In November 1978, a six-year-old girl was admitted to hospital with a serious gunshot wound to the chest. Gravely injured, she underwent a long series of operations to repair the damage to her abdomen. More than three meters of her gastrointestinal tract had to be removed. For months she was unable to digest food. To prevent malnutrition, her doctors put her on a regimen of total parenteral nutrition (TPN), a form of liquid sustenance injected directly into the bloodstream1.
At that time in America, it was common for TPN to contain chiefly carbohydrate in the form of sugar, a small amount of protein and zero fat. But clinicians had begun to realize that patients fed such a diet would eventually experience essential fatty acid (EFA) deficiency, showing symptoms such as rashes and hair loss2.
Doctors in the late 70s had experimented with supplementing TPN with essential fatty acids, replacing a portion of the calories from sugar with calories from a dietary fat called linoleic acid. Linoleic acid is an essential omega-6 fatty acid. It is essential in the sense that without a dietary source of linoleic acid, normal growth and development is impossible. The importance of linoleic acid to cell function had been determined by a large amount of research beginning in the late 1920s3. The name omega-6 refers to the molecular structure of the fat, with a carbon double bond in the sixth position counting from the end of the molecule.
Several trials had been run using TPN supplemented with an emulsion of soybean oil, about 42% of which is linoleic acid1. The new solution appeared to prevent essential fatty acid deficiency in patients on long-term TPN4.
The hospital of the six-year-old gunshot victim used a different form of fat-supplemented TPN — one made with safflower oil rather than soybean oil. Safflower oil is around 76% linoleic acid1, considerably higher than soybean oil. Because introducing a source of linoleic acid into the diet was the purpose of supplementing the TPN with fat in the first place, the substitution of one preparation for the other caused no concern1.
A troubling mystery
For five months, as she recovered from serious surgery, the young patient was given daily TPN supplemented with safflower oil. Gradually, the she began to experience troubling neurological symptoms. First she complained of numbness on the bottom of her feet. The numbness spread to encompass her lower legs, accompanied by a dull pain. She experienced episodes of weakness so severe she couldn’t walk. Her eyesight became blurred. The symptoms were rare at first, but became more and more frequent over time and eventually occurred almost every day1.
In January 1980, the girl was admitted to hospital for a neurological exam. Her results for almost every test were normal. There was no obvious cause for the frightening, escalating series of symptoms she had experienced.
Blood tests did show a marginal level of linoleic acid deficiency, but that seemed a very unlikely cause; even in cases of much more extreme essential fatty acid deficiency in patients given fat-free TPN, there were no reports of neurological problems.
However, the blood tests also detected another abnormality: levels of alpha-Linolenic (note the extra ‘n’) fatty acid were undetectably low, whereas in healthy children they account for about 0.2% of plasma lipid volume1.
Alpha-Linolenic acid (ALA) is an omega-3 fatty acid. (Omega-3 fats have a carbon double bond in the third position, counting from the end of the molecule.) It was first isolated around the same time as the discovery of linoleic acid. But while the biological necessity of linoleic acid was well established, there was no such consensus on the essential nature of ALA. A paper published in 1979 begins “Linolenic acid (ALA) deficiency has not been demonstrated clearly in warm blooded animals”5.
Soybean oil naturally contains about 7% ALA1. Safflower oil, on the other hand, contains around 0.7%1, about 10 times less. Patients given soybean oil to supplement their intake of linoleic acid had also inadvertently been receiving ALA.
A novel solution
Although there was no conclusive medical evidence that ALA deficiency could cause the neurological symptoms the girl was experiencing (or indeed any other symptoms), in February her doctors switched her TPN back to a soybean oil preparation. Over the next 12 weeks, her neurological problems gradually but completely disappeared1.
It seemed medically plausible that the ALA deficiency was the root cause of the symptoms the girl had experienced. Omega-3 fatty acids derived from ALA were known to exist in unusually high proportions in brain and retina cells1, which might explain her neurological and visual problems.
But the question remained: if a lack of ALA was the problem, why did patients on long-term TPN with no fat supplementation of any kind not experience the same neurological problems? Such patients would be deficient in linoleic acid and ALA.
The reason, clinicians deduced, was that the presence of linoleic acid in the diet actively decreased the conversion of ALA into other metabolically essential omega-3 fatty acids. As early as 1968, scientists had determined there were “inhibitions and competitions” between omega-6 and omega-3 fatty acids in rats. It seemed likely that the two fatty acids were processed by the same enzymes6.
In the case of the young gunshot victim, her doctors reasoned that a high level of linoleic acid, combined with a marginal intake of ALA, had actively suppressed the processing of what little ALA the patient had available, resulting in the severe symptoms. In other words, what was important was not just the absolute quantities of linoleic acid and ALA consumed, but the relative ratio between the amounts. The ratio of linoleic acid to ALA in soybean oil is around 6:1. The same ratio in safflower oil is 115:11.The importance of the omega-6:omega-3 ratio has been reinforced by later research78910.
In the 30 years since the first reported case of ALA deficiency in a person, the role of omega-3 fatty acids in human health has the been the subject of vast quantities of research. As with many areas of human nutrition, the results are often contradictory and require careful interpretation.
Research in 2002 suggested that, while for much of our history humans had eaten a diet with an omega-6:omega-3 ratio of between 1:1 and 3:1, the modern diet in Western developed countries was closer to 15:111. This ratio is attributable to a number of factors: high consumption of vegetable fats (e.g. soybean oil, sunflower oil, corn oil etc.) which are typically high in linoleic acid and low in ALA; the feeding of high-cereal diets to animals raised for food, reducing the quantity of omega-3 fats in their meat12, milk13 and eggs14; and the fact that domesticated species of even non-cereal plants often have lower amounts of omega-3 fats than their wild counterparts11.
Changing a person’s ratio of omega-6 to omega-3 fatty acids can be brought about in three ways: increasing the amount of omega-3 fats they consume (either by changing their diet or adding an omega-3 supplement); decreasing the amount of omega-6 fats they consume (e.g. by consuming less vegetable oil); or doing both simultaneously. In clinical intervention trials, adding an omega-3 supplement seems to be the most common approach, as it is both easy for the subject to adhere to and simple for the clinician to quantify.
Increasing intake of omega-3 fatty acids has been indicated to reduce the risk of an impressive array of ailments, particularly depression15, cognitive decline16 and cardiovascular disease17. Generally, reducing the ratio of omega-6 to omega-3 consumption is thought to reduce inflammation and chronic diseases that “involve inflammatory processes”18.
In the case of each health claim, the accumulation of medical evidence does not meet the bar of “conclusive”. Reasonable people can disagree over the particular benefits of omega-3 consumption above the level required to ward off severe deficiency. But what is clear is that, if omega-3 consumption does yield protection against disease, the concurrent level of omega-6 consumption plays an important role in that process. And omega-6 fatty acids are so ubiquitous in the diet of Western developed nations that avoiding a herculean dose is extremely difficult.
Which is why it’s so acutely, distressingly baffling that so many popular omega-3 supplements include a side-order of omega-6 fatty acids. An Amazon.com search for the term Omega 3-6-9 returns over 5000 results.
Such products claim to provide a “full spectrum” of omega-3, omega-6 and omega-9 fats. (Omega-9 fatty acids are another ubiquitous component of many vegetable oils, and are not considered essential fatty acids to begin with. They also compete for the same enzymes as omega-3 fats19.) The marketing logic is clear and devious: if omega-3 fatty acids are healthy, then a complete dose of all the omega fatty acids must be even healthier.
Consider the popular offering from Now Foods: for every 900mg of omega-3, it provides 880mg of omega-6 and omega-9 fatty acids. Or the top-ranked Amazon seller from Nordic Naturals, which provides 489mg of omega-6 and omega-9 for every 565mg of omega-3.
In such products, the additional omega-6 and omega-9 simply contribute to the vast existing dietary surfeit of those fats in the overwhelming majority of people. In the best-case scenario, the additional omega-6 and omega-9 fatty acids are singularly useless. In the worst case, “full spectrum” fats decrease the effectiveness of the supplemented omega-3 by competing for the same metabolic enzymes.
The lack of omega-3 fats in the modern Western diet can be partially explained by the expense of the richest source of the fatty acid: wild fish. By way of comparison, omega-6 fats can be found in the most modest foodstuffs: potato chips, french fries, margarine, cakes, ice-cream — in fact, the majority of all processed foods will contain some level of vegetable fat and thus some quantity of omega-6.
No-one needs any more of this stuff than they’re already eating. The fact that the presence of other omega fats can undermine the activity of omega-3 simply underscores the point: taking a supplement containing omega-6 is a bad idea.
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- A case of human linolenic acid deficiency involving neurological abnormalities [↩] [↩] [↩] [↩] [↩] [↩] [↩] [↩] [↩] [↩] [↩]
- Essential fatty acid deficiency during total parenteral nutrition [↩]
- Essential Fatty Acids [↩]
- The effect of fat emulsion (intralipid) on essential fatty acid deficiency in infants receiving intravenous alimentation [↩]
- Linolenic acid deficiency [↩]
- Essential fatty acids reinvestigated [↩]
- How relevant is the ratio of dietary n-6 to n-3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study [↩]
- Effect of n-3 oral supplements on the n-6/n-3 ratio in young adults [↩]
- Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes [↩]
- Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women [↩]
- The importance of the ratio of omega-6/omega-3 essential fatty acids [↩] [↩]
- Fatty acid ratios in free-living and domestic animals [↩]
- Effects of feeding increasing dietary levels of high oleic or regular sunflower or linseed oil on fatty acid profile of goat milk [↩]
- Egg yolk as a source of long-chain polyunsaturated fatty acids in infant feeding [↩]
- Updated systematic review and meta-analysis of the effects of n−3 long-chain polyunsaturated fatty acids on depressed mood [↩]
- Current evidence for the clinical use of long-chain polyunsaturated N-3 Fatty acids to prevent age-related cognitive decline and Alzheimer’s disease [↩]
- α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis [↩]
- Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids [↩]
- Essential polyunsaturated fatty acids, inflammation, atherosclerosis and cardiovascular diseases [↩]