chronic diseases, Western Diseases, or Diseases of Civilization (DC), have become pandemic as populations around the world adopt the lifestyle that first became prevalent in the country that perfected industrialization, the United States.
What are they?
The DCs revolve around the Metabolic Syndrome (MetSyn), a set of signs of disease that include central obesity, excess fats in the blood, high blood pressure and excess blood sugar. The diseases that associate with the MetSyn include the biggest killers in the industrial nations: heart disease, cancer, diabetes, neurological illnesses such as Alzheimer’s and host of seemingly unrelated autoimmune conditions.
Many causes have been blamed for the spread of the DCs; including lack of exercise, wheat consumption, excess consumption of calories, carbohydrates, sugar, animal fats, meat, environmental toxins such as pollutants or pesticides, genetics (most implausibly) and any cluster of associations dreadfully referred to as ‘multi-factorial’.
Each of these proposed causal factors fails, in my view, to explain the pandemic. What I’d like to introduce is an alternative hypothesis, one that better fits the observed epidemiology and that has clearly-described mechanisms that explain much of the pathology for the DCs.
Since it started in America, we’ll start with America. In the late 1800s and early 1900s three events occurred almost simultaneously. First, a method of detoxifying cottonseed oil, which had been an industrial waste product of the cotton industry, was discovered . Next came a method to ‘hydrogenate’ cottonseed oil, or make it into a solid-at-room-temperature edible fat . Thus cottonseed oil and the hydrogenated derivative known as Crisco—introduced in 1911—entered the food supply in large quantities for the first time [3, 4].
Simultaneously, America began to experience heart disease in large quantities. Previously a very rare condition, heart disease quickly became an epidemic, and the relatively new modern medical profession began to track it, and attempt to devise treatments . Similarly, cancer “control” became a concern, with the forerunner of the American Cancer Society being founded in 1913 .
The single biggest change in the American diet over the 20th century was the increase in seed oils, which increased 1000-fold 
America, a massive agricultural exporting nation, exported the fruits of the industrial revolution, which included new foodstuffs, including white wheat flour, sugar and vegetable fats— so called to distinguish them from the traditional animal fats that had been used as food since human evolution.
I will refer to vegetable fats as seed oils, to distinguish fats made from seeds such as cotton, corn, soy, rape and others from fats made from fruit like olives or palm fruit. This will become important later on.
Wherever American industrially-produced foods were introduced, DCs soon followed. Although not generally well known now, a number of doctors and scientists recognized the impact of industrial foods on populations abandoning their traditional diets for what has become known as the Standard American Diet (SAD) [8, 9, 10, 11]. I prefer the acronym MAD, Modern American Diet, as the American diet prior to industrialization was a largely meat-based one, and did not produce the same diseases, and will use that throughout [12, 13, 14].
Japan as the canary in the coal-mine
While there are many cases we could examine, perhaps the most telling was the MAD being introduced to post-WWII Japan. After the Japanese surrender, America took over the southern Japanese island of Okinawa, and used it for their base of operations. Unlike most other traditional cultures into which the MAD was introduced, Japan was a highly industrialized country. Yet Okinawans still ate a traditional diet that revolved around pork, yams, and fresh vegetables, and made them famous as one of the “Blue Zones”, a population with exceptionally long lifespans—in fact, the longest in the world .
What is less known is what happened after America took control. The first American fast-food restaurant opened in Okinawa, 9 years before Tokyo, to meet the American soldiers’ appetite. Okinawans also enjoyed American fast food and rapidly adopted it as their own [16, 17]. In that one generation, DCs exploded into Okinawa. Fathers attending the deaths of their sons became a common occurrence, with obesity, heart disease and cancer becoming common.
Hirome Okuyama, a Japanese scientist exploring the dramatic change in longevity in Okinawa, in 1996 published a paper pointing the finger clearly :
Dietary fatty acids – the N-6/N-3 balance and chronic elderly diseases. Excess linoleic acid and relative n-3 deficiency syndrome seen in Japan
“The age distribution of the survival rates of male Okinawans in 1990 is also interesting. The mortalities from all causes for the generations over 70 years of age were the lowest, whereas for those males less than 50 years old they were the highest among the 47 prefectures…”
In a single generation, Okinawa went from the lowest mortality in Japan to the highest
Seed-oils and refined flours brought DCs to Japan
This one incident clearly disproves a number of leading hypotheses on the emergence of DC. It’s clearly not genetic (although that’s a factor, especially in Japan), as gene networks underlying complex adaptations don’t change that quickly. It’s not just caused by total carbohydrates per se, as the Okinawans had a high carb diet with tubers, rice and fruit prior to Americans arriving .
Americans introduced much larger quantities of cheap refined flours which replaced the Okinawan carb sources. It’s not caused by meat, as the rest of Japan had a huge increase in meat consumption after WWII, and longevity increased, unlike in Okinawa. It’s not caused by animal fats, as they were rapidly replaced by cheap seed oils imported from America—which introduced a program to ‘Americanize’ the Japanese diet. It’s unlikely to be caused by saturated fats, as consumption of saturated fat was and remains lower in Japan than it was or is in America, and there are no mechanisms to explain how natural saturated fat causes disease. Environmental toxins are an unlikely explanation too, as, while Japan was industrialized, Okinawa didn’t experience a major change in that regard. There’s also no possibility of a local environmental factor in Okinawa, as Japanese who moved to America saw a similar increase in DCs. And just to throw it out there, this also disproves the cholesterol-heart disease hypothesis, as cholesterol is not associated with heart disease in Japan, but with increased longevity .
Excess Linoleic Acid Syndrome (ELAS)
In my reading, the diseases that surround the MetSyn share common traits. Inflammation and insulin resistance are oft-cited, but perhaps more significant traits include mitochondrial dysfunction, apoptosis (cell death), necrosis (tissue death) and genetic damage. These point to the common mechanism, named ELAS by Okuyama . I think it’s the best candidate for cause and best explanation of the MetSyn and related, chronic DCs.
What’s Linoleic acid?
Linoleic acid (LA) is an omega-6 (n-6 PUFA) fat which is considered essential to human and animal function. To head folks off at the pass, n-6 fats are found in all natural foods, plants and animals, so this isn’t something you need to avoid entirely – it’s not possible, nor necessary. There are three major fat types. LA is a polyunsaturated fat (PUFA) . It’s joined by monounsaturated fats (MUFA) such as oleic acid (named for olive oil) and saturated fats (SFA) such as stearic acid (named for steers, beef) or palmitic acid (named for palm oil). Fish oil is also a PUFA, but of the omega-3 variety (n-3 PUFA).
N-6 PUFAs are primarily made by plants, as are the similar n-3 PUFAs, and are concentrated up the food chain by animals eating those plants. The major sources of n-6 PUFAs in the MAD are oils refined from seeds and animals fed a high proportion of seeds. PUFAs have traits which make them of interest: they’re highly susceptible to oxidation (rancidity), unlike MUFA or SFA, and they’re used throughout the body as building blocks for tissues and for various signaling functions, after being converted into other chemicals.
The rancidity of PUFAs is the root of the problem
When food goes rancid, it usually smells and taste bad because the MUFAs and PUFAs have decomposed into peroxides . Both n-6 and n-3 PUFAs are highly likely to go rancid. Humans don’t detect the rancidity of n-6 PUFAs particularly well, they smell slightly stale and people actually prefer the taste. Contrast this to rancid n-3 PUFAs and imagine eating a rotten fish. No thanks! This is likely because concentrated n-6 foods were rare until the modern era .
The problems with rancid PUFAs
Both n-3 and n-6 PUFAs going rancid produce toxins, but the n-6 fats produce worse toxins. Most notable of these—and best studied—are acrolein, HNE, and MDA; although there are many others. Collectively, they’re called oxidized linoleic acid metabolites (OxLAMs). Acrolein is the acute toxin found in cigarette smoke. HNE is the best marker of effects of ELAS, as it is only produced from n-6 fats. All three are both produced in cooking or heating n-6 fats, but are also produced in the body. How toxic are these products? Cooking with seed oils is the leading cause of lung cancer in non-smoking women in China .
The list of toxicities of these three chemicals is most impressive. Acrolein is a biocide, meaning toxic to all life. HNE and MDA are less bad than that but are cytotoxic (kill living cells), mutagenic (induce mutations in DNA) and genotoxic (destroy DNA). OxLAMs are also highly reactive, which means they can combine with other molecules in the body, inducing and stimulating malfunction .
A primary mechanism of ELAS
An increase in n-6 consumption rapidly remodels the tissues in the body, as the fats are replaced throughout. In some tissues it happens within weeks, in others, like the human brain, it appears to take much longer . Increased n-6 consumption rapidly remodels cartilage, for instance, in all species studied, driving out the more stable omega-9 fatty acids (Oleic acid is a n-9 MUFA) . The same happens in mitochondria . As mentioned, mitochondrial dysfunction and DNA damage is a signature of the MetSyn and all related diseases. It’s seen in the fat cells in obesity, in the pancreas in diabetes and in the lining of the vessels of the heart in atherosclerosis, as well as in conditions of heart failure, fatty liver disease, neurological diseases such as Alzheimer’s and Parkinson’s, and, most notably, cancer.
OxLAMs trigger destructive chain reaction events
The mechanism for this is well-described, although not well-recognized. Excess n-6 linoleic acid (LA) consumption causes a remodeling of a molecule called cardiolipin in the mitochondria, the key energy-producing part of cells in all higher life forms. Cardiolipin comprised of LA is uniquely susceptible to oxidation compared to n-3 PUFAs, MUFAs or SFAs and this can happen spontaneously, as LA oxidation can be catalyzed by iron and cardiolipin is in constant contact with iron atoms in mitochondria. When cardiolipin oxidizes, a chain reaction can start. In vitro, so on the lab bench, this reaction continues until all cardiolipin is consumed, but luckily our body has countermeasures . In this process OxLAMs are produced. HNE, for instance, causes other cardiolipin molecules to oxidize, thus potentially causing a self-sustaining chain reaction. Reactive Oxygen Species (ROS) are produced in the reaction, which can also cause adjacent cardiolipin to oxidize . However, OxLAMs are several orders of magnitude more damaging to the bodies than simple ROS . HNE itself can induce the production of ROS. Oxidized cardiolipin causes mitochondrial dysfunction, as mitochondria are impaired with oxidized cardiolipin . What follows is mitochondria either collapsing, inducing apoptosis or necrosis . Apoptosis is seen throughout DCs—in cancer the cells are essentially ignoring the apoptotic signal and going rogue. The Warburg Effect noted in cancers is thought to be a cellular reaction to mitochondrial dysfunction in which the cells adopt an alternative energy pathway to better suit their uncontrolled proliferation. Thomas Seyfried, who has contributed much to the field of cancer metabolism, notes that dysfunctional cardiolipin has always been observed in cancer cells so far . Necrosis is seen in late-stage DCs, such as atherosclerosis, cirrhosis of the liver, heart failure and Alzheimer’s.
Once loose in the cells, the OxLAMs rapidly propagate, in a process known as Oxidative Stress (OxStr). HNE and MDA are the primary markers used to measure OxStr. ROS cannot leave mitochondria which are well prepared for them, but OxLAMs, being water-soluble, rapidly distribute throughout the cells and beyond. OxLAMs are also a regular part of mitochondrial function: HNE induces mitochondria to downregulate as a basic negative-feedback mechanism. Presumably this is to limit HNE creation and the spare the important antioxidant glutathione (GSH), as well as the aldehyde dehydrogenase enzyme (ALDH). GSH and ALDH are both important in protecting the body against evolutionarily-expected levels of HNE. Unfortunately for us, excess HNE can impair the function of both GSH and ALDH, thus allowing propagation of a runaway chain-reaction. Decreased levels of GSH are a typical sign of excess production of HNE, and a dietarily induced deficiency in GSH production predisposes to the DCs . A genetic deficiency in ALDH, which is highly prevalent in Japan and China, predisposes to all DCs [36, 37].
Tissue health as a function of levels of different fats
Confusingly, assays of n-6 status in pathological tissues often show a lower level of n-6 than other fats, and in these cases, addition of n-6 can actually improve function. This appears to be due to the chain reaction depleting LA or arachidonic acid (AA). The latter is a long-chain n-6 fat produced in the body from LA. N-6 levels are lower, but HNE levels have risen as N-6 is converted into OxLAMs [38, 39].
OxLAMs can bind to and alter the function of DNA, both in the mitochondrion and cell nucleus. In fact, they appear to be the leading cause of genetic damage, as the markers used for genetic damage are those generated by OxLAMs . Widespread generation of mutagenic and genotoxic chemicals in a live organism (in vivo) would go a long way towards explaining the genetic damage common in DCs.
OxLAMs are inflammatory
OxLAMs such as HNE directly induce inflammation, increasing inflammatory markers. Excess levels of LA-derived AA also induces inflammation, as it is used to build chemicals that send pro-inflammatory messages to the body. The mechanism of anti-inflammatory drugs such as aspirin, NSAIDs and Cox-2 inhibitors partially impairs this pathway.
It appears that a fundamental job of macrophages, an immune-system cell that attacks foreign cells, is to remove toxic OxLAMs from the tissues. Macrophage infiltration into tissue is seen in various DCs other than atherosclerosis, including obesity . One explanation is that the modifications made by OxLAMs to molecules cause those molecules to resemble Pathogen-Associated Molecular Patterns (PAMPs)—the molecules appear the same to macrophages as those on bacteria. Antibodies for oxidized LDL cholesterol (OxLDL) exist and development of these antibodies for therapy against atherosclerosis has revealed the antibodies to be equally sensitive to bacteria-derived lipopolysaccharides and OxLDL [42, 43]. Anti-cardiolipin antibodies are seen in several severe autoimmune diseases and are only sensitive to oxidized cardiolipin. Thus excess n-6 is a known cause of autoimmunity. It may be the fundamental cause of the increase in allergic diseases seen in Okinawa and around the world .
Specific disease pathologies
Cardiovascular Disease (CVD)
Goldstein and Brown received a Nobel Prize for discovering the LDL receptor . The next thing they tried to do was to induce the first stage of atherosclerosis, the conversion of macrophages into foam cells, which form the core of the atherosclerotic plaques that are thought to cause heart disease. They failed . Steinberg and Witztum then discovered that LDL must be modified through oxidation to cause macrophages to become foam cells [emphasis mine] 
The nature of the substrate for lipid peroxidation, mainly the [PUFAs] in lipid esters and cholesterol, is a dominant influence in determining susceptibility. As noted by Esterbauer et al. (52), there is a vast excess of [PUFAs] in LDL, in relationship to the content of natural, endogenous antioxidants. The importance of the fatty acid composition was impressively demonstrated by our recent studies of rabbits fed a diet high in linoleic acid (18:2) or in oleic acid (18:1) for a period of 10 wk. LDL isolated from the animals on oleic acid-rich diet were greatly enriched in oleate and low in linoleate. This LDL was remarkably resistant to oxidative modification, measured either by direct parameters of lipid peroxidation
Esterbauer discovered HNE which is always present in atherosclerotic lesions in all species. Oxidized n-6 PUFAs comprise a large proportion of the fats found in these plaques . OxLDL is the second-best known predictor of myocardial infarction, exceeded only by the OxLDL/HDL ratio (HDL is high-density lipoprotein) . Other aspects of circulatory disease, such as varicose veins and erectile dysfunction, also display increased rates of OxStr, as determined by the presence of OxLAMs. HNE and oxLDL are active throughout the pathological process to create foam cells, induce macrophage entrance into the lining of the vessels and spur apoptosis, necrosis as well as DNA damage seen in atherosclerosis.
Steinberg and Witztum followed up their rabbit study with a human study, which confirmed the importance of LA in creating OxLDL . Other studies have confirmed the effect. The most successful CVD prevention trial ever, the Lyon Diet Heart Study, which produced a 70% reduction in CVD rates, specifically reduced the consumption of LA and increased the consumption of n-3 and n-9 fats. It adds validation to the mechanism in humans but should be noted that the metabolites were not measured . Clearing HNE reduces atherosclerotic lesions in an animal model .
Similarly, oxidative activities of OxLAMs are seen in varicose veins, with these markers always being present at affected areas . Erectile dysfunction also appears to be a consequence of this process. Erectile dysfunction drugs, aside from the obvious effects, also have an antioxidant effect, and appear to prolong life in those with vascular diseases [54, 55].
Cancer is considered by many to not be a single disease but a wide array of diseases with, so far as we know, different causes. Viruses are a well-known cause of certain cancers, so it is safe to say that there is no single causal agent of cancer, however appealing that prospect would be. Much of the pathological behavior of cancer cells can be explained by the effects of OxStr: mitochondrial dysfunction, genetic damage, and a shift to glycolysis despite the presence of oxygen. HNE damages and impairs the function of pyruvate dehydrogenase, the enzyme that allows substrates produced by glycolysis to enter the mitochondria . This loss, combined with malfunctioning mitochondria emitting high rates of ROS and OxLAMs, may explain the metabolic dysregulation and anti-oxidant upregulation often seen in cancer cells.
Epidemiological work has shown low rates of cancer in populations eating traditional diets. In Asians, migration to industrialized countries increases breast cancer rates many-fold to the point where they reach Western levels . LA in the diet is in fact required to induce cancer in animals experimentally. The cancer-promoting effects of LA increase as it increases in the diet. This effect plateaus at around 4.4% of total energy, well below levels of consumptions seen in industrial civilizations .
One of the hallmark traits of cancer cells is the seemingly random mutations pervading unstable and disorganized nuclear genomes. There can be tens of thousands of mutations, much fewer than that  and sometimes none at all . For many cancers, the theory of it resulting from a single mutation doesn’t hold for most cancers. HNE and MDA both damage DNA in vivo and HNE preferentially damages the p53 gene. The latter is part of the body’s natural cancer-control mechanism and is defective in colorectal and hepatocellular cancers [62, 63].
N-6 PUFA consumption appears to be involved in obesity through several pathways. HNE, which is elevated in obesity, directly induces fat-storage across species at an intra-cellular molecular level by inducing pathological behavior in adipose tissue. The latter then fails to differentiate normally, leading to engorged adipose cells typical of obesity . As LA converts to AA, AA upregulation leads to increased production of endocannabinoids anandamide and 2-AG. Anandamide and 2-AG are the cannabinoids our body’s produce themselves and are so-called mimetics of trans-Δ⁹-tetrahydrocannabinol (THC) found in marijuana. Injection of endocannabinoids in animal models induces overeating, regardless of how full they feel . Elevated 2-AG is a typical feature in human obesity. Several studies by a group at the NIH have shown that dietary LA modulates production and levels of 2-AG and can directly induce obesity [66, 67]. Blocking the endocannabinoid receptor using a drug prevents obesity and metabolic syndrome, in animals and humans; however the side-effects like increased rates of suicide are unacceptable, leading to withdrawal of the drug .
One long-observed medical observation is that insulin resistance (IR) accompanies sepsis, a condition caused by infection. OxStr precedes IR in humans [69, 70] and OxLDL antibodies acutely reduce IR in a primate model of atherosclerosis . So the PAMPs found in OxLDL appear to be preoccupy by the immune system, with IR maybe being a reaction to a perceived infection. A reduced LA diet has been shown to reduce IR in two human studies; one measured OxLAMs, which were also reduced [72, 73].
HNE injected into skeletal muscle cells directly induces IR in those cells . Mitochondrial dysfunction is a common feature of diabetes and the resulting shift in energy production may play a role in IR. LA directly induces hyperinsulinemia in vivo in animal models of beta cells  (which produce insulin in the pancreas) and OxLDL directly causes beta-cell death. High levels of blood sugar (hyperglycemia) is a central feature of type 2 diabetes. Shulman et al.  argue an adipose-centric theory whereby hyperglycemia in type 2 diabetes results from uncontrolled adipose tissue lipolysis which feeds into liver metabolism as an excess of acetyl-CoA that will go on to spur further gluconeogenesis (the creation of new glucose). Others postulate a liver-centric theory where insulin directly changes the liver’s insulin-to-glucagon ratio, lowering it and thus leading to further gluconeogenesis . Regardless of the explanation one subscribes to about why type 2 diabetics have high blood sugars, high levels of HNE accompany dysregulation of gluconeogenesis. However, I’ve not seen a mechanism to explain it.
OxStr has become recognized as a major pathological factor in several severe neurological conditions, the incidence of which has been increasing along with increasing n-6 consumption, as seen with Alzheimer’s, Parkinson’s and Lou Gehrig’s disease (ALS). As opposed to rat brains, human brains appear to have a rate-limiter for uptake of LA. AA however, which is only produced in small quantities from LA but concentrates in tissues, does pass the blood-brain barrier. It’s been observed that AA increases prior to the onset of Alzheimer’s but decreases after its onset . AA is more subject to oxidation to HNE than LA is. HNE and other OxLAMs increase as AA decreases, perhaps indicating the self-perpetuating reaction is underway. HNE is always found in the pathological areas of the brain. Injecting HNE in an animal model induces the formation of beta-amyloid plaques , the signature of Alzheimer’s disease.
Non-Alcoholic Fatty Liver Disease (NAFLD) is a new disease which only appeared when n-6 consumption levels reached the current high levels. It mimics the effects of alcohol-induced Fatty Liver Disease (FLD). Like cancer, LA is required to induce FLD in animals. Very low levels of LA in the diet allows animals to consume up to 30% of energy as alcohol without pathology . Total Parenteral Nutrition (TNP) is a feeding strategy in humans with damaged or malformed guts. Fatty liver is a common consequence in TNP and replacing LA-rich oils with fish oils cures the condition in human infants . A small pilot study from Poland examining NAFLD in humans reduced the dietary levels of n-6 while providing the bulk of calories as carbohydrates. OxLAMs were reduced, as was insulin, HOMA-IR, weight and NAFLD resolved in 100% of subjects . HNE directly induces the fibrosis seen in advanced liver disease and in other DCs.
The leading cause of the blindness in the United States is Age-related Macular Degeneration (AMD). This is probably the only condition where the causal role of n-6 has not only been established but is becoming widely recognized. It’s illustrative of principles that should likely be informative for treating other DCs. The retina of the eye is rich in PUFAs and like other tissues is affected by diet. N-3 supplementation does not affect the progression of AMD unless it’s accompanied by low-n-6 intake . That combination is preventative—an evolutionarily-appropriate balance of the fats appears to be crucial. N-6 fats are very susceptible to oxidation by radiation, even visible light; blue light will induce retinal n-6 PUFAs to oxidize to highly toxic HNE. This may also be the causal pathway behind sunburn and skin cancer.
Osteoporosis, osteoarthritis, asthma, diabetic side-effects such as kidney failure, chronic pain and my personal favorite, sunburn, all have pathological roots in ELAS. Even high rates of violence have been compellingly linked to ELAS.
Several cofactors induce worsened OxStr is humans. In vitro, mixing LA, glucose and water at physiological concentrations induces peroxidation of LA into OxLAMs; the same has been shown in an in vivo animal model where increased n-6 feeding induced cardiolipin breakdown with subsequent induction of hyperglycemia causing mitochondrial collapse and cardiac necrosis [84, 85]. This is seen in heart failure, now epidemic amongst humans. Alcohol, fructose, smoking, radiation and infection all increased levels of OxStr and as in FLD, the effects of OxLAMs may play a role in the pathology associated with those factors. If two factors contribute to a disease but the disease only appears when one is present, it’s logical to conclude that the required factor is causal.
A final note on epidemiology
The epidemiology around n-6 consumption and DCs reminds me of an old joke. A policeman sees a drunk crawling around under a street light.
“What are you doing?”
“I’m looking for my keys!”
“You lost them here?”
“No, I lost them over there.”
“Why are you looking here, then?”
“Because this is where the light is!”
Applying epidemiology to nutrition is a very daunting task. Conducting it in a modern, industrial society is much easier than going to a traditional society with no government statistics or wealthy research institutions.
So most of the epidemiology looking at food consumption is done in the industrial nations, which have mostly had high incidences of seed oils for a very long time, before nutritional epidemiology became a science
Seed oils appear to cease increasing rates of cancer appearance after they comprise 4.4% of energy, and saturate tissues at 5% [86, 87]. Most industrial populations get more than 5% of energy from seed oils , so comparing one to another is to compare high to high, when what one wants to see is high vs low. Nevertheless, there are a number of studies looking at DCs in populations with differing food patterns, and they strongly support the hypothesis, with the incidence of DCs in populations consuming fewer seed oils being either fractional or non-existent . This likely explains the rapid increase in DCs seen in countries eating MAD-type diets.
According to several scientists I’ve read the work of or listened to lately, funding is missing. This is highlighted by Dr. Ron Krauss who works at the National Institutes of Health (NIH). According to him, the NIH have largely stopped funding clinical nutrition research. That, combined with the pro-n-6 PUFA bias in the American nutrition establishment, means that it’s unlikely much research will be done in the U.S. Much of the research seems to be done in either second-tier US institutions or in Europe and Asia. There’s a lot of lab work looking at mechanisms but not a lot of human interventional studies. The few that do exist however, like the Lyon Diet Heart Study, Christopher Ramsden’s work and the pilot LA metabolite intervention from Poland are all very compelling [90, 91, 92].
Research I would like to see on this question is an examination of PUFA status and OxLAM load in those few people still eating a traditional diet free from DCs, as well as interventional studies lowering n-6 PUFA.
Most such studies make no attempt to lower n-6, but just add n-3 on top of it. Due to competition between the two types of fat and as seen in AMD, this is unlikely to be a successful strategy
It’s essentially the modern Japanese diet: excess n-6 but good n-3. This has not prevented DC in Japan, but they do have lower rates of some diseases, like cardiovascular diseases.
HNE was discovered in the early 1980s, many decades after seed oils were introduced. The relationship between n-6 and endogenous production of signaling molecules was discovered later. N-3 fats became recognized as important after that. Research into this topic was in the 10s of papers in the 1970s and has increased by 135-fold today. It’s a burgeoning field but one that appears to be very much under the radar. In reading through the literature, I have come to the conclusion that the case for ELAS as the root cause of Diseases of Civilization is overwhelming.
Personally, I came to this topic through Stephan Guyenet and his excellent Whole Health Source blog. After months of reading his posts and reading the papers he linked to, I decided to cut seed oils from my diet on the spur of the moment, standing in front of the salad dressings in a cafeteria. My irritable bowel syndrome of 16 years disappeared in two days. My carb cravings disappeared as quickly, allowing me to discover an underlying wheat sensitivity. Sunburn became a thing of the past and as a pale blonde who had always assumed I was ill-adapted to life under the sun, this was revolutionary. My excess weight dropped off, along with my now too-large pants one morning, never to return. And after six broken bones in two years, I haven’t broken one since.
I started reading on the topic because I wanted to understand what had caused my personal health recovery – and I guess because I like puzzles.
What to do about excessive n-6 consumption?
Avoid eating seed oils, foods containing seed oils—junk food and animals fed high levels of grains and seed oils, like pork and chicken. Don’t go crazy with the nuts. Eat some fish. But no, you can’t fix ELAS with extra n-3 fats like fish oil, as the Japanese case demonstrates.
Except for fasting, this is the simplest health intervention ever, as it’s impossible to become deficient in n-6 fats when eating whole foods. Even if a fraction of the diseases with pathological signs pointing to n-6 are proven, you’ll still be far better off.
William E.M. “Bill” Lands spent his scientific career studying the role of n-6 and n-3 fats in the body. His conclusion, the title of an article written during his retirement, deserves to be the note to end on here [emphasis mine]:
Prevent the cause, not just the symptoms
Tucker is a technology executive in the financial industry who designs, runs and debugs complex systems. He started using the same approach for his own health after dealing with a couple of medical issues and realizing that the ‘solutions’ offered by medical professionals weren’t working or addressing root causes.