The Unsaturated Truth: Drop Seed Oils if You Want to be Healthy

The rise and risks of our most popular ‘vegetable’ oils, and what to choose instead. 

 

Down at H&G HQ, we’d rather make trends than follow them, so we’ve decided to take a deep dive into the slippery science of seed oils, aka vegetable oils, to see if our decision to keep well clear of them is science-backed and not just trendy. 

 

---

Executive Summary

• • A quarter of people in the UK have at least one diagnosed chronic illness.
• • Could dietary fats be playing a role?
• • Certain ‘essential’ fats must be included in our diets.
• • Linoleic acid (an omega-6 polyunsaturated fat) is an essential oil in tiny amounts.
• • With the advent of the oil industry circa 1911, our exposure to omega-6 polyunsaturated fats, including linoleic acid, multiplied exponentially.
• • 1912 heralded the first recorded heart attack—it quickly became the world’s leading cause of death and remains there today.
• • Seed oils (vegetable oils) make up 60% of the world’s most inefficient crops.
• • They provide almost no nutrients at all, but lots of calories.
• • Despite a ban, they do still contain small amounts of poisonous trans fats.
• • During processing and at home they begin to oxidise, creating reactive chemicals that cause oxidative stress and trigger inflammation.
• • Many restaurant cooking oils are highly toxic.
• • Most people today still believe omega-6 polyunsaturated fats are a ‘healthy choice’.
• • They overconsume them, pushing their levels of linoleic acid beyond normal.
• • This excess creates oxidative stress at a cellular level, triggering inflammation and errant immune responses.
• • Nutrients that defend against these pressures are used up quickly, leaving people open to diseases, including cardiovascular and metabolic diseases—two major ‘diseases of civilization’.
• • The ratio of anti-inflammatory omega-3 to omega-6 drops lower than ever before in our evolution.
• • This poor 3:6 ratio also causes inflammation.
• • Some landmark pieces of research that seemed to defend these oils as a ‘healthier’ choice over saturated fats, particularly from animals, turned out to be adulterated by the researchers.
• • The actual results showed a worsening effect of omega-6 polyunsaturated fats on cardiovascular disease and other disease markers.
• • The list of diseases associated with oxidised seed oils, and disproportionately high levels of omega-6 to 3 in the body is staggering.
• • Let the scientists battle it out, in the meantime, you have nothing to lose by reducing the worst offenders, including restaurant fried foods and ultra-processed junk foods.

---

Introduction

Chronic, non communicable diseases are increasing everywhere modernity comes to call. The industrial revolution changed food processing forever. Oils could be extracted from plants on an industrial scale. Advanced nations began consuming vegetable oils high in omega-6 polyunsaturated fats. Linoleic acid, which is an essential fat in tiny quantities, has now become a much larger part of our diet than it ever should have. Omega-6 oils are easily oxidised, especially when heated. The omega-6 oil has destabilised our omega-6 to omega-3 fat ratio. Cells are more likely to become damaged due to oxidation creating oxidative stress and chronic inflammation, two symptoms that characterise many chronic diseases including but not limited to: cardiovascular disease, cancer, dementia, and metabolic diseases including obesity and diabetes type 2.  You have nothing to lose by reducing your exposure to these oils.

 

---

 

Every year the world takes another step into a realm of technological brilliance. 

Time-consuming inconveniences are handed over to computer programmes, artificial intelligence and maybe tomorrow to robots.  Who knows what wonders the day after tomorrow will herald? But there is one thing we humans can’t hand over and that is the staggering array of chronic diseases from which so many of us suffer. 

And, the more technologically advanced we become, the more chronic disease seems to gather pace. 

Life expectancy is sliding backwards.  [1]

In the UK, 24.4% of us have at least one underlying chronic condition. No age group is exempted; 8.3% of our children, 66.2% of those over 70, and 19.6% of those in between suffer from some incessant disease.  [2]

That’s at least 15 million people. [3]

Chronically ill people account for half of all GP appointments, 64% of outpatient appointments and over 70% of inpatients. [4] But the NHS is a rickety bridge being stampeded. 

Those people existing in the poorest strata of our societies have a 60% higher prevalence of chronic disease, with a 30% increase in severity compared to those in the wealthiest. [5]

Our American cousins suffer worse. 

Since health surveyors in the US first recorded the state of chronic  disease in 1935 there has been a 700% increase—60% of Americans deal with at least one long-term condition. [6] Our modern era seems to be characterised by chronic inflammation [7], the root of so many persistent illnesses. 

Are you a player in a game over which you have no control? 

Or, is there something you can do to remove at least one thing that may be causing this epidemic of inflammation?  

We think there is, and you can start taking action by reading this article about industrialised seed oils and their transition from a mere drop within our diet, to a wave sweeping ancient fats aside. 

 

Fats 101

Eating as much protein and carbohydrate as you like wouldn’t prevent you from dying unless you added certain fats. 

Fats, scientifically called lipids, play an incredible array of different and critical roles within us. All fat-containing foods have varying fractions of the following three lipids. They are saturated fats (SFAs), monounsaturated fats (MUFAs), and polyunsaturated fats (PUFAs). PUFAs are further characterised as omega-3 and omega-6 fats. 

SFAs add rigidity and form to cell membranes (walls). 

Striking a perfect balance, MUFAs add a touch of fluidity allowing nutrients access and simultaneously permitting waste products and signalling molecules out. PUFAs add more fluidity and signalling properties—passing on electrical and chemical messages that are forever whizzing from place to place, from cell to cell. These characteristics allow PUFAs to perform certain tasks but make them more susceptible to damage by heat, light and oxygen—discussed later. 

The brain is a dense source of these fluid fats. With the water removed, the brain is 60% fat, half of which are PUFAs as the omega-3 DHA, and the omega-6 arachidonic acid (AA).  [8]  

Essential Fats

Certain fats are classified as ‘essential’. 

In a biological sense, essential means something that must be obtained from the diet because it cannot be synthesised inside the body. Humans can make SFA and MUFA from carbohydrates, so they are non-essential fats. Different types of SFAs and MUFAs are also found in abundance in our most ancient and nutritious foods—good old-fashioned animal products. So really it’s certain PUFAs that we must get from our diet. 

EPA (Eicosapentaenoic Acid), DHA (Docosahexaenoic Acid) and ALA (Alpha-Linolenic Acid) are essential omega-3 fatty acids that come under the PUFA umbrella. 

Linoleic acid is an essential omega-6 fatty acid that has been an important part of our evolution. Important but tiny. Linoleic acid and other PUFAs make up large fractions of modern plant oils typically made from seeds. These seed oils are ubiquitous which means we now eat more omega-6, particularly linoleic acid, than at any point in our evolution. 

This flip happened in just a handful of decades.

Familiarise yourself with the chart below and see what proportions of fat make up your favourites.

Which seed oils?

Firstly, we need to answer what are seed oils? These are industrially processed oils.

Seeds popular for their oil include cotton seeds, soybeans, corn, sunflower, safflower, canola (modified rapeseed), rice bran, peanut, and grape seed. These seed oils are high in PUFAs, specifically linoleic acid. We’re not talking about fruit oils such as olive, avocado, and coconut oil. The first two are high in monounsaturated fats, the last is high in saturated fat respectively. They have been eaten for centuries at least. We’re also not talking about linseed (flaxseed) oil, which is rich in an omega-3 called alpha-linolenic acid (ALA). 

Finally, conjugated linoleic acid (CLA) is a healthy omega-6 fat found in small amounts in ruminant animals and their milk.  [9]

Linoleic acid is central to any debate about seed oils. Look at the chart below to familiarise yourself with the levels of linoleic acid found in your favourite fats and oils. 

In the UK, sunflower is the most popular seed oil. 

In the US, it’s soybean oil.  

Why have these seed oils taken over our food supply? From where and when did they come? 

It all started in America with cottonseed oil. 

When Technologies Combined and Created Junk

‘Cottonseed was garbage in 1860, fertiliser in 1870, cattle feed in 1880, and "table food and many things else in 1890.”’ —The Rise of the American Cottonseed Oil Industry (1930) [10]

The world’s relationship with seed oils stretches back to the days of human-powered cotton plantations, recent independence from British dominion, and the catastrophic US North-South divide.

A mere two hundred years ago or so. 

Evolutionarily speaking, that makes them hot off the press. In 1799, the neonatal US government granted Charles Witting from Massachusetts a patent to extract oil from cottonseeds. His intention was to replace the sperm whale oil lamps lighting America with a cheaper convenient oil that involved fewer fatal harpooning accidents. 

As the decades flicked by, the idea and technologies exchanged hands a few times before a fistful of industrious men began building mills for the purpose of crushing, hulling and filtering cotton seeds to extract the oil at scale. In 1860, seven mills across the US were crushing about 50,000 tonnes of cottonseeds. By 1890, 119 mills were turning over nearly 20 million tonnes every year. 

Almost none of that was being eaten. 

What had previously been a waste product that unscrupulous companies were being fined for dumping into rivers, had now become an industry in its own right. Cottonseed oil was used for a million different purposes including as an industrial lubricant, in paints and coatings. For treating and softening textiles, in soaps and cosmetics, as lamp oil, and candle making to name a few.  

But it wasn’t until a few technologies united at the end of the 19th and beginning of the 20th Centuries that things began to change. 

Firstly, industrial bleaching and deodorising techniques turned spoiled, stinking oils into fresh-smelling, neutral-tasting products that people could consider eating. 

Secondly, Leon Meriot, a French engineer patented an extrusion machine. By applying heat and exerting substantial pressure, the innovative machine demonstrated the ability to extract considerably larger amounts of oil than the traditional method of crushing seeds between two large stones powered by trudging donkeys oblivious of their endless circular journey.   

Thirdly: The biggest leap forward was heralded by the soap and candle manufacturers, Proctor and Gamble (P&G). In 1908, the brothers-in-law purchased the rights to the hydrogenation process newly developed in Germany, and unwittingly sentenced millions of future people to an early death. [11]

Hydrogenation transforms oils into solid fats like lard. 

Annoyingly runny oils became conveniently spreadable with a longer shelf-life. They were also loaded with trans fats. By 1911, ‘all vegetable’ Crisco was born and P&G had their wonder product. Before the advent of any regulatory bodies, P&G were able to proclaim Crisco was a ‘healthier alternative to cooking with animal fats’. These claims were based on their wishes, not science.  

Just one year later, Dr John Herrick detailed the first recorded heart attack. His patient survived after ‘falling as flat as a pancake’ which surprised Herrick and his small group of contemporary cardiologists.[12]

Seemingly erupting out of nowhere, the next one hundred years saw heart attacks becoming increasingly common, eventually surpassing infectious disease to be crowned the world’s biggest killer. 

Cardiovascular disease remains in the top spot to this day with cancer hot on its heels.  

Amid growing concerns about the heavy usage of agricultural chemicals in cotton farming—and as the diet-heart hypothesis of saturated fat causing heart disease began to take hold of common sense—P&G swapped hydrogenated cottonseed oil for hydrogenated canola oil in the 1970s. Canola developed the same decade from rapeseed, was lower in the dreaded saturated fat than cottonseed (26% SFA). [13]

Deodorising, extrusion and hydrogenation made growing seeds for edible oil a big business. Vast areas of land usage swapped from nutrient-dense crops for consumption whole, to plants merely for their oil.

Exorbitant Land Usage

Oil crops are an environmental weapon of mass destruction. 

Today more oil crops are grown than fruits, vegetables, pulses, tree nuts and citrus fruits combined. [14] See table below: 

Making up three of the top five most inefficient crops, a single KG of seed oil from soybean, rapeseed (canola) or sunflower could produce between 30-50 KG of nutrient-dense vegetables. [15] Oil crops provide just 0.01% of our nutrients, but use between 20-30% of existing agricultural land. The clear winner four times over is the land required to grow soybeans. Next comes palm oil (which is not a seed oil) then rapeseed (canola), then sunflower.[16]

That’s three of the top four oils that didn’t exist in our diets in this refined form prior to about a century ago. [17]

These oils add very few nutrients, but provide lots of energy—precisely the opposite of what most people need. [18] But this poor ratio of nutrients to energy is not the only thing that these modern oils have added to our diets. As they go through industrial processing, they alter in ways that are far from harmless, from which the fallout is only just becoming clear.  

Damaged Goods

The industrial processing of the seed oils including soybean, sunflower and rapeseed (canola) looks like this:  

1. After gathering the seeds, they’re cleaned of debris.
2. Seed conditioning: The seeds are heated and or dried. 
3. Solvent Extraction: For seeds with lower oil content, such as soybeans or rapeseeds. The seeds are first ground into a fine meal and then mixed with a solvent (such as hexane) to dissolve the oil. The resulting mixture is separated, and the solvent is evaporated to obtain the crude oil. 
4. Refining: The extracted oil, known as crude oil, usually undergoes a refining process to remove impurities, and improve clarity, taste, and stability. 
1. Degumming: The crude oil is mixed with water and treated with acid to remove gums and other impurities. The mixture is then separated.
2. Neutralisation: In this step, the oil is treated with an alkali solution (usually sodium hydroxide) to remove free fatty acids and other acidic components.
3. Bleaching: The oil is passed through an adsorbent material (such as activated carbon or bleaching clay) to remove pigments, trace metals, and other impurities. This step improves the oil's colour and clarity.
4. Deodorization: The oil is heated in a vacuum to remove any remaining odours or unwanted flavours.
5. Final filtering: Any residual impurities are removed. 
6. Packaging and Storage: Proper storage conditions, including protection from air, light, moisture, heat, and bacterial breakdown. [19] 

PUFAs are prone to oxidation; a chemical process that makes the fats highly reactive and able to trigger oxidative stress and inflammation inside the body.  [20]

It’s this huge downside that is at the heart of our recommendations to avoid them in their refined modern guises. As mentioned in Fats 101, PUFAs (including seed oils) are damaged by oxygen, light and heat. They are exposed to these things to a greater or lesser degree whilst they’re processed.

The damage continues after processing while sitting quietly deceptive on supermarket shelves, or used for cooking (heat) at home or in restaurants (repeatedly heated). 

Once opened and every time afterwards, they’re exposed to the air (oxygen, moisture, bacterial breakdown).  This damage is in large part oxidation. 

Processing creates trans fats. 

After processing and before you heat them at home, seed oils can contain about 3.6% trans fats which are under the 0.5 grams per 14-gram serving size. This means the product can legally proclaim ‘0 grams of trans fats’.  [21]

So, despite a ban on industrially produced trans fats (natural trans fats are not the same) by 2023,  [22] they will continue to be in your seed oils before you’ve even opened the bottle. That alone is reason enough to leave them on the supermarket shelf. 

See the table below for approximate trans fat levels compared to the partially hydrogenated oils that have thankfully ceased since 2018. 

 

But, here’s some more bad news for you. 

Trans fats aren’t the only things you have to worry about in industrialised seed oils. Scientists generated aldehydes in soybean oil; America’s most popular choice. 

Aldehydes are a dangerous by-product of heating even under completely normal cooking times and temperatures like you would at home. [23] Aldehydes can be causal in both cancer [24] and heart disease [25] both of which we’ll discuss in more detail later.  

As mentioned, oxidation of seed oils—either in processing, storage, at home usage, or inside our bodies—causes a deterioration of quality making the fat reactive. [26] But the everyday usage that creates more oxidation than anything else is when seed oils are repeatedly heated. 

Hour after hour, day in and day out, restaurants all over the world boil and bubble their choice of seed oil in their deep-fat fryers. The more often they heat them, the more damaged and reactive they become. Whether or not these oils become oxidised and reactive is no longer debated. [27] 

UK and US governing bodies do not legislate how often a restaurant should re-use their oils, instead leaving it up to the restaurants to decide. Obviously, commercial eateries have a vested reason to use their oils right up until they become rancid. 

Researchers examined the quality of discarded oils and published their findings in the Food, Science and Nutrition Journal. [28] Here’s a quote: 

‘The majority of discarded oil from fast-food restaurants were over degraded containing hazardous secondary oxidative products.’

The scientists explicitly mentioned soybean oil for its high PUFA content, about 58%, [29] which is liable to oxidise and recommend not using it for frying. 

Meanwhile, the USDA recommends the following oils for deep frying: olive, peanut, canola, corn, grape seed, safflower, sunflower, and vegetable. Olive oil is the most expensive oil listed, so the chance of restaurants opting to glug this one into their fryers is minimal. On the same page, the Department of Agriculture suggests reusing cooking oil for about three months. [30] Three months!

In the UK, the Food Standards Agency gives chippies (chip shops) a few tips that amount to little more than ‘bang, shake and drain chips’. [31] It’s enough to make you never want to eat out again. 

Where are seed oils?

Seed oils of old

‘When fresh it can be used in cornbread for the same purpose and to as good an effect as lard, having nothing offensive in smell or taste, the latter resembling that of a hickory nut.’ Anon (1826). [32]

Prior to the industrialisation of oils–and apart from the odd farmhand dipping their cornbread into cold-pressed seed oils out of sheer curiosity or a lack of their preferred butter or lard or dripping–seed oils would only have featured in the human diet in tiny amounts inside, you guessed it, seeds.

Actually, the same PUFAs are found inside nuts and even inside animal products including egg yolks, the dark meat in poultry, salmon, pork and others in varying amounts. Poultry and pigs eat nuts and seeds more or less depending on their environment or feed. In many cases, these animals are fed soymeal. 

‘You are what you eat’ relates to the entire animal kingdom. 

The amount of PUFAs eaten by animals and humans alike is reflected within their own fats. [33] We need some, but we don’t want too much. There’s a sweet spot for everything, but this nuance is often overlooked in favour of the typically human belief that more of a good thing is always better. As you will learn, when it comes to PUFAs, this is categorically not the case.  

Modern consumption

Nowadays our love of seed oils is undiminished, if global consumption is anything to go by. 

In 2018, the global cooking oil market was valued at around USD 85.52 billion and is projected to rise to USD 130.30 billion in 2024. [34]  Data for UK consumption of these oils are harder to find, so we’ll use US data as a proxy. Since 1909, the use of soybean oil in the US has increased 1000 times, [35] making it the most popular seed oil in the country. [36] 

As you can see from the chart below, 

People have used seed oils for frying since about the early twentieth century—but it wasn’t until the late 1980s and early 1990s when the demonisation of saturated and animal fats (they’re not exactly the same thing) and cholesterol had reached their zeniths—that large-scale operations swapped over. 

After enormous pressure from the meddling Center for Science in the Public Interest (CSPI), McDonald’s swapped their beef tallow for a blend of ‘vegetable’ (mixed seed oils) in 1990. [37] 

The CSPI is a self-styled non-profit watchdog beset on the idea that the entire world should be vegetarian. They believe God ordained vegetarianism for Adam and Eve in the Garden of Eden, and if we hadn’t made a mess of that opportunity we would still be there eating nothing but plants. 

The institution is a huge proponent of any fat as long as it isn’t animal-based, and until 1993 when the science had well and truly come home to roost, that included trans fats.[38] Sadly, other fast-food giants followed McDonalds' lead and essentially swapped a stable and delicious fat for a highly reactive, steeped-in-trans fats concoction that spelt death for many.

People bought into the trend of modern scientifically approved ‘healthy’ fats with a  beautifully simple equation—high in PUFAs + low in SFAs = healthy.

Restaurant kitchens cancelled their decades-old contracts for beef dripping (tallow). 

They started pouring oils into their deep-fat fryers from enormous plastic containers–how convenient. Demand increased. 

The 1970s ‘go big or get out’ US agricultural policy pressured farmers into planting oil crops from ‘from fencerow to fencerow’. [39] Subsidised by the US government, it made better sense for farmers to grow oil crops than the nutrient-dense crops they had been growing for generations. Accordingly, they became cheaper at the checkout.

Best of all, according to scientists, these oils were healthier than the heart-stopping animal fats of old. 

What a boon, cheap and healthy! Who would have thought it? 

“When you really care about staying in shape, exercise alone isn’t enough. You’ve got to shape up the way you eat. That means using new Sunlite 100% sunflower oil as part of your diet to help you fight cholesterol..” Sunlight Sunflower Oil marketing from the 1980s. 

[Sunflower oil, the UK's favourite, is about 69% PUFAs. Notice the clear plastic bottle (light damage), and the fried chicken (heat damage).] 

Processing of foods became cheaper than ever, and manufacturers replaced butter–delectable but deplorable according to industry scientists and complete US government departments [40]– with cheaper oils that came with convenience. 

At home, people still cook with seed oils and drizzle them over salads believing they’re doing their hearts a favour. 

Food manufacturers use these industrialised oils in almost every processed food you care to read the label of, from organic baby snacks to salad dressing and everything in between. 

These modern foods are loaded with omega-6 PUFAs, especially linoleic acid. 

Is it conceivable that we’re having too much of this essential fat?  

The Major Player?

Linoleic Acid

Back when the twenties were swinging, George and Mildred Burr, husband and wife scientists, experimented on rodents by withdrawing certain fats from their feed.  [41]

They witnessed these luckless beasts failing to develop and grow during infancy. Also, their skin became blistered and sore. The Burr’s later said, ‘We were driven to the conclusion that the only thing that could be missing from the diet was linoleic acid. So, in March or April 1930, we wrote a paper announcing linoleic acid as an essential fatty acid, and that term was born.’  [42]

As with all scientific experiments these were not perfect, and there is some debate over whether linoleic acid is truly essential [43], because the omega-3 ALA may diminish the symptoms of linoleic deficiency.  [44]

However, you can leave these academic discussions to the scientists and not worry about whether or not linoleic acid is truly essential because it’s present in so many foods. The only recorded deficiency in humans was patients being fed intravenously [45] and those with fat-malabsorption diseases.  [46]

So the first question is, how much linoleic acid do we need to remain healthy? 

According to human research, between 0.5-2% of our daily energy requirements should come from linoleic acid to prevent deficiency. [47] That’s between 2.2-5.6 grams. These amounts can easily be obtained from whole foods: 

• Chicken thigh (200 grams) = 5 grams 
• Eggs (x5) = 4.5 grams 
• Sardines (100 grams) = 1.5 grams 
• Avocado (medium) = 2.7 grams 
• Walnuts (28 grams) = 10.8 grams 

The second question is, how much are we consuming?

In the UK, the National Diet and Nutrition Survey (2012) estimated adults consumed an average of 11 grams per day. [48] The US National Health and Nutrition Examination Survey estimates between 11-17 grams per day. [49]

It seems people all over the world are having between 13-22 grams (6-10% of their daily calories) from this omega-6 oil. [50] They get it from different food sources. Bulgarians and Brits, for example, get most of theirs from sunflower seed oil. 

The northern Europeans get their linoleic acid from mayonnaise and margarine. [51] Americans get the highest amounts from their favourite soybean oil. 

The third question is, are we eating too much? 

No upper limit has been set for linoleic acid because of a lack of intervention studies examining the consumption of large amounts—except that people are willingly consuming large amounts relative to about fifty years ago. So, how to know if this increase is detrimental to our health without directly using people as seed oil guinea pigs? 

A group of researchers conducted a review and meta-analysis (study of studies) to discover whether the increase in linoleic acid consumption could be measured inside human body fat. They discovered that over the past half a century, just as seed oil consumption ramped up, fat stores of this PUFA increased by 136%. [52]  

The authors found correlations between the increase in linoleic acid consumption and the staggering rise in obesity post-1980. Also, their correlations traced along with the rise in the inflammatory conditions of asthma and diabetes.[53]

Apart from correlations—which don’t show causations—is there any better evidence that we have crossed the safe threshold of linoleic acid consumption, and are now doing ourselves harm?

Diseases of Excess, the high omega-6:3 ratio

Oxidative Stress

In the UK, we get an average of 56.8% of our daily energy from ultra-processed food (aka junk). [54] 

For Americans, it’s 59.9%.[55] Junk foods are loaded with seed oils, which are high in linoleic acid and prone to oxidation at any stage of their production, their usage, and also when they’re in our cells. Manufacturers of seed oils add vitamin E, which is one of the fat-soluble vitamins (A, D, E, K). It works as an antioxidant to reduce the amount of oxidation in their oils. 

Oxidised oils stink, are reactive and dangerous, [56] and wouldn’t be best sellers. 

Vitamin E plays the same role in our cell membranes protecting those PUFA fats—like linoleic acid and omega-3s—from becoming oxidised and then damaging the cell. Vitamin E works by quenching free radicals, it does this by donating a hydrogen atom and making it stable and safe. A little like a roof with a rafter missing. Once replaced the roof is less likely to collapse and everyone beneath it can breathe a sigh of relief.

But by donating this atom to the free radical the vitamin E becomes reactive until it too is balanced by another of our body’s antioxidants—glutathione. 

Glutathione is considered our body’s master antioxidant. But it doesn’t last forever. It becomes depleted when faced with overwhelming oxidative stress partly due to poor dietary choices. A hallmark of many chronic diseases is glutathione depletion. [57] It plays a critical role in our health and longevity.[58]

But here’s the thing, and this simple fact is often overlooked. 

To have a robust antioxidant system, and to protect our cells from dysfunction and death by a chain reaction of oxidised lipids, we first must stop overloading our bodies with pre-oxidised fats (repeatedly heated) and fats liable to oxidise—excessive seed oils. 

At the same time, we must eat enough nutrients from our healthiest foods to build our most powerful antioxidants, including glutathione. 

When people include nutritious foods—the most nutrient-dense being offal, red meats, seafood, and leafy green vegetables—they hand their body the ammunition it needs to balance free radicals. 

They get to skip the chronic oxidative stress and inflammation. 

More than half of our energy comes from junk foods. Observational studies show a strong correlation between junk food diets and oxidative stress. This lifestyle choice is overwhelming our body’s antioxidant systems.[59]

The seed oils we’re frying with, adding to our salads, and eating with processed foods every few hours act like an unstoppable enemy hoard. Like routed soldiers, our antioxidant systems run out of ammunition. 

Inflammation is the result. When we do this day in and day out, chronic inflammation is the consequence. And, at the heart of almost any disease you care to mention chronic inflammation smoulders away.  [60]

Inflammation is at the heart of chronic illness 

Generally speaking, omega-3s are anti-inflammatory and omega-6s are inflammatory because of their role in the production of immune system molecules within the cell wall. [61]

It’s important to remember that inflammation is a critical, life-saving response by the body. We’re interested in reducing chronic inflammation–the inflammation that doesn’t switch off after it should. 

During our evolution, we ate a ratio of omega-6 to omega-3 between 1:4-6:1 depending on the availability of certain foods. 

Twenty years ago, that ratio was closer to 15:1-16:1. [62] That’s sixteen times more omega-6 PUFAs than omega-3 PUFAs.  Today it’s likely even worse given our growing obsession with omega-6 oils. When omega-6-rich foods dominate our diets, omega-3 foods tend to go wanting—people don’t tend to snack on oily fish. Also, there’s competition for the enzymes converting both linoleic acid and the omega-3 ALA. 

These enzymes take ALA and turn a small percentage of it into DHA and EPA.  [63]

When there’s a lot of linoleic acid around, those enzymes get busy changing it into arachidonic acid (AA). But the ALA conversion to our healthiest omega-3s is reduced. This is an excellent reason to eat oily fish and or supplement DHA and EPA. 

As mentioned, omega-3 has an anti-inflammatory role and omega-6 seed oils have an inflammatory action. This see-saw must be balanced again if we’re to stop the free radical formation and inflammation going up as antioxidants go down. [64]

Trials improving the ratio of omega-6:3 have shown benefits for an array of chronic diseases. We’ll look into some of the most serious now with a focus on linoleic acid.  

Does linoleic acid cause heart disease?

Researchers DiNicolantonio & O’Keefe (2018) give a summary of 29 scientifically backed reasons why linoleic acid is causative in heart disease. [66] We’ll cover some here. 

As you know, linoleic acid is easily oxidised at almost any step of its production and usage. As our consumption increases, our body's storage expands proportionally increasing the amount found inside fat cells and cholesterol. Most notably, linoleic acid increases in Low-Density Lipoprotein (LDL) cholesterol.

Because of its susceptibility, linoleic acid is the most likely fat inside LDL to become oxidised creating something called oxidised LDL (oxLDL).  [67]

OxLDL is a risk factor in heart disease because it combines with immune system molecules to create dangerous foam cells that combine to make atherosclerotic plaques–a hallmark of heart disease and the literal obstacle causing heart attacks and strokes.  [68]

Oxidised linoleic acid has been discovered in atherosclerotic plaques, and the more of it there is, the more serious the atherosclerosis. [69] Healthier arterial regions contain less oxidised linoleic acid.  [70]

DiNicolantonio and O’Keefe write in their review paper, ‘the amount of linoleic acid contained in LDL can be seen as the true ‘culprit’ that initiates the process of oxLDL formation as it is the linoleic acid that is highly susceptible to oxidation.’ 

They have expanded the current oxLDL theory of heart disease by taking a step further upstream towards the source of the problem, calling it the ‘oxidised linoleic acid theory of coronary heart disease’. 

When omega-3 PUFAs are consumed in place of linoleic acid an anti-inflammatory marker called CRP reduces and the risk of heart disease is mitigated to a certain extent.  [71]

Another marker of heart disease, a blood clotting agent called fibrinogen, increased in a group of people eating a high linoleic acid diet compared to those eating ALA, an omega-3 PUFA. 

Reducing blood levels of fibrinogen is associated with an 11% drop in heart disease risk.  [72]

Lowering total levels of cholesterol is still seen as the best way to mitigate heart disease risk. But the researchers turned things upside down when their results showed the linoleic acid group had decreased their total cholesterol levels but had suffered from more heart attacks and deaths—seven times more.

This is not the first time researchers have seen such seemingly contradictory results when trying to protect people from heart disease and death using linoleic acid.

A now infamous study called the Sydney Diet Heart Study took place between 1966 and1973.  [73]

The paper had been heralded as evidence against eating SFA and in support of swapping it with linoleic acid from oils and margarine. However, at the time large amounts of the data went mysteriously missing. 

In 2012, Dr Ramsden decided to seek the data out to see how it might change the results. After recovering the ‘lost’ data he added them to the results and discovered something abhorrent.  [74]

The group encouraged to swap animal fats for safflower oil (~76% linoleic acid) saw a predictable drop in cholesterol, yet there was a shocking 49% increase in overall mortality compared to the control group. Notably, cardiovascular and coronary heart disease fatalities rose by 56% and 61% respectively leading to catastrophic outcomes for the test group. 

Dr Ramsden, conversing with a veteran scientist on the original team, learned the data was omitted from the final report due to an inability to rationalise the results within the available time frame. 

In other words, the results were not what they were expecting so they buried them. Following this revelation, the esteemed British Medical Journal (BMJ) publicly requested full disclosure from researchers regarding unseen data, emphasising its global impact on evidence-based medicine.  [75]

A few years later Dr Ramsden decided to dig into another seminal anti-saturated fat paper. This time the Minnesota Coronary Experiment.  [76]

After reaching out to the late lead researcher's son, Dr Frantz Jr, Ramsden discovered a wealth of untapped data from the experiment hidden in disintegrating boxes under Frantz's family home.

The data, once converted into a modern format, revealed surprising results from a comprehensive and controlled study with 9,423 participants ranging in age from 20 to 97. These participants, who lived full-time in a nursing home and a state mental hospital, had their diets thoroughly controlled. 

This kind of trial is exceedingly rare. 

While a control group maintained a diet high in animal fats, an intervention group had half of these fats replaced with corn oil and margarine—high in linoleic acid.

The intervention group's cholesterol levels dropped by an average of 14 per cent. Success! No. 

Their mortality rate increased by 22 per cent for every 30-point drop in cholesterol. Results contrary to the prevailing diet-heart hypothesis. Furthermore, the intervention diet showed no protective effects against atherosclerosis or heart attacks. [77]

Here’s a quote from the DiNicolantonio and O’Keefe paper: 

‘In summary, numerous lines of evidence show that the omega-6 polyunsaturated fat linoleic acid promotes oxidative stress, oxidized LDL, chronic low-grade inflammation and atherosclerosis, and is likely a major dietary culprit for causing CHD, especially when consumed in the form of industrial seed oils commonly referred to as “vegetable oils”.’  [78]

Coronary heart disease (CHD) is still the world’s biggest killer. However, SFA consumption has decreased over the past three decades. On the other hand, omega-6 PUFA consumption has increased.  [79]

It seems like madness to continue blaming SFA despite this inverse relationship between its consumption and the continued rise of CHD. Surely the more likely player is the easily oxidised omega-6 PUFAs, the consumption of which has rocketed since shortly before the first recorded heart attack. 

Given that 80% of people with CHD are overweight and obese. [80] Perhaps seed oils play a role in the obesity pandemic beyond their caloric content.  [81]

Does linoleic acid make you fat?

We all know that the more calories you eat and the less you move the fatter you become, right? 

This belief has led us to another one of those blissfully simple equations, eat less + move more = fat loss. 

But what if there is more complexity to fat storage than just calories in, calories out? 

In the UK between the years 1998-2018, calorie consumption dropped slightly (3352 vs 3344). Over the same period in the US, it went up slightly (3658 vs 3782). 

See the chart below: 

Overweight and obese continue to climb in both countries, almost as if the calories we’re eating don’t tell the whole story.  

Between the years 1999-2016, Americans decreased their energy consumption from low-quality carbohydrates, mainly sugar, and increased their energy from ‘high-quality’ carbohydrates (whole foods), plant proteins and PUFAs.  [82]

SFA and total fats have also decreased over the past three decades across all Western countries.[83] Of particular interest to us is the increase in PUFAs. This is where animal studies are useful. They’re easily controlled versus human dietary studies that rarely take place in a controlled environment beyond a few weeks because they’re expensive to run and restrictive for the participants. 

Animals held inside a cage don’t nip to the corner shop, or chug a latte and biscotti later forgetting to mention it to researchers. 

Humans also do loads of unhealthy and healthy things that muddle the results (unhealthy and healthy user bias respectively) making it harder to pinpoint disease-causing lifestyle factors that aren’t monstrously obvious, like smoking. 

Researchers in Pakistan used a popular mixed cooking oil (equal parts olive, rapeseed [canola] and sunflower) and added it to rabbit feed. [84] They split the rabbits into three experimental groups plus a control group for comparison. The experimental groups all received identical food—the same calories, protein, carbohydrates and fats. 

There was one difference. 

The first group had the oil unheated. The second had it heated once. The third had it heated repeatedly. 

Versus the controls, the unheated group didn’t put on significant weight, the heated-once group added 6% body fat and the repeatedly-heated group put on a wardrobe-changing 45% body fat. The more frequently heated the oils were, the fatter the mice’s livers became and the more oxidative stress the little beasts exhibited in autopsy. Between 40-60% greater than the controls. 

As you know, the most oxidisable fat in this mix is the high linoleic acid sunflower oil.

Once that becomes reactive it begins damaging the more stable olive and rapeseed oils. All those oxidised fats have to be restabilised by our antioxidants as earlier explained. But, often they’re stored in our body fat where they continue to be reactive and inflammatory.  

As those rabbits found out the hard way, oxidised linoleic compounds are a marker of the ever-increasing non-alcoholic fatty liver disease (NAFLD). [85] Incidentally, between 2009-2018, this serious condition has expanded by 62% in children. [86]   

Human evidence that upsets the overly simplistic calories in, calories out model includes a study of 33,542 Europeans that reveals an interesting correlation between eating fried foods and obesity. [87] 

Researchers discovered the group eating the least amount of fried foods actually ate the most calories. Those eating the most fried foods ate fewer calories but were 26% more likely to be obese. Commercial eateries tend to use cheap seed oils and repeatedly heat them, as opposed to at-home frying where people use the fat once and are more likely to be using stable olive oil or animal fat. 

The more often a fat is heated the more oxidised it becomes and the more toxic products form. 

One of particular interest to us is, 4-Hydroxynonenal, known as HNE. 

HNE is a well researched highly toxic [88] by-product coming primarily from, you guessed it, oxidised linoleic acid. [89] It has been found in higher concentrations in people with cancer, heart disease, Alzheimer’s, inflammatory conditions, and just plain old obesity.  [90]

In fact, HNE may play a causal role in obesity. And, because cancer, CHD, Alzheimer’s and other chronic inflammatory conditions are more common in the obese, it’s becoming a molecule of interest for researchers across many fields.[91]

The first signpost pointing HNE towards fat accumulation was a 1992 rodent study.

Nishikawa and colleagues showed increasing HNE in corn oil became lethal to rats causing massive oxidative damage in the liver and kidney. But there was a side effect the researchers did not predict. They noted, ‘...low doses of HNE appeared to increase body weight gain”. [92]  

Going at the pace of science, in 2001, the Austrian PhD who discovered HNE, Hermann Esterbauer, found that by adding the reactive molecule to single-celled yeasts he could watch fat accumulate in as little as two hours. [93]

In 2008, a team of researchers genetically modified mice to have no ability to quench the free radical HNE with glutathione (the body’s primary defence against it). 

The higher the HNE levels, the more obese the mice became.  [94]

Remember that HNE primarily comes from dietary linoleic acid and that over the past half a century, linoleic acid has increased inside our body fat cells by 136%. In Americans, this increase mirrors the growth of obesity.  [95]

One of the highest sources of this pernicious little toxin is chips (fries), which are very likely cooked in repeatedly heated seed oils.  [96]

Unsurprisingly, Human data is just as disturbing as animal research. 

Mothers in the UK who ate more linoleic acid from PUFAs during their pregnancy had fatter kids aged four and six compared to mothers who had lower levels of the oil during their pregnancies. [97]

Researchers recruited 41 overweight women for a randomised, double-blinded, placebo-controlled clinical trial. 

Splitting them into groups, the first was given a high-fat breakfast made with 25 ml of soybean oil (~54% linoleic acid). The second group received the same dose but of extra virgin olive oil (~12% linoleic acid) [98]. After nine weeks, the olive oil group had lost 80% more fat than the soybean group. [99]  

Scientists split a group of 93 overweight Indian men with NAFLD into three groups for a six-month weight-loss intervention trial. [100] Each group consumed either olive oil, rapeseed (canola) oil, or soybean/safflower. The soybean/safflower group lost 770 grams (1.7lbs) of body fat,  the lower linoleic acid rapeseed (canola) lost 1.9 KG (4.2 lbs) and the olive oil group (lowest in linoleic acid) lost the most, 2.27 KG (5lbs). Both lower linoleic acid groups significantly improved their NAFLD, the soybean/safflower group did not.  

On the other side of the world, a team of scientists have spent years researching soybean oil. They specifically compared the effects of a high linoleic acid soybean oil to a low linoleic acid version and found that one of the world’s most popular oils causes some of the chronic diseases sweeping the globe, leaving death and dysfunction in their wakes—in mice anyway. 

The University of California, Riverside research team made the discovery, revealing that mice fed soybean oil exhibited obesity, diabetes, insulin resistance, and fatty liver.  [101]

All ‘diseases of civilization’. [102]

Building upon their previous research, the same group conducted another study in 2017. They found that by reducing the linoleic acid content in engineered soybean oil, the incidence of obesity and insulin resistance was significantly reduced. [103]

In 2020, the team went back to work with soybean oil, this time to see if the brain was affected by this ubiquitous lipid.  [104]

It was. 

But this time the prime mover was not linoleic acid. 

Specifically, the scientists found pronounced effects of the oil on the hypothalamus, a part of the brain where several critical processes occur.

In an interview with ScienceDaily, Margarita Curras-Collazo, an associate professor of neuroscience and lead author on the 2020 study, said ‘The hypothalamus regulates body weight via your metabolism, maintains body temperature, is critical for reproduction and physical growth as well as your response to stress.’

The team identified several mouse genes that demonstrated abnormal functionality after the rodents ate soybean oil. 

One of these genes is responsible for producing oxytocin, often referred to as the ‘love’ hormone. In mice fed soybean oil, the levels of oxytocin in the hypothalamus decreased. Oxytocin plays an underappreciated role in eating behaviours and energy regulation. [105]

Furthermore, the team discovered approximately 100 other genes that were influenced by the soybean oil diet. 

They suggest that these findings may have implications not only for obesity research but also for proper brain function and the development of diseases such as depression, autism, or Parkinson's disease.  [106]

These disturbances were seen with both the high linoleic soybean oil and the low linoleic version. The scientists admit they don’t know exactly what chemical exclusively in soybean oil seems to cause these genetic problems in the brain.  

Poonamjot Deol, one of the soybean oil research scientists said:

‘If there’s one message I want people to take away, it’s this: reduce consumption of soybean oil.’

Hunter and Gather Foods are listening, Poonamjot! 

Appetite control

‘Once you pop, you can’t stop’ was the enduring tagline by Pringles (1996). 

It’s proving to be truer than even their marketing department could have imagined. Pringles are made using a blend of vegetable oils. In Europe including the UK, they use sunflower, palm and corn oil. [107] In the US, it’s corn, cottonseed, soybean and/or sunflower. [108] Most of these oils are high in PUFAs including linoleic acid.

THC is a cannabinoid found in marijuana, it binds to cannabinoid receptors within people giving them ‘the munchies’ and making them binge eat. 

A drug called Rimonabant blocked this cannabinoid receptor resulting in weight loss. After being hailed as an obesity-tackling wonder drug, regulators withdrew it after it caused serious psychological harm including deaths by suicide. [109]

Linoleic oil derivatives—rich in junk foods, especially high-fat crisps like Pringles—trigger these same cannabinoid receptors which provoke addictive behaviours. [110] 

We seek out more food. Preferably the combination of carbohydrates, salt and fat. [111] You know, like Pringles. High-linoleic acid foods give us the munchies.

‘Once you pop, you can’t stop’ is bang on. 

Cognitive problems

As you know, people who eat lots of omega-6 PUFAs tend not to eat many omega-3 PUFAs. 

Also, high levels of linoleic acid inhibit the change of omega-3 from the plant-based form (ALA) to the most essential forms, EPA and DHA. 

Many people have a skewed ratio of 6:3 compared to those who avoid seed oils and junk foods and rather seek out omega-3 in oily fish and or supplements. 

Scientists know that omega-3s are crucial for brain function, not least because so much of the brain is made of DHA, a fat found in oily fish, but also because of their general anti-inflammatory roles.  [112]

What role do the omega-6 PUFAs play in cognition? 

Like DHA, a similar amount of the omega-6 PUFA, arachidonic acid (AA), is also found in the brain. [113] We also know that linoleic acid is an essential fat, but, as you have seen, eating an excess of it, especially relative to omega-3, causes a host of oxidative stress and inflammatory symptoms.

A review of 14 studies in humans shows a link between a high dietary omega-6 to omega-3 ratio and cognitive decline and the incidence of dementia. [114] 

A Chinese study demonstrated an association between age-associated cognitive decline and high levels of omega-6 in the blood, although they don’t mention the type of PUFA they were measuring. [115]

In a seven-year study of young people, an imbalance of this important 6:3 ratio increased their risk for mood disorders. The researchers found a high omega-6 to EPA and DHA (omega-3s) ratio was positively correlated with an increase in mood disorders.  [116]

As mentioned vitamin E is added to these oils to help protect them from oxidation, but the fat-soluble vitamin can only protect so much. 

During five trials in the 1950s and 1970s, researchers fed chicks a high linoleic, low vitamin E diet. [117] Unprotected, the omega-6 oxidised causing severe trauma in the chick brains. Inflammation, bleeding, loss of motor control and finally death. This damage was not seen when swapping linoleic acid for alpha-linolenic acid (ALA). [118]

More chicken and rodent studies followed, showing oxidised linoleic acid causing brain inflammation and associated dysfunctions. [119]

In humans it has been convincingly shown that the more linoleic acid a mother eats, the more is present in the breast milk. [120] Between 1970 and 2000, the amount of linoleic acid in breastmilk rose from 7% of all the fatty acids in the milk to 12%.  [121]

In terms of the energy it provides, this 12% linoleic acid content equals 8% of the total energy, which is between 4 and 8 times higher than the minimum 1-2% of energy from linoleic acid that growing babies need. [122]

A study found that if a mother's breast milk had a high amount of linoleic acid—more than 9.7% of all fatty acids—it was linked to lower movement and thinking skills in children aged 2-3 years. [123] 

Researchers used the same cohort and found this high-linoleic acid content was connected to lower verbal intelligence scores when the kids reached 5-6 years old. [124]

In fact, kids who were fed this high-linoleic breast milk had thinking skills similar to children who weren't breastfed at all. These effects seemed to happen regardless of the amounts of other fatty acids (AA or DHA) in the breast milk, indicating that too much linoleic acid in breast milk (which reflects the mother's diet) could directly affect brain development.

Other research supports these findings. One study found a negative relationship between the amount of linoleic acid in breast milk and the thinking skills of 15-year-olds, indicating that a mother's omega-6 PUFA intake could have a long-term impact on her child's cognitive abilities.  [125]

Another study reported that higher levels of linoleic acid in a mother's blood during the middle of her pregnancy were associated with a greater risk of autism traits in her child by the age of 6. [126] 

A 2017 study found that if pregnant women consumed a diet high in linoleic acid compared to the omega-3, ALA, it doubled the risk of their babies showing delayed mental and movement development at 6 months old. [127]

Ameer Taha, a scientist reviewing the correlations and causations of linoleic acid on the brain, says in the conclusion of his paper Linoleic Acid—good or bad for the brain?:

‘Pre-clinical and clinical studies dispel previous assumptions that [linoleic acid] is a benign fatty acid in the brain. On the contrary, when present in excess and chronically, it induces ataxia [coordination and balance] in chickens, promotes neuroinflammation in rats and is linked to abnormal neurodevelopment in humans.’ [128]

Ramsden et al. (2015) reported that dietary linoleic acid lowering from 7% to 2% of daily energy combined with a high EPA and DHA diet (~1.5 g per day) for 12 weeks, reduced migraine frequency and improved quality of life in patients with drug-resistant migraines. [129]

In the words of Columbo, ‘Oh, just one more thing’. 

Oxidised linoleic acid products, including HNE, are found in the brains of people suffering from Alzheimer’s disease and related dementias.  [130]

Can seed oils cause cancer?

In research conducted by the Los Angeles Veterans Administration (1969), scientists split a cohort of men into two groups, altering the fats in each. 

One group had 10% of their total fats as linoleic acid, the other had 38%. [131] The researchers were surprised to see the higher linoleic acid group exhibit an 82% greater chance of succumbing to cancer compared to the control group, who hadn’t augmented their consumption of fat from high linoleic seed oils.  [132]

Despite randomization, the low linoleic group was composed of twice as many heavy smokers. Yet, they still recorded a substantially lower incidence of cancer-related deaths.

The average linoleic acid concentration of the volunteer's fat tissue was initially 10.9%. During the last part of the trial, which lasted eight years for some, linoleic acid concentration in their fat tissue approached 33.7%. 

Skip forward thirty years and observational studies from Japan have linked breast cancer and colon cancer to a high intake of linoleic acid, especially when combined with low levels of dietary omega-3s.  [133]

These studies don’t show causation which is why they’re easy to ignore, especially because seed oils are so cheap and convenient! The next logical step is to look at animal research. 

Researchers injected live human breast cancer cells into mice. [134] Splitting the little critters into two groups, they fed the first group 2% of their total fat energy from linoleic acid, and the second group 12%. 

Both types of tumours started growing rapidly, especially in the high-linoleic acid diet group. 

At the end of the study, the high-linoleic diet group’s cancer was significantly heavier than in the low-linoleic diet group. The mice on the high-linoleic acid diet also had more lung metastases compared to the low-linoleic acid diet group.

Once again, we’ve come to evidence that it’s the oxidation of these fats that are the instigators of disease. 

In 2021, a mouse study showed a high linoleic acid diet (safflower oil) versus a high oleic acid (olive oil) promoted breast tumours by damaging cancer-fighting immune cells after becoming oxidised. [135] The oils were not heated or deliberately oxidised by the scientists. The oxidised linoleic acid caused mitochondrial dysfunction changing the way they produce energy, a major hallmark of cancer. [136] In turn, this alters genetic expression within the cell which is considered a marker of cancer and many other chronic diseases. [137]  

Mitochondrial dysfunction

Mitochondria are tiny structures found within almost all cells of the body. Often referred to as the ‘powerhouses’ or ‘engines’ of the cell because they generate most of the cell's supply of adenosine triphosphate (ATP), our body’s unit of energy. 

They are unique among cell organelles as they have DNA separate from the cell's main genetic material and are thought to have evolved from free-living bacteria that entered into a symbiotic relationship with our cells aeons ago.  [138]

The role of mitochondria also extends to other cellular processes such as cell signalling, cellular differentiation, cell growth, and even cell death. 

An excessive amount of linoleic acid in the diet can destabilise the mitochondria’s inner membrane, making it more likely to be damaged. [139] As mitochondria become damaged, they pump out more than usual reactive oxygen species (ROS) as a by-product of their ATP synthesis. Like an old engine sputtering out gritty, tar-black smoke from a rusty exhaust pipe choking everyone around it.  

The more omega-6 PUFAs you have in the mitochondria, the more likely they are to oxidise potentially creating a cascade of oxidative stress and inflammation in whichever organ cell they happen to be located. 

Take the liver, for example. You’ve already read that oxidised linoleic acid can cause non-alcoholic fatty liver disease (NAFLD) and that by reducing high linoleic oils like soybean and safflower in the diet the condition begins to improve. 

A dire progression of NAFLD is nonalcoholic steatohepatitis (NASH), characterised by advanced fat accumulation, inflammation and liver cell damage, which can lead to scarring (fibrosis), cirrhosis, and liver cancer. 

A mouse study (2018) showed oxidative products from linoleic acid caused serious mitochondrial damage in liver cells, leading to inflammation, cell death and NASH. [140] Another study showed that reducing omega-6 PUFAs protected rodents from NASH. [141] 

These dangerous molecules diminish in humans when omega-6 PUFAs are reduced.[142]

Monkeys fed a mixed ‘vegetable oil’ showed similar mitochondrial damage resulting in liver inflammation and cell destruction by oxidised fats. [143]

Oxidised fats and diabetes

In a comprehensive review of scientific literature, researchers scrutinised the possible associations between the levels of linoleic acid in adipose tissue and diabetes. 

Their findings highlighted a corresponding increase between the rising content of linoleic acid in American body tissue and the escalating prevalence of diabetes and obesity. [144] This doesn’t prove causation but given the other evidence, it might be prudent to take note. 

Diabetics have higher amounts of oxidised fats within their high-density lipoprotein (HDL) versus healthy controls. 

This correlates strongly with the amount of oxidative stress in the cells with which HDL interacts. [145] HDL-cholesterol is supposed to act as an antioxidant and as such has vital anti-inflammatory roles. [146] Hence its name ‘good cholesterol’.  

Lowering dietary linoleic acid reduces the amount of oxidised linoleic metabolites that seem central to the growing problem of diabetes. [147] Also, a reduced omega-6 to omega-3 ratio has an anti-inflammatory effect protecting the insulin-secreting cells in the pancreas.  [148]

Evidence for eating seed oils

Despite all this evidence, the world in general still seems to think they’re doing themselves, and their hearts a favour by chugging these oils in place of other less processed, more ancient fats. So, what evidence is there that allows people to be so content to do so? 

When Dr Ramsden recovered the lost data from the Sydney Diet Heart trial and Minnesota Coronary Experiment, the conclusions of both were turned upside down. 

The diet-heart hypothesis, so popular at the time and still lingering, seemed no longer to make sense—which is why the data had been hidden in the first place. The prevailing wisdom was that a diet rich in SFA would raise cholesterol and therefore your risk of cardiovascular disease and death. 

What they found was that the intervention group eating omega-6 PUFAs high in linoleic did indeed lower their cholesterol levels, but had more cardiovascular disease and deaths. 

This must mean that PUFAs are actually the problem, not saturated fats. But there is another possibility. 

The PUFAs given to the intervention group were in large part margarines which in the 1960s and 1970s were loaded with trans fats. Without a doubt, trans fats cause cardiovascular disease and death. Perhaps this is what killed more of the intervention group.  [149]

In a (2018) meta-analysis of randomised control trials (RCTs)—considered the gold standard of research, provided a balanced selection of papers is considered—the prestigious Cochrane Review concluded:  [150]

There is limited, low-quality evidence to suggest that increasing omega-6 fats does not significantly affect all-cause mortality or cardiovascular disease events. It's unclear whether consuming PUFAs impacts cardiovascular mortality, coronary heart disease events, major cardiac and cerebrovascular events, or stroke, as the evidence quality is very low. No notable dose-response or duration effects were found.

They continued by saying that omega-6 fat intake might slightly reduce the risk of myocardial infarction, with low-quality evidence supporting this claim.

High-quality evidence suggests that increasing omega-6 fats mildly reduces total serum cholesterol in the long term. It probably has minimal to no impact on body mass, blood fats, HDL, or low-density lipoprotein.

Population-based research on omega-6 seed oils shows associations between swapping 5% SFA for linoleic acid with improved health.  [151]

In a review of 30 observational studies, a team of scientists found a strong correlation between higher levels of linoleic and lower risks of total CVD, cardiovascular death, and strokes.  [152]

A high linoleic intake (5% and 10% of total daily energy) showed a slightly lower total mortality risk compared to the lowest intake. 

For cancer mortality, the more linoleic acid in the diet the lower the risk. 

When excluding initial cancer patients, these risks are reduced further. Also, the risk of heart attack deaths consistently decreased with each 5% increase in linoleic intake. [153]

A study of 20 prospective observational studies found linoleic acid may have long-term benefits for the prevention of type 2 diabetes.  [154]

Let’s wrap this up

The Cochrane review of randomised control trials  [155] is, by their admittance, not good evidence of anything except the fact that increasing PUFAs in one’s diet reduces cholesterol. 

Given that there is much more to the CHD story than just cholesterol levels, that doesn’t tell us much. 

In summary, they admit the research was ‘limited’, ‘low-quality’, ‘very low-quality’, making ‘little or no difference to CHD’ and even that ‘there was a suggestion of greater protection in participants with lower baseline omega‐6 intake across outcomes’. 

Simply put, the randomised control trials didn’t show much of anything. 

Observational studies, tracking loosely people’s intake of fats and oils, are underpowered. They’re not able to show a cause of anything by anything. Because these oils are widely believed to be ‘heart healthy’, people who deliberately make healthy lifestyle choices (non-smoking, exercising, stress management, reduced junk food intake, enough sleep, etc.) may choose them more often than other fats. But it’s actually their lifestyle choices keeping them healthy in spite of their oils. 

This is known as the healthy user bias and is a major flaw in this type of research. 

These epidemiological studies allow researchers to spot trends. After hypotheses have been formed, they should be tested with intervention trials. Only then should advice be forthcoming to avoid the embarrassing toing and froing that we see reported daily by the newspapers. Eggs are bad, eggs are good, they’re bad, they’re good, and so on. 

It’s unethical to use humans when scientists believe one group may become ill as a result of the trial. Given the mounting evidence suggesting that high levels of omega-6 PUFAs, especially linoleic acid, are detrimental to health, conducting human research poses an existential moral dilemma. 

This is why Cochrane had such a hard time finding any high-quality evidence for anything except cholesterol lowering.

In the podcast Thinking Nutrition an episode entitled ‘Enough of the “seed oils are toxic” rubbish’, Dr Tim Crowe picks what he thinks is the ‘best evidence’ for the consumption of seed oils. 

He cites the Cochrane study, which we’ve covered, and two others. 

One is observational, so we’ll leave that, but about the other he exclaims, ‘a randomised trial that showed one of the most striking reductions in risk of heart disease, canola oil was used as the primary form of fat!’  

OK everyone, forget it. Eat as much seed oil as you like. 

Unfortunately, Dr Crow didn’t take the time to read the study’s abstract, or indeed the title which is ‘Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease’.  [156] (Emphasis ours).

The canola oil used in this study had been adapted to be low in linoleic acid.

Also, it was deliberately high in alpha-linolenic acid (ALA) which as you know is an omega-3. This paper supports improving the omega-6 to omega-3 ratio by increasing ALA in the diet. 

It’s always worth checking people’s references. 

A two-pronged attack

When it comes to seed oils the dangers are split in a two-pronged attack. 

Firstly, omega-6 PUFAs are vulnerable to oxidation before you even get them home. Then they oxidise further for several reasons we’ve covered. 

Secondly, a high omega-6 to omega-3 ratio seems also to be problematic by increasing chronic inflammation and still more oxidative stress due to the abundance. 

How to get seed oils out of your life

What have you got to lose?

You can spend a lifetime bouncing between studies, but when all is said and done ask yourself this: 

What have I got to lose by lowering my omega-6 PUFAs from junk foods and seed oils? 

Imagine that we were right all along about the dangers of seed oils, and you reduced them. 

Fortunately, you made the necessary changes to your diet. You avoided the oxidative stress and chronic inflammation that ran rampant during the 20th and 21st centuries cutting lives short and writing the scripts to a billion unpublished tragedies. 

You lived to a ripe old age, sprite and healthy right up until the end.   

Now, imagine that we were wrong about seed oils and that they turned out to be inert. 

What did you lose by reducing fried foods in restaurants, and junk foods and swapping seed oils at home for our fruit oils? 

Nothing. 

 

About the author

Tim Rees, BSc mBANT rCNHC, is a registered clinical nutritionist specialising in dietary and lifestyle interventions for chronic diseases. Combining his dual passions of nutrition and history, Tim crafts engaging narratives that breathe life into subjects that might otherwise be considered dry. Operating from his home base in scenic Bavaria, Tim immerses himself in the natural beauty of the surrounding mountains and lakes whenever possible.

References 

[1] Buxton, J. (2021) National life tables – life expectancy in the UK: 2018 to 2020. Office for National Statistics. Available online at: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/lifeexpectancies/bulletins/nationallifetablesunitedkingdom/2018to2020

[2] Walker, J.L., Grint, D.J., Strongman, H. et al. UK prevalence of underlying conditions which increase the risk of severe COVID-19 disease: [ap][aq][ar][as]a point prevalence study using electronic health records. BMC Public Health 21, 484 (2021). https://doi.org/10.1186/s12889-021-10427-2

[3] Department of Health (2012). Report. Long-term conditions compendium of Information: 3rd edition. Available online at: https://www.gov.uk/government/publications/long-term-conditions-compendium-of-information-third-edition Last accessed: 16th May 2023.

[4] Department of Health (2012). Report. Long-term conditions compendium of Information: 3rd edition. Available online at: https://www.gov.uk/government/publications/long-term-conditions-compendium-of-information-third-edition Last accessed: 16th May 2023.

[5] Department of Health (2012). Report. Long-term conditions compendium of Information: 3rd edition. Available online at: https://www.gov.uk/government/publications/long-term-conditions-compendium-of-information-third-edition Last accessed: 16th May 2023.

[6] CDC (2022) Chronic diseases in America. Centers for Disease Control and Prevention. Available online at: https://www.cdc.gov/chronicdisease/resources/infographic/chronic-diseases.htm Last accessed: 16th May 2023.

[7] Oschman J. L. (2011). Chronic disease: are we missing something?. Journal of alternative and complementary medicine (New York, N.Y.), 17(4), 283–285. https://doi.org/10.1089/acm.2011.0101

[8] Chang, C. Y., Ke, D. S., & Chen, J. Y. (2009). Essential fatty acids and human brain. Acta neurologica Taiwanica, 18(4), 231–241.

[9] Moya-Camarena, S. Y., Vanden Heuvel, J. P., Blanchard, S. G., Leesnitzer, L. A., & Belury, M. A. (1999). Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARalpha. Journal of lipid research, 40(8), 1426–1433.

[10] Nixon, H. C. (1930). The Rise of the American Cottonseed Oil Industry. Journal of Political Economy, 38(1), 73–85. http://www.jstor.org/stable/1823218 

[11] WHO (2023) Five billion people unprotected from trans fat leading to heart disease. World Health Organisation. Available online at: https://www.who.int/news/item/23-01-2023-five-billion-people-unprotected-from-trans-fat-leading-to-heart-disease Last accessed: 16th May 2023.

[12] Howell J. D. (2011). Coronary heart disease and heart attacks, 1912-2010. Medical history, 55(3), 307–312. https://doi.org/10.1017/s0025727300005317 

[13] USDA (2018) Food Data Central Search results. U.S Department of Agriculture. Available at: https://fdc.nal.usda.gov/fdc-app.html#/food-details/171024/nutrients Last accessed 15th May 2023.

[14] Our World in Data (2023) Global agricultural land use by major crop type. Our Word in Data. Available at: https://ourworldindata.org/grapher/global-agricultural-land-use-by-major-crop-type?country=Vegetables~Treenuts~Roots+and+Tubers~Pulses~Oilcrops~Fruit~Citrus+Fruit~Cereals~Jute~Oilcrops%2C+Oil+Equivalent Last accessed: 16th May 2023.

[15] Our Word in Data (2023) Land use per kilogram of food product. Our Word in Data. Available at: https://ourworldindata.org/grapher/land-use-per-kg-poore?country=Apples~Bananas~Barley~Berries+%26+Grapes~Brassicas~Cane+Sugar~Cassava~Citrus+Fruit~Groundnuts~Maize~Nuts~Oatmeal~Onions+%26+Leeks~Palm+Oil~Peas~Potatoes~Rapeseed+Oil~Rice~Root+Vegetables~Soybean+Oil~Sunflower+Oil~Tofu+%28soybeans%29~Tomatoes~Wheat+%26+Rye~Other+Fruit~Other+Pulses~Other+Vegetables~Beet+Sugar Last accessed: 16th May 2023.

[16] Our World in Data (2023) Land use for vegetable oil crops, World. Our Word in Data. Available at: https://ourworldindata.org/grapher/land-use-for-vegetable-oil-crops?country=~OWID_WRL Last accessed: 16th May 2023.

[17] Our World in Data (2023) Land use for vegetable oil crops, World. Our Word in Data. Available at: https://ourworldindata.org/grapher/land-use-for-vegetable-oil-crops?country=~OWID_WRL Last accessed: 16th May 2023.

[18] Astrup, A., & Bügel, S. (2019). Overfed but undernourished: recognizing nutritional inadequacies/deficiencies in patients with overweight or obesity. International journal of obesity (2005), 43(2), 219–232. https://doi.org/10.1038/s41366-018-0143-9

[19] Dunford, N (2019) Oil and oilseed processing. Oklahoma State University. Available at: https://extension.okstate.edu/fact-sheets/oil-and-oilseed-processing-i.html# Last accessed: 16th May 2023.

[20] Tao L. Oxidation of polyunsaturated fatty acids and its impact on food quality and human health. Adv Food Technol Nutr Sci Open J. 2015; 1(6): 135-142. doi: 10.17140/AFTNSOJ-1-123

[21] Crosby, G. (2015) Ask the Expert. Harvard School of Chan. Available online: https://www.hsph.harvard.edu/nutritionsource/2015/04/13/ask-the-expert-concerns-about-canola-oil/ Last accessed: 16th May 2023.

[22] WHO (2018) WHO plan to eliminate industrially-produced trans-fatty acids from global food supply. World Health Organisation. Available online:  https://www.who.int/news-room/detail/14-05-2018-who-plan-to-eliminate-industrially-produced-trans-fatty-acids-from-global-food-supply Last accessed: 16th May 2023

[23] Zhang, Q., Qin, W., Lin, D., Shen, Q., & Saleh, A. S. (2015). The changes in the volatile aldehydes formed during the deep-fat frying process. Journal of food science and technology, 52(12), 7683–7696. https://doi.org/10.1007/s13197-015-1923-z

[24] Moumtaz, S., Percival, B.C., Parmar, D. et al. Toxic aldehyde generation in and food uptake from culinary oils during frying practices: peroxidative resistance of a monounsaturate-rich algae oil. Sci Rep 9, 4125 (2019). https://doi.org/10.1038/s41598-019-39767-1

[25] Uchida K. (2000). Role of reactive aldehyde in cardiovascular diseases. Free radical biology & medicine, 28(12), 1685–1696. https://doi.org/10.1016/s0891-5849(00)00226-4 

[26] B. Matthäus, 6 - Oxidation of edible oils, Editor(s): Eric A. Decker, Ryan J. Elias, D. Julian McClements, In Woodhead Publishing Series in Food Science, Technology and Nutrition, Oxidation in Foods and Beverages and Antioxidant Applications, Woodhead Publishing, 2010, Pages 183-238, ISBN 9781845699833, https://doi.org/10.1533/9780857090331.2.183.

[27] GROOTVELD, M., SILWOOD, C.J.L., ADDIS, P., CLAXSON, A., SERRA, B.B. and VIANA, M. (2001), HEALTH EFFECTS OF OXIDIZED HEATED OILS. Foodservice Research International, 13: 41-55. https://doi.org/10.1111/j.1745-4506.2001.tb00028.x

[28] Esfarjani, F, Khoshtinat, K, Zargaraan, A, et al. Evaluating the rancidity and quality of discarded oils in fast food restaurants. Food Sci Nutr. 2019; 7: 2302– 2311. https://doi.org/10.1002/fsn3.1072

[29] USDA (2018) Food data central search results. United States Department of Agriculture. Available at: https://fdc.nal.usda.gov/fdc-app.html#/food-details/171411/nutrients Last accessed: 16th May 2023.

[30] USDA (2013) Deep fat frying and food safety. United States department of Agriculture. Available at: https://www.fsis.usda.gov/food-safety/safe-food-handling-and-preparation/food-safety-basics/deep-fat-frying Last accessed: 16th May 2023.

[31] SFA (2020) Healthier catering tips for chip shops. Food Standards Agency. Available online: https://www.food.gov.uk/business-guidance/healthier-catering-tips-for-chip-shops Last accessed: 16th May 2023.

[32] Nixon, H. C. (1930). The Rise of the American Cottonseed Oil Industry. Journal of Political Economy, 38(1), 73–85. http://www.jstor.org/stable/1823218

[33] Abbott, S. K., Else, P. L., Atkins, T. A., & Hulbert, A. J. (2012). Fatty acid composition of membrane bilayers: importance of diet polyunsaturated fat balance. Biochimica et biophysica acta, 1818(5), 1309–1317. https://doi.org/10.1016/j.bbamem.2012.01.011

[34] Zion Market Research (2018) Cooking Oil Market Size, Share, Growth Report 2030. Zion Market Research Report. Available online at: https://www.zionmarketresearch.com/report/cooking-oil-market Last accessed: 11th May 2023.

[35] Blasbalg, T. L., Hibbeln, J. R., Ramsden, C. E., Majchrzak, S. F., & Rawlings, R. R. (2011). Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. The American journal of clinical nutrition, 93(5), 950–962. https://doi.org/10.3945/ajcn.110.006643

[36] Shahbandeh, M. (2023) Consumption of edible oils in the United States in 2022, by type. Statistica. Available online at: https://www.statista.com/statistics/301044/edible-oils-consumption-united-states-by-type/#:~:text=Soybean%20oil%20has%20the%20highest,metric%20tons%20of%20palm%20oil. Last accessed 11th May 2023.

[37] Chicago Tribune (1990) MCDONALD`S TURNS TO VEGETABLE OIL FOR FRENCH FRIES Available at: https://www.chicagotribune.com/news/ct-xpm-1990-07-24-9003020215-story.html Last accessed: 17th May 2023.

[38] Blume, E. (1987a). Hydrogenation: The food industry’s wild card. Nutrition Action Healthletter, 14(1), 8-9.

[39] Melanie J. Wender, Goodbye Family Farms and Hello Agribusiness: The Story of How Agricultural Policy is Destroying the Family Farm and the Environment, 22 Vill. Envtl. L.J. 141 (2011). Available at: https://digitalcommons.law.villanova.edu/elj/vol22/iss1/6

[40] Oxford Reference (2023) McGovern Committee. Oxford Reference. Available online: https://www.oxfordreference.com/display/10.1093/oi/authority.20110803100144305;jsessionid=FC4AF64B32917C8FC5B1534AF387C6DF Last accessed 17th May 2023.

[41] Burr, G. O., & Burr, M. M. (1973). Nutrition classics from The Journal of Biological Chemistry 82:345-67, 1929. A new deficiency disease produced by the rigid exclusion of fat from the diet. Nutrition reviews, 31(8), 248–249. https://doi.org/10.1111/j.1753-4887.1973.tb06008.x

[42] Spector, A. A., & Kim, H. Y. (2015). Discovery of essential fatty acids. Journal of lipid research, 56(1), 11–21. https://doi.org/10.1194/jlr.R055095 

[43] S.C. Cunnane; P. Guesnet (2011). Linoleic acid recommendations—A house of cards. , 85(6), 0–402. doi:10.1016/j.plefa.2011.09.003

[44] Igarashi, M., Gao, F., Kim, H. W., Ma, K., Bell, J. M., & Rapoport, S. I. (2009). Dietary n-6 PUFA deprivation for 15 weeks reduces arachidonic acid concentrations while increasing n-3 PUFA concentrations in organs of post-weaning male rats. Biochimica et biophysica acta, 1791(2), 132–139. https://doi.org/10.1016/j.bbalip.2008.11.002

[45] Freund, H., Floman, N., Schwartz, B., & Fischer, J. E. (1979). Essential fatty acid deficiency in total parenteral nutrition. Detection by changes in intraocular pressure. Annals of surgery, 190(2), 139–143. https://doi.org/10.1097/00000658-197908000-00003 

[46] Jeppesen, P. B., Christensen, M. S., Høy, C. E., & Mortensen, P. B. (1997). Essential fatty acid deficiency in patients with severe fat malabsorption. The American journal of clinical nutrition, 65(3), 837–843. https://doi.org/10.1093/ajcn/65.3.837

[47] Guesnet, P., Lallemand, S. M., Alessandri, J. M., Jouin, M., & Cunnane, S. C. (2011). α-Linolenate reduces the dietary requirement for linoleate in the growing rat. Prostaglandins, leukotrienes, and essential fatty acids, 85(6), 353–360. https://doi.org/10.1016/j.plefa.2011.08.003

[48] Pot, G. K., Prynne, C. J., Roberts, C., Olson, A., Nicholson, S. K., Whitton, C., Teucher, B., Bates, B., Henderson, H., Pigott, S., Swan, G., & Stephen, A. M. (2012). National Diet and Nutrition Survey: fat and fatty acid intake from the first year of the rolling programme and comparison with previous surveys. The British journal of nutrition, 107(3), 405–415. https://doi.org/10.1017/S0007114511002911

[49] Raatz, S. K., Conrad, Z., & Jahns, L. (2018). Trends in linoleic acid intake in the United States adult population: NHANES 1999-2014. Prostaglandins, leukotrienes, and essential fatty acids, 133, 23–28. https://doi.org/10.1016/j.plefa.2018.04.006

[50] Taha, A.Y. Linoleic acid–good or bad for the brain?. npj Sci Food 4, 1 (2020). https://doi.org/10.1038/s41538-019-0061-9: DiNicolantonio, J. J., & O'Keefe, J. H. (2018). Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis. Open heart, 5(2), e000898. https://doi.org/10.1136/openhrt-2018-000898 

[51] Eilander, A., Harika, R. K., & Zock, P. L. (2015). Intake and sources of dietary fatty acids in Europe: Are current population intakes of fats aligned with dietary recommendations?. European journal of lipid science and technology : EJLST, 117(9), 1370–1377. https://doi.org/10.1002/ejlt.201400513

[52] Stephan J Guyenet , Susan E Carlson, Increase in Adipose Tissue Linoleic Acid of US Adults in the Last Half Century, Advances in Nutrition, Volume 6, Issue 6, November 2015, Pages 660–664, https://doi.org/10.3945/an.115.009944

[53] Tsalamandris, S., Antonopoulos, A. S., Oikonomou, E., Papamikroulis, G. A., Vogiatzi, G., Papaioannou, S., Deftereos, S., & Tousoulis, D. (2019). The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives. European cardiology, 14(1), 50–59. https://doi.org/10.15420/ecr.2018.33.1

[54] Rauber, F., Louzada, M. L. D. C., Martinez Steele, E., Rezende, L. F. M., Millett, C., Monteiro, C. A., & Levy, R. B. (2019). Ultra-processed foods and excessive free sugar intake in the UK: a nationally representative cross-sectional study. BMJ open, 9(10), e027546. https://doi.org/10.1136/bmjopen-2018-027546

[55] Martínez Steele, E., Baraldi, L. G., Louzada, M. L., Moubarac, J. C., Mozaffarian, D., & Monteiro, C. A. (2016). Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ open, 6(3), e009892. https://doi.org/10.1136/bmjopen-2015-009892

[56] Tan, Pei Yee & Teng, Kim-Tiu. (2019). Effects of oxidised oils on inflammation-related cancer risk. Journal of Oil Palm Research. 31. 10.21894/jopr.2019.0007.

[57] Hristov B. D. (2022). The Role of Glutathione Metabolism in Chronic Illness Development and Its Potential Use as a Novel Therapeutic Target. Cureus, 14(9), e29696. https://doi.org/10.7759/cureus.29696

[58] Lang, Calvin. (2001). The Impact of Glutathione on Health and Longevity. Journal of Anti-aging Medicine - J ANTI-AGING MED. 4. 10.1089/10945450152466189.

[59] Martínez Leo, E. E., Peñafiel, A. M., Hernández Escalante, V. M., & Cabrera Araujo, Z. M. (2021). Ultra-processed diet, systemic oxidative stress, and breach of immunologic tolerance. Nutrition (Burbank, Los Angeles County, Calif.), 91-92, 111419. https://doi.org/10.1016/j.nut.2021.111419

[60] Tristan Asensi, M., Napoletano, A., Sofi, F., & Dinu, M. (2023). Low-Grade Inflammation and Ultra-Processed Foods Consumption: A Review. Nutrients, 15(6), 1546. https://doi.org/10.3390/nu15061546

[61] Tortosa-Caparrós, E., Navas-Carrillo, D., Marín, F., & Orenes-Piñero, E. (2017). Anti-inflammatory effects of omega 3 and omega 6 polyunsaturated fatty acids in cardiovascular disease and metabolic syndrome. Critical reviews in food science and nutrition, 57(16), 3421–3429. https://doi.org/10.1080/10408398.2015.1126549

[62] Simopoulos A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 56(8), 365–379. https://doi.org/10.1016/s0753-3322(02)00253-6

[63] Plourde, M., & Cunnane, S. C. (2007). Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 32(4), 619–634. https://doi.org/10.1139/H07-034

[64] Fernandes G. (1994). Dietary lipids and risk of autoimmune disease. Clinical immunology and immunopathology, 72(2), 193–197. https://doi.org/10.1006/clin.1994.1129

[65] DiNicolantonio, J. J., & O'Keefe, J. (2021). The Importance of Maintaining a Low Omega-6/Omega-3 Ratio for Reducing the Risk of Autoimmune Diseases, Asthma, and Allergies. Missouri medicine, 118(5), 453–459.

[66] DiNicolantonio JJ, O’Keefe JH. Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis. Open Heart 2018;5:e000898. doi:10.1136/ openhrt-2018-000898

[67] Jira W, Spiteller G, Carson W, et al. Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients. Chem Phys Lipids 1998;91:1–11.

[68] Parthasarathy S, Litvinov D, Selvarajan K, et al. Lipid peroxidation and decomposition—conflicting roles in plaque vulnerability and stability. Biochim Biophys Acta 2008;1781:221–31; Jira W, Spiteller G, Carson W, et al. Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients. Chem Phys Lipids 1998;91:1–11; Haberland ME, Olch CL, Folgelman AM. Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages. J Biol Chem 1984;259:11305–11.

[69] Belkner J, Wiesner R, Kühn H, et al. The oxygenation of cholesterol esters by the reticulocyte lipoxygenase. FEBS Lett 1991;279:110–4; Brooks CJ, Harland WA, Steel G, et al. Lipids of human atheroma isolation of hydroxyoctade cadienoic acids from advanced aortal lesions. Biochim Biophys Acta 1970;202:563–6; Harland WA, Gilbert JD, Steel G, et al. Lipids of human atheroma. The occurrence of a new group of polar sterol esters in various stages of human atherosclerosis. Atherosclerosis 1971;13:239–46.

[70] Belkner J, Wiesner R, Kühn H, et al. The oxygenation of cholesterol esters by the reticulocyte lipoxygenase. FEBS Lett 1991;279:110–4.

[71] Bemelmans WJ, Lefrandt JD, Feskens EJ, et al. Increased alpha linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. Eur J Clin Nutr 2004;58:1083–9.

[72] Bemelmans WJ, Broer J, Feskens EJ, et al. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-Linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Am J Clin Nutr 2002;75:221–7.

[73] Palmer, A. J., Blacket, R. B., & Leelarthaepin, B. (1973). Hyperlipidaemia in a group of coronary subjects in Sydney. The Medical journal of Australia, 2(1), 19–23.

[74] Ramsden CE, Zamora D, Leelarthaepin B, et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013;346:e8707.

[75] Jones, C. W., Handler, L., Crowell, K. E., Keil, L. G., Weaver, M. A., & Platts-Mills, T. F. (2013). Non-publication of large randomized clinical trials: cross sectional analysis. BMJ (Clinical research ed.), 347, f6104. https://doi.org/10.1136/bmj.f6104

[76] Frantz ID Jr, Keys A. R01 HE 0986-03 Research Grant Application: Effect of a Dietary Change on Human Cardiovascular Disease “The Minnesota Coronary Survey”. 1967.http://www.add.lib.iastate.edu/spcl/manuscripts/MS576.html 

[77] Ramsden CE, Zamora D, Majchrzak-Hong S, et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ 2016;353:i1246.

[78] DiNicolantonio JJ, O’Keefe JH. Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis. Open Heart 2018;5:e000898. doi:10.1136/ openhrt-2018-000898

[79] Simopoulos A. P. (2016). An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients, 8(3), 128. https://doi.org/10.3390/nu8030128

[80] Ades, P. A., & Savage, P. D. (2017). Obesity in coronary heart disease: An unaddressed behavioral risk factor. Preventive medicine, 104, 117–119. https://doi.org/10.1016/j.ypmed.2017.04.013

[81] Mitchell, N. S., Catenacci, V. A., Wyatt, H. R., & Hill, J. O. (2011). Obesity: overview of an epidemic. The Psychiatric clinics of North America, 34(4), 717–732. https://doi.org/10.1016/j.psc.2011.08.005

[82] Shan Z, Rehm CD, Rogers G, et al. Trends in Dietary Carbohydrate, Protein, and Fat Intake and Diet Quality Among US Adults, 1999-2016. JAMA. 2019;322(12):1178–1187. doi:10.1001/jama.2019.13771

[83] Simopoulos A. P. (2016). An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients, 8(3), 128. https://doi.org/10.3390/nu8030128

[84] Ambreen, G., Siddiq, A. & Hussain, K. Association of long-term consumption of repeatedly heated mix vegetable oils in different doses and hepatic toxicity through fat accumulation. Lipids Health Dis 19, 69 (2020). https://doi.org/10.1186/s12944-020-01256-0

[85] Santoro, N., Caprio, S., & Feldstein, A. E. (2013). Oxidized metabolites of linoleic acid as biomarkers of liver injury in nonalcoholic steatohepatitis. Clinical lipidology, 8(4), 411–418. https://doi.org/10.2217/clp.13.39

[86] Amandeep K. Sahota, Warren L. Shapiro, Kimberly P. Newton, Steven T. Kim, Joanie Chung, Jeffrey B. Schwimmer; Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009–2018. Pediatrics December 2020; 146 (6): e20200771. 10.1542/peds.2020-0771

[87] Pilar Guallar-Castillón and others, Intake of fried foods is associated with obesity in the cohort of Spanish adults from the European Prospective Investigation into Cancer and Nutrition, The American Journal of Clinical Nutrition, Volume 86, Issue 1, July 2007, Pages 198–205,

[88] Shoeb, M., Ansari, N. H., Srivastava, S. K., & Ramana, K. V. (2014). 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Current medicinal chemistry, 21(2), 230–237. https://doi.org/10.2174/09298673113209990181

[89] Mattson M. P. (2009). Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Experimental gerontology, 44(10), 625–633. https://doi.org/10.1016/j.exger.2009.07.003

[90] Shoeb, M., Ansari, N. H., Srivastava, S. K., & Ramana, K. V. (2014). 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Current medicinal chemistry, 21(2), 230–237. https://doi.org/10.2174/09298673113209990181

[91] Poli, G., Schaur, R. J., Siems, W. G., & Leonarduzzi, G. (2008). 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest. Medicinal research reviews, 28(4), 569–631. https://doi.org/10.1002/med.20117

[92] Nishikawa, A., Sodum, R., & Chung, F. L. (1992). Acute toxicity of trans-4-hydroxy-2-nonenal in Fisher 344 rats [corrected]. Lipids, 27(1), 54–58. https://doi.org/10.1007/BF02537060

[93] Wonisch, W., Zellnig, G., Kohlwein, S.D., Schaur, R.J., Bilinski, T., Tatzber, F. and Esterbauer, H. (2001), Ultrastructural analysis of HNE-treated Saccharomyces cerevisiae cells reveals fragmentation of the vacuole and an accumulation of lipids in the cytosol. Cell Biochem. Funct., 19: 59-64. https://doi.org/10.1002/cbf.888

[94] Singh, S. P., Niemczyk, M., Saini, D., Awasthi, Y. C., Zimniak, L., & Zimniak, P. (2008). Role of the electrophilic lipid peroxidation product 4-hydroxynonenal in the development and maintenance of obesity in mice. Biochemistry, 47(12), 3900–3911. https://doi.org/10.1021/bi702124u

[95]Guyenet, S. J., & Carlson, S. E. (2015). Increase in adipose tissue linoleic acid of US adults in the last half century. Advances in nutrition (Bethesda, Md.), 6(6), 660–664. https://doi.org/10.3945/an.115.009944

[96] https://animalsystemsbiology.cfans.umn.edu/sites/animalsystemsbiology.cfans.umn.edu/files/files/csallany-2015-jaocs_92-1413-1419.pdf

[97] Moon, R. J., Harvey, N. C., Robinson, S. M., Ntani, G., Davies, J. H., Inskip, H. M., Godfrey, K. M., Dennison, E. M., Calder, P. C., Cooper, C., & SWS Study Group (2013). Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. The Journal of clinical endocrinology and metabolism, 98(1), 299–307. https://doi.org/10.1210/jc.2012-2482

[98] Hernández ML, Sicardo MD, Belaj A and Martínez-Rivas JM (2021) The Oleic/Linoleic Acid Ratio in Olive (Olea europaea L.) Fruit Mesocarp Is Mainly Controlled by OeFAD2-2 and OeFAD2-5 Genes Together With the Different Specificity of Extraplastidial Acyltransferase Enzymes. Front. Plant Sci. 12:653997. doi: 10.3389/fpls.2021.653997

[99] Galvão Cândido, F., Xavier Valente, F., da Silva, L. E., Gonçalves Leão Coelho, O., Gouveia Peluzio, M. D. C., & Gonçalves Alfenas, R. C. (2018). Consumption of extra virgin olive oil improves body composition and blood pressure in women with excess body fat: a randomized, double-blinded, placebo-controlled clinical trial. European journal of nutrition, 57(7), 2445–2455. https://doi.org/10.1007/s00394-017-1517-9

[100] Nigam, P., Bhatt, S., Misra, A., Chadha, D. S., Vaidya, M., Dasgupta, J., & Pasha, Q. M. (2014). Effect of a 6-month intervention with cooking oils containing a high concentration of monounsaturated fatty acids (olive and canola oils) compared with control oil in male Asian Indians with nonalcoholic fatty liver disease. Diabetes technology & therapeutics, 16(4), 255–261. https://doi.org/10.1089/dia.2013.0178

[101] Deol   P, Evans   JR, Dhahbi   J, et al.   Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: potential role for the liver. PloS One.  2015;10(7):e0132672.

[102] Clatici, V. G., Voicu, C., Voaides, C., Roseanu, A., Icriverzi, M., & Jurcoane, S. (2018). Diseases of Civilization - Cancer, Diabetes, Obesity and Acne - the Implication of Milk, IGF-1 and mTORC1. Maedica, 13(4), 273–281. https://doi.org/10.26574/maedica.2018.13.4.273

[103] Deol   P, Fahrmann   J, Yang   J, et al.   Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice. Sci Rep.  2017;7(1):12488.

[104] Poonamjot Deol and others, Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice, Endocrinology, Volume 161, Issue 2, February 2020, bqz044, https://doi.org/10.1210/endocr/bqz044

[105] Klement, J., Ott, V., Rapp, K., Brede, S., Piccinini, F., Cobelli, C., Lehnert, H., Hallschmid, M., (2017). "Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men." Diabetes, 66(2): 264-271; Lawson, E.A., (2017). "The effects of oxytocin on eating behaviour and metabolism in humans." Nature Reviews Endocrinology, 13: 700–709; Zhang, H., Wu, C., Chen, Q., Chen, X., Xu, Z., Wu, J., Cai, D., (2013). "Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models." PLoS One, 8(5): e61477; Blevins, J.E., Ho, J.M., (2013). "Role of oxytocin signaling in the regulation of body weight." Reviews in Endocrine and Metabolic Disorders, 14(4): 311–329.

[106] University of California - Riverside. "America's most widely consumed oil causes genetic changes in the brain: Soybean oil linked to metabolic and neurological changes in mice." ScienceDaily. ScienceDaily, 17 January 2020. <www.sciencedaily.com/releases/2020/01/200117080827.htm>.

[107] Pringles (2023) Pringles UK. Available at: https://www.pringles.com/centraleurope/en/products/flavours/pringles-original-200g.html#:~:text=INGREDIENTS%3A%20Dehydrated%20potatoes%2C%20vegetable%20oils,%2C%20colour%20(annatto%20norbixin). Last accessed: 26th May 2023.

[108] Pingles (2023) Pringles (US). Available online: https://www.pringles.com/en-us/products/pringles-the-original-product.html#:~:text=DRIED%20POTATOES%2C%20VEGETABLE%20OIL%20(CORN,DIGLYCERIDES%2C%20SALT%2C%20WHEAT%20STARCH. Last accessed: 26th May 2023.

[109] Sam, A. H., Salem, V., & Ghatei, M. A. (2011). Rimonabant: From RIO to Ban. Journal of obesity, 2011, 432607. https://doi.org/10.1155/2011/432607

[110] Alvheim, A. R., Torstensen, B. E., Lin, Y. H., Lillefosse, H. H., Lock, E. J., Madsen, L., Frøyland, L., Hibbeln, J. R., & Malde, M. K. (2014). Dietary linoleic acid elevates the endocannabinoids 2-AG and anandamide and promotes weight gain in mice fed a low fat diet. Lipids, 49(1), 59–69. https://doi.org/10.1007/s11745-013-3842-y

[111] Simopoulos A. P. (2016). An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients, 8(3), 128. https://doi.org/10.3390/nu8030128

[112] Dighriri, I. M., Alsubaie, A. M., Hakami, F. M., Hamithi, D. M., Alshekh, M. M., Khobrani, F. A., Dalak, F. E., Hakami, A. A., Alsueaadi, E. H., Alsaawi, L. S., Alshammari, S. F., Alqahtani, A. S., Alawi, I. A., Aljuaid, A. A., & Tawhari, M. Q. (2022). Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review. Cureus, 14(10), e30091. https://doi.org/10.7759/cureus.30091

[113] Brenna J. T. (2016). Arachidonic acid needed in infant formula when docosahexaenoic acid is present. Nutrition reviews, 74(5), 329–336. https://doi.org/10.1093/nutrit/nuw007

[114] Loef, M., & Walach, H. (2013). The omega-6/omega-3 ratio and dementia or cognitive decline: a systematic review on human studies and biological evidence. Journal of nutrition in gerontology and geriatrics, 32(1), 1–23. https://doi.org/10.1080/21551197.2012.752335

[115] Fan, R., Zhao, L., Ding, B. J., Xiao, R., & Ma, W. W. (2021). The association of blood non-esterified fatty acid, saturated fatty acids, and polyunsaturated fatty acids levels with mild cognitive impairment in Chinese population aged 35-64 years: a cross-sectional study. Nutritional neuroscience, 24(2), 148–160. https://doi.org/10.1080/1028415X.2019.1610606

[116] Berger, M., Smesny, S., Kim, SW. et al. Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study. Transl Psychiatry 7, e1220 (2017). https://doi.org/10.1038/tp.2017.190

[117] Dam, H., Nielsen, G. K., Prange, I. & Sondergaard, E. Influence of linoleic and linolenic acids on symptoms of vitamin E deficiency in chicks. Nature 182, 802–803 (1958); Fischer, V. W. & Nelson, J. S. Cerebrovascular changes in tocopherol-depleted chicks, fed linoleic acid. J. Neuropathol. Exp. Neurol. 32, 474–483 (1973); Bartov, I. & Bornstein, S. Susceptibility of chicks to nutritional encephalopathy: effect of fat and alpha-tocopherol content of the breeder diet. Poult. Sci. 59, 264–267 (1980); Dam, H. & Sondergaard, E. The encephalomalacia producing effect of arachidonic and linoleic acids. Z. Ernahrungswiss 2, 217–222 (1962); Budowski, P., Bartov, I., Dror, Y. & Frankel, E. N. Lipid oxidation products and chick nutritional.

[118] Taha, A.Y. Linoleic acid–good or bad for the brain?. npj Sci Food 4, 1 (2020). https://doi.org/10.1038/s41538-019-0061-9

[119] Taha, A.Y. Linoleic acid–good or bad for the brain?. npj Sci Food 4, 1 (2020). https://doi.org/10.1038/s41538-019-0061-9

[120] Putnam, J. C., Carlson, S. E., DeVoe, P. W. & Barness, L. A. The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. Am. J. Clin. Nutr. 36, 106–114 (1982).

[121] Jenness R. (1979). The composition of human milk. Seminars in perinatology, 3(3), 225–239.

[122] Hansen, A. E., Haggard, M. E., Boelsche, A. N., Adam, D. J. & Wiese, H. F. Essential fatty acids in infant nutrition. III. Clinical manifestations of linoleic acid deficiency. J. Nutr. 66, 565–576 (1958).

[123] Bernard, J. Y., Armand, M., Garcia, C., Forhan, A., De Agostini, M., Charles, M. A., Heude, B., & EDEN Mother-Child Cohort Study Group (2015). The association between linoleic acid levels in colostrum and child cognition at 2 and 3 y in the EDEN cohort. Pediatric research, 77(6), 829–835. https://doi.org/10.1038/pr.2015.50

[124] Bernard, J. Y., Armand, M., Peyre, H., Garcia, C., Forhan, A., De Agostini, M., Charles, M. A., Heude, B., & EDEN Mother-Child Cohort Study Group (Etude des Déterminants pré- et postnatals précoces du développement et de la santé de l'Enfant) (2017). Breastfeeding, Polyunsaturated Fatty Acid Levels in Colostrum and Child Intelligence Quotient at Age 5-6 Years. The Journal of pediatrics, 183, 43–50.e3. https://doi.org/10.1016/j.jpeds.2016.12.039

[125] Lassek, W. D., & Gaulin, S. J. (2014). Linoleic and docosahexaenoic acids in human milk have opposite relationships with cognitive test performance in a sample of 28 countries. Prostaglandins, leukotrienes, and essential fatty acids, 91(5), 195–201. https://doi.org/10.1016/j.plefa.2014.07.017

[126] Steenweg-de Graaff, J., Tiemeier, H., Ghassabian, A., Rijlaarsdam, J., Jaddoe, V. W., Verhulst, F. C., & Roza, S. J. (2016). Maternal Fatty Acid Status During Pregnancy and Child Autistic Traits: The Generation R Study. American journal of epidemiology, 183(9), 792–799. https://doi.org/10.1093/aje/kwv263

[127] Kim, H., Kim, H., Lee, E., Kim, Y., Ha, E. H., & Chang, N. (2017). Association between maternal intake of n-6 to n-3 fatty acid ratio during pregnancy and infant neurodevelopment at 6 months of age: results of the MOCEH cohort study. Nutrition journal, 16(1), 23. https://doi.org/10.1186/s12937-017-0242-9

[128] Taha, A.Y. Linoleic acid–good or bad for the brain?. npj Sci Food 4, 1 (2020). https://doi.org/10.1038/s41538-019-0061-9

[129] Ramsden, C. E. et al. Targeted alterations in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache: a secondary analysis of a randomized trial. Pain 156, 587–596 (2015).

[130] Shinto, Lynne & Raber, Jacob & Mishra, Anusha & Roese, Natalie & Silbert, Lisa. (2022). A Review of Oxylipins in Alzheimer’s Disease and Related Dementias (ADRD): Potential Therapeutic Targets for the Modulation of Vascular Tone and Inflammation. Metabolites. 12. 826. 10.3390/metabo12090826.

[131] Dayton, S., & Pearce, M. L. (1969). A Controlled Clinical Trial of a Diet High in Unsaturated Fat in Preventing Complications of Atherosclerosis. Circulation; 40:II-1–II-63 https://doi.org/10.1161/01.CIR.40.1S2.II-1

[132] Pearce, M. L., & Dayton, S. (1971). Incidence of cancer in men on a diet high in polyunsaturated fat. Lancet (London, England), 1(7697), 464–467. https://doi.org/10.1016/s0140-6736(71)91086-5

[133] Bueno-de-Mesquita, H. B. Highlights of the International conference on food factors (ICoFF): chemistry and prevention, Hamamatsu, Japan. Eur. J. Cancer Prey., 5: 209-215, 1995. 6. Noguchi, M., Rose, D. P., Earashi, M., and Miyazaki, I. The role of fatty acids and eicosanoid synthesis inhibitors in breast carcinoma. Oncology (Basel), 52: 265-271, 1995.

[134] Rose, D. P., Connolly, J. M., & Liu, X. H. (1994). Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. Cancer research, 54(24), 6557–6562.

[135] Rong Jin, Jiaqing Hao, Yanmei Yi, Di Yin, Yuan Hua, Xiaohong Li, Hanmei Bao, Xianlin Han, Nejat K. Egilmez, Edward R. Sauter, Bing Li; Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing E-FABP–Mediated Mitochondrial Dysfunction. Cancer Res 15 October 2021; 81 (20): 5296–5310. https://doi.org/10.1158/0008-5472.CAN-21-0757

[136] Hsu, C. C., Tseng, L. M., & Lee, H. C. (2016). Role of mitochondrial dysfunction in cancer progression. Experimental biology and medicine (Maywood, N.J.), 241(12), 1281–1295. https://doi.org/10.1177/1535370216641787

[137] Alexis Diaz-Vegas and others, Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?, Endocrine Reviews, Volume 41, Issue 3, June 2020, bnaa005, https://doi.org/10.1210/endrev/bnaa005

[138] López-García, P., & Moreira, D. (2020). The Syntrophy hypothesis for the origin of eukaryotes revisited. Nature microbiology, 5(5), 655-667.

[139] Huiyong Yin & Mingjiang Zhu (2012) Free radical oxidation of cardiolipin: chemical mechanisms, detection and implication in apoptosis, mitochondrial dysfunction and human diseases, Free Radical Research, 46:8, 959-974, DOI: 10.3109/10715762.2012.676642

[140] Schuster, S., Johnson, C. D., Hennebelle, M., Holtmann, T., Taha, A. Y., Kirpich, I. A., Eguchi, A., Ramsden, C. E., Papouchado, B. G., McClain, C. J., & Feldstein, A. E. (2018). Oxidized linoleic acid metabolites induce liver mitochondrial dysfunction, apoptosis, and NLRP3 activation in mice. Journal of lipid research, 59(9), 1597–1609. https://doi.org/10.1194/jlr.M083741

[141] Lazic M., Inzaugarat M. E., Povero D., Zhao I. C., Chen M., Nalbandian M., Miller Y. I., Chernavsky A. C., Feldstein A. E., and Sears D. D.. 2014. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis. PLoS One. 9: e107658.

[142] Ramsden C. E., Ringel A., Feldstein A. E., Taha A. Y., MacIntosh B. A., Hibbeln J. R., Majchrzak-Hong S. F., Faurot K. R., Rapoport S. I., Cheon Y., et al.. 2012. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot. Essent. Fatty Acids. 87: 135–141.

[143] Yamashima, T., Mori, Y., Seike, T., Ahmed, S., Boontem, P., Li, S., Oikawa, S., Kobayashi, H., Yamashita, T., Kikuchi, M., Kaneko, S., & Mizukoshi, E. (2023). Vegetable Oil-Peroxidation Product 'Hydroxynonenal' Causes Hepatocyte Injury and Steatosis via Hsp70.1 and BHMT Disorders in the Monkey Liver. Nutrients, 15(8), 1904. https://doi.org/10.3390/nu15081904

[144] Stephan J Guyenet , Susan E Carlson, Increase in Adipose Tissue Linoleic Acid of US Adults in the Last Half Century, Advances in Nutrition, Volume 6, Issue 6, November 2015, Pages 660–664, https://doi.org/10.3945/an.115.009944

[145] Feng, J., Wang, Y., Li, W., Zhao, Y., Liu, Y., Yao, X., Liu, S., Yu, P., & Li, R. (2022). High levels of oxidized fatty acids in HDL impair the antioxidant function of HDL in patients with diabetes. Frontiers in endocrinology, 13, 993193. https://doi.org/10.3389/fendo.2022.993193

[146] Rader D. J. (2007). Mechanisms of disease: HDL metabolism as a target for novel therapies. Nature clinical practice. Cardiovascular medicine, 4(2), 102–109. https://doi.org/10.1038/ncpcardio0768

[147] Ramsden, C. E., Ringel, A., Feldstein, A. E., Taha, A. Y., MacIntosh, B. A., Hibbeln, J. R., Majchrzak-Hong, S. F., Faurot, K. R., Rapoport, S. I., Cheon, Y., Chung, Y. M., Berk, M., & Mann, J. D. (2012). Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins, leukotrienes, and essential fatty acids, 87(4-5), 135–141. https://doi.org/10.1016/j.plefa.2012.08.004

[148] Wei, D., Li, J., Shen, M., Jia, W., Chen, N., Chen, T., Su, D., Tian, H., Zheng, S., Dai, Y., & Zhao, A. (2010). Cellular production of n-3 PUFAs and reduction of n-6-to-n-3 ratios in the pancreatic beta-cells and islets enhance insulin secretion and confer protection against cytokine-induced cell death. Diabetes, 59(2), 471–478. https://doi.org/10.2337/db09-0284

[149] Calder, P. C., & Deckelbaum, R. J. (2014). Dietary fatty acids in health and disease: greater controversy, greater interest. Current opinion in clinical nutrition and metabolic care, 17(2), 111–115. https://doi.org/10.1097/MCO.0000000000000038

[150] Hooper L, Al‐Khudairy L, Abdelhamid AS, Rees K, Brainard JS, Brown TJ, Ajabnoor SM, O'Brien AT, Winstanley LE, Donaldson DH, Song F, Deane KHO. Omega‐6 fats for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD011094. DOI: 10.1002/14651858.CD011094.pub4. Accessed 26 May 2023.

[151] Farvid M.S., Ding M., Pan A., Sun Q., Chiuve S.E., Steffen L.M., Willett W.C., Hu F.B. Dietary linoleic acid and risk of coronary heart disease: A systematic review and meta-analysis of prospective cohort studies. Circulation. 2014;130:1568–1578. doi: 10.1161/CIRCULATIONAHA.114.010236.

[152] Marklund, M., Wu, J. H. Y., Imamura, F., Del Gobbo, L. C., Fretts, A., de Goede, J., Shi, P., Tintle, N., Wennberg, M., Aslibekyan, S., Chen, T. A., de Oliveira Otto, M. C., Hirakawa, Y., Eriksen, H. H., Kröger, J., Laguzzi, F., Lankinen, M., Murphy, R. A., Prem, K., Samieri, C., … Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE) (2019). Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality. Circulation, 139(21), 2422–2436. https://doi.org/10.1161/CIRCULATIONAHA.118.038908

[153] Li, J., Guasch-Ferré, M., Li, Y., & Hu, F. B. (2020). Dietary intake and biomarkers of linoleic acid and mortality: systematic review and meta-analysis of prospective cohort studies. The American journal of clinical nutrition, 112(1), 150–167. https://doi.org/10.1093/ajcn/nqz349

[154] Wu, Jason & Marklund, Matti & Imamura, Fumiaki & Tintle, Nathan & Korat, Andres & de Goede, Janette & Zhou, Xia & Yang, Wei-Sin & Otto, Marcia & Kröger, Janine & Qureshi, Waqas & Virtanen, Jyrki & Bassett, Julie & Frazier-Wood, Alexis & Lankinen, Maria & Murphy, Rachel & Rajaobelina, Kalina & Gobbo, Liana & Forouhi, Nita & Mozaffarian, Dariush. (2017). Omega-6 fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. The Lancet Diabetes & Endocrinology. 5. 10.1016/S2213-8587(17)30307-8.

[155] Hooper L, Al‐Khudairy L, Abdelhamid AS, Rees K, Brainard JS, Brown TJ, Ajabnoor SM, O'Brien AT, Winstanley LE, Donaldson DH, Song F, Deane KHO. Omega‐6 fats for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD011094. DOI: 10.1002/14651858.CD011094.pub4. Accessed 26 May 2023.

[156] de Lorgeril, M., Renaud, S., Mamelle, N., Salen, P., Martin, J. L., Monjaud, I., Guidollet, J., Touboul, P., & Delaye, J. (1994). Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet (London, England), 343(8911), 1454–1459. https://doi.org/10.1016/s0140-6736(94)92580-1