11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

PREMIUM

How Essential Are the Essential Fatty Acids?

My 2008 Special Report, updated with some new reflections.

Chris Masterjohn, PhD

1
29 min ago

I wrote this Special Report in 2008. Ordinarily reserved for Masterpass members, it is is
free for everyone today only. Learn more about the Masterpass here.

I believe this knowledge is well worth taking in now, 14 years later. I have included
updates and reflections below.

My original intention was to investigate the claims of physiologist Ray Peat that the
essential fatty acids are not essential at all. I came away from my research believing that
they are, in fact, essential, but that mainstream textbooks and reviews made several
serious errors. One was that they grossly inflated the requirement. Another was that
they missed the most important point, that the requirement is far lower when supplied
by animal fats, especially liver.

My most stunning discovery was that the omega-3 fatty acid, EPA, might not even be a
normal constituent of the mammalian body. I stand by this discovery and it has shaped
my view of modern omega-3 research ever since.

That finding was overseen by Ralph Holman. When I was writing this report I called
him to discuss the implications of it, but he unfortunately was in his 90s and didn’t
remember the details of the experiments, conducted decades earlier.

I would now update my views from 2008 in several important ways:

In the report, I make arguments about how we should define “essential.” Today, I
would refine my language for greater clarity: something is physiologically essential if
it needs to be in the body to prevent signs and symptoms of deficiency. Something
is dietarily essential if it has to be present in the our food for the same reasons. In this
framework, the physiologically essential fatty acids are the omega-6 arachidonic acid

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 1/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

and the omega-3 DHA. These are conditionally dietarily essential depending on
nutritional status, genetics, and other factors that can help or hurt our ability to
synthesize them from the linoleic and alpha-linolenic acids found in plant oils. The
latter, however, are not essential in either sense, unless we stipulate that
arachidonic acid and DHA will not be present in the diet. That is, they become
essential conditional on the choice to consume an un-supplemented vegan diet.

In the report, I do refer to polyunsaturated fatty acids (PUFAs) as representing an

oxidative liability, but I also refer to them repeatedly as contributors to oxidative
stress. Today, I would refine my language by adopting the former exclusively and
dropping the latter. In other words, PUFAs do not cause oxidative stress. Rather, in
the presence of oxidative stress — caused by deficiencies of antioxidant nutrients,
illness, toxic exposures, or aging — they pose an oxidative liability. Their presence
in excess makes it more likely the oxidative stress will lead to a greater degree of
oxidative damage. Lesson 2 of my Antioxidant Course is the best place to learn
more about my framework for distinguishing between oxidative stress and
oxidative damage.

The distinction between causing oxidative stress and representing an oxidative

liability provides a framework for reconciling short-term benefits of PUFAs with
long-term harms. The best example of this is that PUFAs decrease the amount of
fat stored in the liver in the short-term, but in the long-term they worsen the
progression of simple fat accumulation to nonalcoholic steatohepatitis (NASH),
which is the pathway for the progression to fibrosis, cirrhosis, and liver failure. For
more on this, see my 2012 article, AJCN Publishes a New PUFA Study that Should
Make Us Long for the Old Days as well as Lesson 9 in my Antioxidant Course.

My analysis of the heart disease data in this report is honestly cherry-picked. I was
trying to illustrate some important points and had not yet had the chance to make
the comprehensive analysis of the data that I made later. My full analysis of the
topic on vegetable oils and heart disease is found in Lesson 13 of my Antioxidant
Course. The gist of this is that short-term well-controlled trials are neutral, but the
only trial lasting 8 years suggested that the initial benefit to heart disease is lost
with time as an aggravation of cancer risk emerges. That lesson does not cover fish
oils, but the situation is similar: trials lasting lasting less than one year showed the

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 2/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

bulk of the benefit and the only trial lasting more than four years found a 30%
relative increase in heart disease mortality.

I have since developed a much better-synthesized view of the interactions between

biotin, vitamin B6, riboflavin, and essential fatty acids in the usually candida-
infected skin lesions that are common to all of their deficiencies. This is found in
my recent article, High Protein? You Need More Biotin.

The report states that EPA can only be metabolized to compounds that resolve
inflammation in the presence of aspirin. There is now evidence that bacteria can
cause this conversion, so the ability of EPA to contribute to the resolution of
inflammation probably depends on the person according to their microbiome and
might interact with probiotics. I discuss and reference this on page 63 of my
COVID Guide.

The report states that one or two teaspoons of cod liver oil supplying one or two
grams of the sum of EPA and DHA has some support for use during pregnancy,
lactation, and childhood, but that otherwise these fatty acids should not be
specifically sought out, because a whole-foods diet with a mix of animal products
will provide everything needed. I would revise this in several ways:

First, I would not use one or two teaspoons of cod liver oil indefinitely, so this
should be limited to the context of pregnancy and lactation, where it was
originally studied. I would limit the childhood dose to 3/4 of a teaspoon, which
was the dose Weston Price used. My rationale for cod liver oil dosing is
explained in more detail in Nutrition and Immunity.

Second, some evidence has amassed to support one or two grams of the sum of
EPA and DHA for psychiatric disorders, with higher doses of EPA being
favored for depression, although the jury is still out on omega-3s and
psychiatric disorders in general. If EPA is more effective than DHA, this
suggests the effect is pharmacological rather than nutritional, and is a result of
the EPA acting as an NSAID and lowering peak inflammation. As I covered in
Nutrition and Immunity and in Good Fats, Bad Fats, this risks preventing the
full resolution of inflammation. Whether these high doses are needed to replete
levels of DHA in the nervous system in adulthood under some conditions needs
more research. I am open to the use of high-dose omega-3s in this context, but

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 3/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

I lean toward it being a pharmacological effect and I would not use it as a first
resort.

Third, even higher doses of EPA on the order of 4 grams a day has
pharmacologic benefit to reduce triglyceride levels. My suspicion is that this
effect results from the disruption of carbohydrate signaling, and is mainly
serving to disrupt the excessive synthesis of fat in people with underlying
insulin resistance. This might have greater value in people with genetic
hypertriglyceridemia, but if the problem is underlying insulin resistance I
believe that is best addressed directly with nutritional support and body
composition management.

My discussion of essential fatty acid deficiency in this report could be broadened to

include food intolerances and disruptions to all epithelial barriers, including the
gut and the blood-brain barrier. It could also be broadened to include how NSAID
use could be a widespread factor causing signs and symptoms of deficiency to arise
even when dietary supply of arachidonic acid is adequate. I cover this in Nutrition
and Immunity and in Good Fats, Bad Fats: Separating Fact From Fiction.

Finally, in the report I say that outside the context of pre-conception diets,
pregnancy, lactation, and early childhood, there is no particular reason to seek out
omega-3s on a whole foods diet. While I still largely agree with this, I think that,
besides the pharmacological uses covered above, consuming around one serving of
fatty fish per week alongside pasture-raised liver and egg yolks is a good thing, as it
would provide “reserve capacity” of omega-3s without going overboard.

Apart from those updates, I believe the information below remains as valuable as when I
wrote it in 2008. You can listen to the audio, or simply keep scrolling to read the entire
report in text format. Masterpass members can also download the PDF.

Listen to the Audio

The audio will be available soon on YouTube and in my main podcast feed.

Download the Report

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 4/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

Masterpass members can click here to go straight to the download page.

Everyone else can keep reading below.

Share This Report While Its Free!

This report is free for everyone today only. Please share it with everyone far and wide so
that those who would benefit can read it today while it’s free!

Make Sure You Have “Staying Immune

Through the Winter”
All subscribers to my Substack have free access to my 7-page quick guide to not getting
sick this winter. If you aren’t subscribed, subscribe below to get it immediately:

Subscribe here to get immediate free access to

“Staying Immune Through the Winter”

Type your email… Subscribe

If the box above says “upgrade to paid,” you are already a free subscriber and have the
guide sitting in your inbox. Search your mail for “Staying Immune Through the Winter”
and make sure everything going to Substack is headed to your primary inbox.

If it says “subscribed,” you are a Masterpass member and can download the guide here.

Abstract

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 5/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

Current reviews and textbooks call the omega-6 linoleic acid and the omega-3 alpha-
linolenic acid “essential fatty acids” (EFA) and cite the EFA requirement as one to four
percent of calories. Research suggests, however, that the omega-6 arachidonic acid (AA)
and the omega-3 docosahexaenoic acid (DHA) are the only fatty acids that are truly
essential. Eicosapentaenoic acid (EPA) occurs in fish products but is probably not a
normal constituent of the mammalian body, and in excess it interferes with essential AA
metabolism. The EFA requirement is inflated in the scientific literature by several
factors: the use of diets composed mostly of sucrose, glucose, or corn syrup; the use of
diets deficient in vitamin B6; the use of purified fatty acids instead of whole foods; the
use of questionable biochemical markers rather than verifiable symptoms as an index for
EFA deficiency; and the generalization from studies using young, growing animals to
adults.

The true requirement for EFA during growth and development is less than 0.5 percent of
calories when supplied by most animal fats and less than 0.12 percent of calories when
supplied by liver. On diets low in heated vegetable oils and sugar and rich in essential
minerals, biotin, and vitamin B6, the requirement is likely to be even lower than this.
Adults recovering from injury, suffering from degenerative diseases involving oxidative
stress, or seeking to build muscle mass mass may have a similar requirement. For
women who are seeking to conceive, or who are pregnant or lactating, the EFA
requirement may be as high as one percent of calories.

In other healthy adults, however, the requirement is infinitesimal if it exists at all. The
best sources of EFAs are liver, butter, and egg yolks, especially from animals raised on
pasture. During pregnancy, lactation, and childhood, one or two teaspoons of cod liver
oil may be useful to provide extra DHA, but otherwise this supplement should be used
only when needed to obtain fat-soluble vitamins. Vegetarians or others who eat a diet
low in animal fat should consider symptoms such as scaly skin, hair loss or infertility to
be signs of EFA deficiency and add B6 or animal fats to their diets. An excess of
linoleate from vegetable oil will interfere with the production of DHA while an excess of
EPA from fish oil will interfere with the production and utilization of AA. EFAs are
polyunsaturated fatty acids (PUFAs) that contribute to oxidative stress. Vitamin E and
other antioxidant nutrients cannot fully protect against oxidative stress induced by
dietary PUFAs. Therefore, the consumption of EFAs should be kept as close to the

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 6/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

minimum requirement as is practical while still maintaining an appetizing and

nutritious diet.

How Essential Are the Essential Fatty

Acids?
Beginning with the discovery in 1845 that pigs are capable of synthesizing fat from
carbohydrate through the 1920s, physiologists believed that neither fats nor their fatty
acid components were essential nutrients (1).

In 1920, Osborn and Mendel showed that rats consuming a diet only 0.3 percent fat by
weight but with added fat-soluble vitamins consumed much more food and grew more
vigorously than rats on a standard diet and concluded that “if true fats are essential for
nutrition during growth the minimum necessary must be exceedingly small” (2). These
researchers had been working with meat residue, purified starch, yeast and alfalfa. Over
the course of the next decade, however, investigators began using far more purified diets
composed of far more noxious ingredients and demonstrated the existence of what have
come to be known as the “essential fatty acids.”

The Discovery of the Essential Fatty Acids

In 1924, George Oswald Burr received his PhD in Biochemistry and Chemistry from the
University of Minnesota. After studying the effect of soil chemistry and climate on plant
sap in the Arizona desert for the summer, he moved to Berkeley to study the nature of
vitamin E with Herbert Evans, who had discovered the vitamin with Katherine Scott
Bishop just two years earlier. Since they were having trouble reproducing their vitamin
E-deficient diet, they developed an extremely simplified and purified diet based on
casein and sucrose. The new diets produced a more extreme deficiency that could not be
completely cured by vitamin E. Evans thought they had discovered a new vitamin, while
Burr suspected they had discovered the essentiality of certain fatty acids (3).

The next year, Burr married Mildred Lawson, the stock-keeper of Evans’ rats, and in
1928 they headed back to the University of Minnesota where Burr had been hired as the
head of plant physiology but told he could continue his work on nutrition (3). In 1929,

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 7/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

the Burrs published a landmark paper entitled “A New Deficiency Disease Produced by
the Rigid Exclusion of Fat from the Diet” (4) in the Journal of Biological Chemistry and a
subsequent paper the following year (5) in which they coined the term “essential fatty
acids” (EFAs).

The Burrs fed young, growing rats the highly purified diet developed in Evans’ lab with
yeast to supply B vitamins, a fat-free extract of cod liver oil to supply vitamins A and D,
and in some experiments a fat-free extract of wheat germ to supply vitamin E. The rats
developed irritated, sore, and scaly skin, dandruff, and hair loss. Their tails were
inflamed, swollen, scaled and ridged, and were hemorrhaging in certain spots. Their
kidneys degenerated and blood appeared in their urine. Females stopped ovulating and
became infertile. Rats of both sexes drank massive amounts of water that appeared to
simply evaporate since it produced no increase in urinary output. Despite eating much
more food, they gained much less weight; after several months they began to lose weight
and within six months to a year they all had died (4, 5).

To explain why their results differed so dramatically from those of Osborn and Mendel,
the Burrs argued that even highly purified corn starch still contains
0.6 percent of its weight as fat, and the meat residue and alfalfa likely contained non-
extractable fat that could not be detected. Thus, they argued, only a diet utilizing
sucrose and casein, which can be purified to a much greater extent than starch and meat
protein, could truly demonstrate the essentiality of the missing fatty acids (4).

None of the vitamins proved curative. Coconut oil, whether hydrogenated or non-
hydrogenated, produced no curative effect, and butter’s curative effect was very weak.
The fatty acid fraction of cod liver oil partially ameliorated the syndrome and prevented
the early death, while lard, liver, corn oil, flax oil, and olive oil proved fully curative (4, 5).
All of the fully curative oils had one thing in common: the presence of either linoleic
acid (linoleate) or arachidonic acid (arachidonate), both of which are omega-6
polyunsaturated fatty acids (PUFAs). Butter contains a small amount of both of these
fatty acids and would later prove fully curative when provided in larger amounts (6).
Subsequent experiments showed that purified linoleate and purified arachidonate were
each capable of fully reversing the deficiency syndrome when provided alone (7).
Arachidonate, however, proved to be at least three times more effective than linoleate;

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 8/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

since linoleate is a precursor to arachidonate, this effectively demonstrated that only

arachidonate is required to prevent or cure essential fatty acid deficiency.

The omega-3 fatty acids alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA)
were able to stimulate weight gain to some degree but had no power to cure dermatitis
(8), infertility, or many other symptoms (9). In fact, ALA made the dermatitis worse (10).
By 1950, a former graduate student of George Burr’s named Ralph Holman
demonstrated with his own graduate student C. Widmer that PUFAs were comprised of
two separate families of fatty acids: ALA was the precursor within the omega-3 family
and was converted in rat tissue primarily to DHA, while linoleate was the precursor
within the omega-6 family and was converted in rat tissue primarily to arachidonate (8).
These pathways are shown in Figure 1 1. Since omega-3 fatty acids could only
ameliorate some of the symptoms while omega-6 fatty acids were fully curative by
themselves, the omega-3 were largely ignored for decades to come. Later research,
however, would show that deficiencies of omega-3 fatty acids could be induced by the
addition of excess omega-6 to the EFA-deficient diet.

The deficiency diets used by the Burrs contained no meaningful amount of vitamin K,
which had not yet been discovered, but the isolated fatty acids proved curative even in
its absence. Thus it was clear that the observed EFA deficiency was a deficiency of
arachidonate.

The Mechanism of EFA Deficiency

To truly clinch the case that certain PUFAs are essential, advocates of the theory must
be able to explain the mechanism whereby they carry out their essential actions. The
best-supported mechanism is usually overlooked by both old and recent reviews: the
conversion of arachidonate to prostaglandin E2 (PGE2).

The dermatitis seen in EFA deficiency appears to result from an abnormal increase in
the permeability of the skin to water. The rats consume far more water than usual
without increasing their activity or their urinary output, and the skin condition only
manifests when the humidity of the laboratory is low. The water evaporates through the
skin, and the degree of water loss correlates with the severity of the dermatitis. When
deficient rats are placed in a covered beaker, they evaporate so much water that the
sides of the beaker fog up. The permeability defect appears to be non-specific: the skin

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 9/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

also becomes permeable to lethal chemicals to which it is normally impermeable, such

as barium sulfide (9). Topical PGE2 completely cures EFA-deficiency dermatitis (11),
probably because it stimulates the formation of gap junctions (12,13) and tight junctions
(14), which are protein-composed connections between cells that are responsible for
regulating the permeability of the skin barrier (15,16).

Rats with genetically defective gap junction formation develop scaly skin, increased
permeability of the skin barrier, defective ovulation, and infertility (15). Rats with
genetically defective tight junctions exhibit excessive water loss through the skin (16).
With either defect, most of the rats die relatively soon after birth. EFA-deficient rats
probably have much more mild deficiencies of the proteins involved in these junctions
and thus exhibit similar symptoms, though they survive longer.

The mechanism behind the failure to gain weight is much less clear. Whereas the
dermatitis and infertility are only cured by omega-6 fatty acids, the low bodyweight is
also cured, although less effectively, by omega-3 fatty acids (9). This suggests either that
the underlying mechanism of the cure is different or that there are two curative
mechanisms, one of which is specific to omega-6 fatty acids and the other of which is
general to all PUFA. There is some evidence that a hypersensitivity to thyroid hormone
could be responsible for the low bodyweight and death, but also considerable evidence
contradicting this hypothesis. The most compelling explanation is that EFA deficiency
causes a defect in the extraction of energy from food, causing an effective state of
starvation despite increased food intake. The precise mechanism of this defect, however,
is still uncertain. These possibilities are discussed in more detail in the sidebar, Are
EFA-Deficient Rats Hypersensitive to Thyroid Hormone?

It thus remains unclear whether the effect on bodyweight truly demonstrates the
essentiality of any specific fatty acids. Nevertheless, the fact that PGE2,
a product of arachidonate metabolism, completely resolves the dermatitis while fatty
acids that are not converted to arachidonate have no curative effect shows conclusively
that arachidonate plays an essential function in the body.

The EFA Requirement is Exceedingly Small

The simple fact that the Burrs could not demonstrate EFA deficiency in young rats
without a highly purified sucrose-casein diet suggested that the requirement

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 10/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

for these fatty acids during growth and development was extremely small. They
confirmed this by not only preventing the deficiency but fully curing it with whole foods
supplying EFA at well under one percent of calories. Sucrose-casein diets supplemented
with two percent lard by weight contained about 0.44 percent of calories as PUFA and
proved fully curative. The same diets supplemented with ten percent liver by weight
supplied about 0.12 percent of calories as PUFA and not only proved fully curative but
produced superior weight gain (4). Lard primarily contains the precursor fatty acid
linoleate and only traces of arachidonate, while liver contains nearly half of its PUFA as
arachidonate (35). Liver is also rich in vitamin B6, which enhances the conversion of
linoleate to arachidonate (10). Butter at ten percent of calories greatly reduced symptoms
and at forty percent of calories proved fully curative (6). Although amounts much less
than forty percent would probably also have proved fully curative, even this amount
provided only 0.56 percent of calories as linoleate and 0.08 percent as arachidonate.

The Burrs used purified linoleate to prove the point that the fatty acid itself was
curative, but used whole foods instead of purified fatty acids to estimate the EFA
requirement because of the damaging effect of the purification process. “All workers,”
they wrote, “recognize the fact that the acids isolated by the bromination method may
not have exactly the same structure that they had in the natural oil” (5). They cited
evidence that linoleate isolated by this method took on at least two different structures.
Indeed, studies using purified linoleate suggested that the requirement was just over
two percent of calories (7) – over four times the amount required when provided by lard
or butter. Purified arachidonate at 0.7 percent of calories also proved fully curative,
although the researchers did not test lower amounts (7). The existence of small amounts
of arachidonate in lard and butter is probably a major reason for their superiority, but it
is also possible that the linoleate from whole foods is much more effective than that
from purified preparations.

The EFA requirement is similarly low across species, as shown in Figure 2, EFA
Requirements Across Species Are Exceedingly Low. 2 Butter supplying 1.3 percent of
calories as PUFA prevented poor growth, scaly skin, and an increased susceptibility to
infections in human infants consuming a formula made partly from skim milk and
mostly from corn syrup (36), but the authors did not test lower amounts. The same
authors reported that both 1.3 and 2.0 percent of calories as purified linoleate

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 11/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

incorporated into a synthetic fat molecule cured eczema in infants on the same type of
formula (37). This requirement for purified linoleate is similar to that of the growing rat;
assuming that, like rats, humans respond better to animal fats than to purified linoleate,
it suggests that the EFA requirement for growing infants and children can be met by
animal fats providing 0.5 percent of calories as PUFA.

The EFA Requirement is Conditional

The EFA requirement is often presented in modern textbooks as one to two percent of
calories and recommendations for preventing EFA deficiency in adult humans are often
three percent of calories as linoleate; average intakes of PUFA in the United States
greatly exceed these amounts at six to seven percent of calories (17). Although the
estimates of the requirement are much lower than the average intake, they are greatly
exaggerated by several factors: the use of purified linoleate instead of animal fats
containing a mix of natural linoleate and arachidonate; the use of diets containing most
of their calories as sucrose, glucose, or corn syrup; the use of biochemical markers that
have never been shown to correspond to deficiency symptoms; the provision of
inadequate vitamin B6; and the generalization from studies conducted in young,
growing animals to the needs of adults. Even on highly purified diets composed mostly
of sugar, the requirement of young, growing animals for EFA from natural animal fats is
less than 0.5 percent of calories. The need would be much lower on diets low in sugar
and rich in vitamin B6; and in non-pregnant adults, the requirement is likely so low that
it would be impossible to acquire a deficiency no matter how strictly one tried avoiding
PUFA so long as one consumed a mix of natural foods of animal and plant origin. In
fact, evidence suggests that the requirement for EFA per se is strictly conditional upon
growth.

See sidebar, Is Linoleate Essential to Skin Health? 3

The only attempt to induce EFA deficiency in an adult human ever performed was in
1938 when the biochemist William Brown volunteered to go six months on an EFA-
deficient diet in George Burr’s laboratory (43). Each day, he consumed three quarts of
defatted milk, a quart of cottage cheese made from it, sucrose, potato starch, orange
juice, and some vitamin and mineral supplements. The decrease in his blood levels of
arachidonate and linoleate was similar to that seen in cases of infant eczema associated

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 12/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

with EFA deficiency, but rather than experiencing adverse effects, he experienced a
marked absence of fatigue, a normalization of his high blood pressure, and the complete
disappearance of the migraines he had suffered from since childhood.

Dermatitis seemingly associated with EFA deficiency has been associated in adult
humans with total parenteral nutrition (TPN), which is an intravenous infusion of a
liquid diet. These diets, however, were also deficient in vitamin K, iron, zinc, and
various other trace elements. In one case the dermatitis failed to resolve with topical
application of corn oil (52), and in other cases resolved upon combined supplementation
with EFA and zinc (44); the lack of clear evidence that the dermatitis can resolve upon
EFA treatment alone makes the case for EFA deficiency weaker. Moreover, all of the
subjects receiving TPN had severe underlying health problems, were often undergoing
major gastrointestinal surgery, and were sometimes at the brink of death. Further, TPN
by nature provides a continuous infusion of glucose, which prevents the breakdown of
adipose tissue that would ordinarily occur between meals and thus prevents the freeing
of stored linoleate for conversion to arachidonate (45).

Researchers at the University of Wisconsin Madison made the first attempt to produce
EFA deficiency in adult rats in 1947 (46). The only way they were able to induce a
deficiency was by starving the rats until they lost half of their bodyweight, and then
allowing them to feed freely for two months as they gained back the weight they had
lost. Typical symptoms of EFA deficiency such as scaly skin and hair loss set in during
the period of recovery and were prevented or cured by a small amount of corn oil. Even
in the non-supplemented rats, however, the symptoms spontaneously disappeared in the
third month of the study.

While the EFA requirement in adulthood appears to be greatly reduced compared to

that during growth and development, the requirement during pregnancy appears to be
increased. An experiment conducted in the 1940s demonstrated that EFA deficiency
leading up to and continuing through pregnancy led to extended labor over two to three
days with excessive hemorrhaging, the death of some mothers after birth, and within
two days the death of all of the young. The investigators used purified fatty acids and
concluded that the requirement to support a healthy pregnancy was about double the
requirement to prevent or cure dermatitis in young, growing rats (47). This suggests that

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 13/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

the EFA requirement during and preceding pregnancy is about one percent of calories
when supplied by lard or butter and one quarter this amount when supplied by liver.

See sidebar, Changes to the Endocrine System in EFA Deficiency 4

See side bar. Are EFA-Deficient Rats Hypersensitive to Thyroid Hormone? 5

We can conclude, therefore, that the requirement for EFA is conditional upon growth,
including fetal growth during pregnancy, and might also be conditional in cases of
continuous parenteral infusion of glucose. “Growth” probably includes recovery from
any injury, since this involves the synthesis of new tissue and the prostaglandin-
dependent formation of junctions between cells, and muscle-building, since the
expansion of existing cells would require new membrane fatty acids. Additionally,
alcoholism, diabetes, insulin resistance and certain genes decrease the activity of delta-
six desaturase, one of the enzymes involved in the synthesis of arachidonate from
linoleate (48). It seems probable that the combination of one of these conditions or genes
with a strictly vegetarian diet excluding all forms of animal fat could lead to a deficiency
of arachidonate. If an EFA requirement for most healthy adults on a mixed diet exists at
all, however, it must be so low that it is essentially impossible to achieve a deficiency.
During periods of growth or recovery from injury, animal fats providing 0.5 percent of
calories as EFA are probably sufficient; and during pregnancy, animal fats providing one
percent of calories as EFA are probably sufficient. On diets low in sugar and rich in
vitamin B6, especially diets including liver, the requirement is almost certainly even
lower than this.

The EFA Requirement is Affected by Other Nutrients

A number of energy molecules, vitamins, and minerals affect the requirement for EFA.
The overall effect of these interactions is probably to reduce the requirement for EFA
during growth and development on a whole foods diet inclusive of animal fats to much
lower than the 0.5 percent of calories suggested by most animal experiments.

Cholesterol at one percent of the weight of the diet, which is like a human eating 75
eggs per day, aggravated the dermatitis in EFA deficiency but had no effect on the
amount of linoleate required to cure it. It aggravated testicular degeneration in the
absence of EFA, but enhanced testicular development when EFA was provided (56). Pure

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 14/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

saturated fat from fully hydrogenated coconut oil (HCO) had no effect on dermatitis in
rats regardless of EFA status (57), but in human infants fed EFA-deficient diets with 85
percent of calories as corn syrup, replacing half of the corn syrup with HCO improved
the skin condition (36). In rats, HCO had no effect on weight gain in the absence of EFA,
but in the presence of sufficient linoleate, it enhanced weight gain (57). HCO greatly
increased the PUFA content of tissues in these rats, probably by protecting them against
the free radicals that destroy hem (see sidebar, EFA Deficiency, Free Radicals, and
High-Sugar Diets 6). Thus, on a diet of mixed whole foods of animal and plant origin,
the inclusion of foods rich in saturated fat and cholesterol should enhance EFA status.
Indeed, foods such as butter, lard, liver, and presumably egg yolks, are the most effective
sources of EFA because they contain preformed arachidonate.

Dietary protein might accelerate kidney damage in EFA deficiency, but has no effect on
the amount of EFA required to prevent the damage (4). Refined sugars such as sucrose,
glucose, and corn syrup increase the need for EFA to such a degree that it has been
almost impossible to demonstrate EFA deficiency without them. Magnesium deficiency
aggravates EFA deficiency in pigs, perhaps by acting synergistically with excess glucose
to increase oxidative stress (see sidebar, EFA Deficiency, Free Radicals, and High-Sugar
Diets).

Two B vitamins are essential for the conversion of linoleate to arachidonate: biotin and
vitamin B6. The conversion consists of multiple elongations of the hydrocarbon chain
and introductions of double bonds between its carbon atoms, a process called
desaturation (see Figure 1). Biotin is necessary for the elongation steps (58) and vitamin
B6 is necessary for certain desaturation steps (10). The same enzymes and cofactors are
used for the conversions of the omega-3 fatty acid ALA to EPA and of EPA to DHA.
Biotin-dependent elongation is necessary for the synthesis of all fatty acids while
vitamin B6-dependent desaturation is only necessary for PUFA metabolism, so the
relationship of vitamin B6 to EFA deficiency is much more specific. The administration
of vitamin B6 to EFA-deficient rats causes a dramatic increase in the synthesis of
arachidonate from linoleate and resolution of the deficiency symptoms (10).

Calcium deficiency (59) and the consumption of rancid vegetable oil (60) both indirectly
but substantially impair desaturation. Dietary protein and total energy intake increase
the conversion of linoleate to arachidonate. Zinc deficiency seems to impair this

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 15/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

conversion; the effect, however, seems to be mostly (61) though perhaps not entirely (62)
due to reduced food intake.

Thus a diet rich in essential minerals, biotin, B6, and low in refined sugars would
provide a context in which the EFA requirement during growth and development would
probably be much lower than the 0.5 percent of calories observed for most animal fats
and 0.12 percent of calories observed for liver, and if a requirement during adulthood
exists at all it would be even lower. Likewise, the requirement during pregnancy would
probably be much lower than the one percent of calories for most animal fats and one-
quarter percent of calories for liver inferred from animal experiments. Indeed, these
original figures may have been inflated in the first place because the experiments did
not test lower amounts. Clearly, the requirements are so low that on a nutritious, whole
foods diet inclusive of animal fats it would be impossible to reduce one’s PUFA intake to
the minimum requirement. The question for those of us who do not consume
industrially purified sucrose-casein diets, then, as we will see in subsequent sections, is
not so much how much PUFA to obtain, but how strictly we should avoid an excess of
PUFA.

There are two exceptions to this rule: strict vegetarianism and high intakes of omega-3
fatty acids. The EFA requirement might be higher on a vegetarian diet in which the EFA
is supplied by plant oils that do not contain any arachidonate, but the inclusion
of bananas in such a diet, which are very rich in bioavailable B6, would probably help
keep it low. Strict vegetarians who develop skin problems, hair loss, or infertility should
first try adding vitamin B6 to their diet if they have ethical objections to animal foods; if
this fails, they should add animal fats. As we will see in the next section, omega-3 fatty
acids become essential when linoleate is supplied in the diet at several percent of
calories. Under many conditions, however, consumption of omega-3 fatty acids may lead
to the accumulation of EPA, a fatty acid that both suppresses the production of
arachidonate and interferes with its utilization. An excess of omega-3 fatty acids, then,
could also lead to a deficiency of arachidonate, in which case the proper solution is to
correct the excess of omega-3 rather than trying to get more omega-6.

The Essentiality of Omega-3 Fatty Acids

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 16/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

The fact that purified EFA-deficient diets in animals and fat-free intravenous feedings
in humans produced no symptoms specifically curable by omega-3 fatty acids led the
research community to ignore them for decades. Once Ralph Holman and his colleagues
convinced the medical establishment to begin including linoleate in the intravenous
infusions to prevent omega-6 deficiency, however, suddenly a new deficiency was born.

In 1982, Holman reported the first case of apparent omega-3 deficiency in a six-year-old
girl who underwent repeated rounds of surgery for an abdominal gunshot wound and
was maintained for over five months on total parenteral nutrition (TPN), an intravenous
infusion of a liquid diet. The FDA had recently approved the addition of vegetable oils
to TPN to provide EFA, and two formulas were then available: one containing safflower
oil and one containing soybean oil (63). The safflower oil formula contained an omega-6-
to-omega-3 ratio of 115, while the soybean oil formula contained a ratio of six, almost
twenty times lower (64). After five months on the safflower oil formula, the girl
experienced episodes of numbness, tingling, weakness, inability to walk, leg pain,
psychological disturbances, and blurred vision – symptoms that had never been seen in
EFA-deficient animals or humans receiving fat-free TPN.

Her blood levels of omega-3 fatty acids were low. When her physicians switched her to
the soybean oil formula, her omega-3 fatty acid levels returned to normal and her
neurological symptoms disappeared.

Animal experiments and tissue analyses suggest that the omega-3 fatty acid DHA is the
essential product of the omega-3 family just as arachidonate is the essential product of
the omega-6 family (see sidebar, Is EPA an Essential Fatty Acid?). DHA is especially
enriched in the brain and retina, where its concentration is tightly regulated: during a
critical window in the early development of these tissues, small amounts of omega-3
fatty acids are required to provide maximal DHA content; after this window, the brain
and retina are very resistant to the effects of deficiency. The synthesis of DHA from
ALA requires all the same enzymes and cofactors required for the synthesis of
arachidonate from linoleate; thus, if preformed DHA is not supplied in the diet, an
excess of linoleate will compete with ALA for these enzymes and suppress the formation
of DHA. At all time points, therefore, maximal depletion of DHA requires an excess of
omega-6 fatty acids in the diet.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 17/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

When fed to weanling rats for the first eleven months of life, EFA-deficient sucrose-
casein diets deplete retinal DHA concentrations by only 15 percent compared to normal
laboratory diets. The addition of just over ten percent of calories as safflower oil,
however, causes a much more dramatic 50 percent depletion (65). Feeding rats for a
similar amount of time just over two percent of their calories as purified linoleate with
no other source of fat produces even more dramatic results: 62 percent depletion occurs
in the first generation; if the females are bred with normal males and their second-
generation pups are fed on the same diet, 92 percent depletion occurs (66). Similar
results occur in the brain of the weanling rat: if linoleate is kept under two-thirds of a
percent of calories, restricting omega-3 intake to as little as 0.05 percent of calories has
essentially no effect on DHA levels regardless of the omega-6-to-omega-3 ratio (67); two
generations of feeding two percent of calories as purified linoleate with no other source
of fat, however, depletes DHA levels by over 90 percent (68). These results suggest that
the requirement of young rat pups for omega-3 fatty acids is incredibly small, and that
the nutritional status of the mother and the excess omega-6 content of the diet are much
more important determinants of brain and retinal DHA concentration than the omega-3
content of the diet.

Nervous tissue maintains very tight control of the chain length and unsaturation of its
fatty acids. It is especially enriched in arachidonate, which has 20 carbons and four
double bonds, and DHA, which has 22 carbons and six double bonds. These two fatty
acids preferentially cross the placenta and rapidly accumulate in the brain in the third
trimester of pregnancy and are also supplied in breast milk. When the DHA content of
the nervous tissue declines in the depletion studies, the tissue synthesizes a rare omega-
6 fatty acid with 22 carbons and five double bonds called docosapentaenoic acid (DPA)
to replace it. Even on an EFA-deficient diet devoid of omega-6 fatty acids – which can
only be given to the weanling rats because mothers become infertile on such a diet – the
nervous tissue will convert its arachidonate into DPA in order to replace the DHA.
Simultaneously, it will convert the oleate it synthesizes from carbohydrate into the 20-
carbon, 3-double bond Mead acid to replace the arachidonate (65). When omega-6 fatty
acids are in abundant supply, however, the synthesis of Mead acid is suppressed and the
arachidonate level remains normal, but the otherwise absent DPA still replaces the DHA
(67). Since this tightly regulated system of fatty acid synthesis within the nervous tissue
would invariably produce high levels of arachidonate and DHA on anything resembling

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 18/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

a normal diet even when PUFA intake is very low, it very strongly suggests that these
fatty acids are essential to the functioning of the nervous system.

The DPA that accumulates in the brain during DHA depletion cannot fulfill the
functional role of DHA. Experiments with rats have shown that DHA depletion using
high omega-6 diets definitely leads to visual deficits and possibly to learning deficits –
although since most learning tasks involve vision it has been difficult to differentiate the
two (79). The visual system of the human is much closer to the visual systems of other
primates than it is to that of rats. Several experiments in rhesus monkeys have shown
clear visual deficits with DHA depletion (69, 70). These experiments fed adult females a
sucrose-casein diet using either safflower oil or soybean oil for at least two months
before conception and throughout pregnancy and then removed the infants five days
early by caesarian section and fed them an artificial formula for twelve weeks containing
30 percent of its calories as whichever type of fat the infant’s mother had received. They
measured their visual acuity by showing them black-and-white stripes
of varying widths against gray backgrounds; since this type of patterned stimuli
inherently draws the attention of infant monkeys, whether they look at the card
demonstrates whether they see the stripe. The safflower oil had an omega-6-to-omega-3
ratio of 255, while the soybean oil had a ratio of seven. In the monkeys receiving the
safflower oil diet, DPA replaced the DHA in their brain and retinal tissue, and visual
acuity was substantially impaired.

Evidence suggests that human infants benefit from preformed DHA. During pregnancy,
the fetus incorporates DHA into its brain at ten times the rate at which it can synthesize
it, probably by hoarding preformed DHA from the mother and selectively transporting
that DHA into the nervous system (71). Even though the concentration of DHA in breast
milk is very small, the brains of breast-fed infants accumulate fifty percent more DHA
than those of infants fed formulas devoid of the fatty acid (72). Most importantly, in a
double-blind, placebo-controlled trial, the maternal use of two teaspoons of cod liver oil
per day during pregnancy and lactation caused a significant increase in the mental
processing score of the children at four years of age. The cod liver oil provided just over
one gram of DHA but the two diets were adjusted to provide equal amounts of fat-
soluble vitamins. Unfortunately the placebo was corn oil and led to a 48 percent higher
intake of linoleate; nevertheless, the DHA intake was seven-fold higher in the cod liver

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 19/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

oil group than in the corn oil group and the only dietary variable associated with IQ in
the final analysis was the total maternal intake of DHA (73).

See sidebar, Inflating the EFA Requirement with the Triene-to-Tetraene Ratio 7

The requirement of the healthy, non-pregnant adult for DHA is probably minimal,
especially if the intake of omega-6 PUFA is kept low. In the developing chick, large
doses of fish oil are only capable of influencing brain levels of DHA within the first two
to three weeks after birth (74). In rats, an EFA-deficient sucrose-casein diet primarily
depletes DHA levels in the retina during the first three months; thereafter, the tissue
seems to play “catch up” for a few months and recuperate a small amount of its DHA
with no further depletion taking place through eleven months, which is middle age for
the rat (65). No natural diet could possibly restrict omega-3 fatty acids to anywhere near
the level of a purified sucrose-casein diet, and small amounts of preformed DHA are
found in all animal products. Virtually any mixed diet that excludes excess omega-6 fatty
acids, then, should provide sufficient DHA for the healthy adult. If one has any doubts,
however, the use of pasture-fed butter and eggs and the occasional use of cod liver oil or
fatty fish should provide well more than enough.

The adult requirement for DHA is probably conditional not only upon pregnancy but
also upon disease states that cause the oxidative destruction of DHA in tissues. Virtually
all neurological diseases are associated with decreased levels of PUFA in humans,
especially of omega-3 fatty acids but also of omega-6; a number of other liver, kidney,
intestinal and immune diseases also show reductions in PUFA levels (52). This is
probably because the oxidative stress associated with these diseases leads to the
destruction of the PUFA. A study using mice spliced with a human Alzheimer’s-related
gene suggested that the loss of DHA in this disease contributes to the overall pathology.
Dietary depletion of omega-3 fatty acids had no effect on brain DHA or learning
capacity in normal mice, but in the gene-spliced mice it caused major depletion of brain
DHA, oxidative destruction of important neural proteins, and an impaired ability to
navigate through a water maze. Adding DHA to the diet not only restored the DHA
levels of the brain but eliminated the oxidative destruction of neural proteins and
restored the normal cognitive capacity of the rats (75). DHA can be oxidized to a
signaling compound that directs the cell to turn on its antioxidant defense genes (76);

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 20/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

when it is lost, the antioxidant defenses would therefore fail. DHA thus seems to stand
in the breach between pro-oxidants and the oxidative destruction of nervous tissue.

The results of these studies clearly demonstrate that the requirement for omega-3 and
omega-6 fatty acids is primarily restricted to developing infants and children and
pregnant and lactating women, that the requirement for omega-6 fatty acids on a
healthy diet is incredibly small so long as they are supplied by animal fats containing
preformed arachidonate, and that the requirement for omega-3 fatty acids is even
smaller so long as excess omega-6 fatty acids are avoided. During recovery from illness
or degenerative disease associated with oxidative stress, increasing arachidonate and
DHA intake from foods such as liver, egg yolk, and moderate amounts of cod liver oil
may be useful. As we will see below, however, minimizing the total intake of PUFA is an
important part of avoiding the oxidative stress to begin with.

The Perils of Excess PUFA

In 1985, the lipid researcher Hugh Sinclair gave a pre-banquet speech on his 75th
birthday before the Second International Congress on Essential Fatty Acids,
Prostaglandins and Leukotrienes in London in which he described the deleterious
effects of 100 days on an “Eskimo diet” of seal blubber and undeodorized mackerel oil
(81). He went on the diet to measure his bleeding time because the weather during a
recent trip with several colleagues to northwestern Greenland had curtailed them from
measuring the bleeding times of real Eskimos. Despite a daily supplement of vitamin E,
his blood and urine levels of malondiadehyde (MDA) – a product of the oxidative
destruction of PUFA – rose to fifty times the normal level. Although MDA causes birth
defects, Sinclair was not worried about having “misshapen offspring” because his sperm
count dropped to zero.

Sinclair’s experience represents two of the most important perils of consuming excess
PUFA: a great excess of one family can interfere with the function of the other, and an
excess of any type of PUFA raises the level of oxidative stress within the body. Sinclair
would doubtlessly have replicated the Eskimo diet better under the guidance of an
Eskimo. Physiologist Ray Peat has suggested that the consumption of endocrine glands
and other organ meats on the actual Eskimo diet may have protected them against some
of the harmful effects of excess PUFA by increasing their metabolic rate (82). These

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 21/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

tissues are also rich in arachidonate, which is required for the production of sperm (see
sidebar, Changes to the Endocrine System in EFA Deficiency). Although oxidative
stress contributes to sperm damage (83), the excess EPA from the fish oils may thus also
have interfered with the arachidonate-dependent production of sperm.

The Omega-6-to-Omega-3 Ratio

As discussed in the main text in the The Essentiality of Omega-3 Fatty Acids section
and the sidebar, Is EPA an Essential Fatty Acid?, 8 an excess of the omega-6 linoleate
will interfere with the synthesis of elongated omega-3 fatty acids from ALA in general
and will tend to increase EPA levels at the expense of DHA. The other critical
interaction between these two families is the ability of EPA to interfere with
arachidonate metabolism. Although EPA is generally not found in significant amounts
in tissues of animals fed on ALA- containing diets, fish oils will provide large amounts
of it and lead to its accumulation. Unlike DHA, EPA does not have its own place in cell
membranes. Because it is a 20-carbon PUFA just like arachidonate, it is very similar in
structure and competes with all of the enzymes that metabolize arachidonate, including
those that place it in cell membranes and those that free it from these membranes and
synthesize prostaglandins from it (17). The prostaglandins made from EPA do not fulfill
the functions of those made from arachidonate; thus, EPA aggravates EFA-deficiency
dermatitis (10) and probably aggravates the decline in sperm production seen in EFA
deficiency. Maternal and infant blood levels of arachidonate are also correlated with
infant growth before and after birth and there is some limited evidence that the addition
of EPA to formula for premature infants decreases growth but that the addition of DHA
does not (84).

Out of ten populations from five different continents, American adults have the highest
omega-6 levels and American infants have the lowest omega-3 levels
(63). An oft-cited study on the omega-6-to-omega-3 ratio showed that the optimal ratio
in rats for learning and the resistance to pain and hypothermia is four (85). This study
used purified linoleate and ALA. The ratio is likely to be much less important under two
conditions: when the total intake of PUFA is low and when animal fats provide
preformed arachidonate and DHA.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 22/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

As shown in Figure 1, all of the same enzymes and cofactors are used to convert
linoleate to arachidonate, ALA to EPA, and EPA to DHA. Linoleate from vegetable oil,
ALA from flax oil, and EPA from fish oil will not only compete with
each other for these enzymes but an excess of any of them will decrease the production
of those enzymes, aggravating the effect of the competition. When the total intake of
PUFA is low, the production of the enzymes is high, and the competition is less
important. This is probably why when rats are fed less than
one percent of calories as total PUFA during their first months of life, the ratio can vary
between 0.04 and 12.1 without any meaningful effect on the DHA content of their brains
(67). Moreover, while EPA competes with arachidonate for positions in the cell
membrane, DHA has its own place in the membrane and does not directly compete with
other fatty acids. When DHA and arachidonate are supplied directly in the diet, there is
little if any competition between the two; if the total intake of PUFA is low, small
amounts of EPA in the diet are more likely to be converted to DHA. Under these
conditions, while diet will expectedly have some influence on membrane composition,
the membranes will most likely largely regulate themselves.

PUFAs Promote Oxidative Stress

The mammalian body seems to do everything in its power to get rid of excess PUFA.
The 18-carbon fatty acids linoleate and ALA are essential to plants and accumulate in
their membranes, where they protect them from cold spells and are enzymatically
converted into hormones. Studies in rats, humans and other primates show that these
fatty acids are burned for energy at a far greater rate than monounsaturated and
saturated fatty acids or the elongated PUFA. In rats, about 60 percent of them are
burned for energy, 20 to 30 percent are broken down into their basic building blocks for
the synthesis of saturated and monounsaturated fats and cholesterol, and apart from the
small amount used to synthesize the elongated products, most of the rest are secreted
into the fur (18). Not even extreme EFA deficiency (86) or the provision of abundant
saturated and monounsaturated fats on a high-fat, ketogenic diet (87) stops the
conversion of 18-carbon PUFA to more saturated lipids. Nevertheless, a substantial
portion of dietary PUFA still accumulate over time in cell membranes (88).

Perhaps the reason the mammalian body appears to be hard-wired to get rid of the bulk
of these fatty acids is because their excessive inclusion in cell membranes presents an

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 23/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

oxidative liability that can wreak havoc on the cell. PUFAs are fatty acids that contain
two or more double bonds between carbon atoms. Double bonds make a fatty acid very
easily oxidized – that is, they make its electrons easily stolen by free radicals. Because
the typical oxidation reaction that occurs in cell membranes requires the presence of
two double bonds positioned near to one another, it is primarily PUFA rather than
monounsaturated fatty acids that are vulnerable to oxidation (see Figure 3, PUFAs Are
Easily Oxidized 9). The more double bonds they have, the more susceptible they are.
Oxygen binds to PUFA at the site of the oxidized double bond, turning the fatty acid
into a peroxyl radical. Peroxyl radicals initiate chain reactions within cellular
membranes by interacting with other PUFA; in each reaction, the peroxyl radical
becomes a lipid peroxide and the second PUFA becomes a peroxyl radical that can go on
to react with a new PUFA; the cycle continues, repeating this process. In the presence of
certain metals, the lipid peroxides will break down completely into products such as
MDA (see Figure 3, PUFAs Are Easily Oxidized), which can infiltrate the rest of the cell
to damage proteins and DNA. Lipid peroxides themselves can be enzymatically cleaved
from the membrane and cause damage to the rest of the cell.

The consumption of fresh, unoxidized DHA, EPA or omega-3-rich perilla oil increases
markers of oxidative stress in rats (89). Rats fed 30 percent of their diet as corn oil have
double the lipid peroxidation, half the aerobic capacity, and 42 percent lower glycogen
stores in their heart tissue compared to rats fed an equal amount of coconut oil (90).
Evidence suggests that this increase in oxidative stress increases the risk of cancer,
heart disease, aging, and virtually all degenerative diseases.

Many studies have shown that dietary PUFA increases the risk of chemically induced
cancer. For example, a carcinogen called DMBA induced tumors in 40 percent of rats
eating a diet with two percent total fat, 78 percent of rats eating a diet with two percent
linoleate and 18 percent coconut oil; and 100 percent of rats fed twenty percent corn oil.
Other vegetable oils produce similar results. Fish oils also increase
the incidence of cancer in these models, but are less dangerous than corn oil (88).
Perhaps the fish oil is less dangerous because the DHA can be oxidized into
a signaling molecule that stimulates the cell to turn on its antioxidant defenses,
although this is only verified in neural tissue (76).

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 24/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

In the 1950s, researchers showed that the replacement of saturated fats with PUFA in
tightly controlled and formulated “milk shakes” could reduce cholesterol levels (91). In
the following years, the Federal government and the American Heart Association
endorsed the hypothesis that cholesterol concentrations in the blood were the driving
force behind heart disease and mainstream medicine began promoting the consumption
of PUFA to protect against it. The modern understanding of the role of lipids in this
disease, however, has changed dramatically. The most recent edition of the respected
textbook, Modern Nutrition in Health and Disease, suggests that it is PUFA, not saturated
fats, that contribute to heart disease:

Theories regarding the genesis of atherosclerotic lesions have paralleled

the development of the field. It is accepted currently that atherosclerosis has its
origins in inflammation. Atherosclerosis is characterized by aortic accumulation
of lipids as well as other chemical entities. Oxidation products of LDL are readily
taken up by macrophages to form the foam cells that characterize the atherosclerotic
plaque. Oxidized LDL, rather than LDL per se, is now regarded as a prime inducer of
the atherosclerotic process (92).

Elsewhere the same textbook states:

Nutritional and biochemical studies suggest that diet can modulate the susceptibility
of plasma LDLs to oxidative degradation by altering the concentration of PUFAs and
antioxidants in the lipoprotein particle. The first target of peroxidation in the
oxidation of LDLs consists of PUFAs of [phospholipids] on the LDL surface (17).

Oxidized LDL inhibits the production of nitric oxide (93), which is one of the body’s
most potent weapons against heart disease: it dilates blood vessels, decreases the
adhesion of white blood cells to the lining of the vessel walls, inhibits the migration of
smooth muscle cells to the sites of atherosclerotic lesions, and decreases the formation
of blood clots. Oxidized LDL also transforms white blood cells into the “foam cells” that
accumulate lipids and clog up the vessel wall by causing the white blood cells to flip on
the relevant genes (94). Once the oxidation of PUFA in the LDL particle begins,
oxidative damage spreads to the protein that weaves itself through the membrane and
then to the cholesterol at the core; but the specific components of the oxidized LDL
particle that turn on the foam cell genes are oxidized derivatives

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 25/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

of linoleate (95). Substitution of polyunsaturated linoleate for monounsaturated oleate or

the addition of several grams of fish oil, even compared to a corn oil placebo, increases
the susceptibility of LDL particles to oxidation (96).

It should therefore be unsurprising that the Harvard School of Public Health in

conjunction with Tufts University and several other institutions published a prospective
study in 2004 in the American Journal of Clinical Nutrition showing that the progression of
atherosclerosis in postmenopausal women was directly correlated with PUFA intake
and inverse correlated with the intake of saturated fat. For every five percent of calories
consumed as saturated fat, the women had a 0.16 millimeter lower increase in the
narrowing of the arteries, and those with the highest intake of saturated fat actually had
a reduction in atherosclerosis over time. For every five percent of calories consumed as
PUFA, there was a 0.17 millimeter greater increase in narrowing. Carbohydrate intake
was also associated with narrowing but to a lesser extent (97).

The editors of the journal called the study the “American Paradox” (98). They contrasted
it to the findings of the Finnish Mental Hospitals Study, which they called “one of the
earliest and most convincing studies of the better efficacy of unsaturated than of
saturated fat in reducing cholesterol and heart disease.” This study, however, was
seriously flawed. It fed mental hospital patients two identical diets for six years, but one
group received margarine instead of butter as well as milk whose fat had been replaced
with soybean oil; then the two groups were switched for another six years. The main
flaw in the design was that the subjects came and went: if they left the hospital for years
and came back, they were included in the final analysis; even if they began their stay at
the hospital a month before the 12-year study ended, they were also included; but if they
left at any time point without returning, they were excluded. This type of design opens
up the study not only to accidental confounding but also to the potential for malicious
manipulation. The American paradox, then, isn’t really a paradox at all.

Studies testing the effect of omega-3 fatty acid supplements such as fish oil on heart
disease risk are conflicting but do not support a preventative role for fish oil in healthy
adults. A recent Italian trial found that a combined EPA and DHA supplement
providing just under a gram of omega-3 fatty acids per day to patients who had
experienced a heart attack within the previous three months reduced cardiac and
sudden death, but only in patients with arrhythmia or who were taking beta-blockers,

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 26/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

and no effect was seen on non-fatal heart attacks (99). Consistent with this, the first Diet
and Reinfarction Trial (DART) found a decreased risk of all-cause mortality among heart
attack survivors advised to eat fatty fish or take fish oil, while the second DART trial
found an increased risk of cardiac and sudden death among patients who only had stable
angina and who supplemented with fish oil; the increase in risk was only found in
patients who were not taking beta-blockers or calcium-channel blockers (100). These
studies suggest that the benefit of fish oil supplementation is restricted to a specific
subset of patients with established heart disease and may be harmful to those outside
this select group. A recent meta-analysis that pooled the results of 14 prospective trials
concluded that omega-3 fatty acids reduced the risk of heart disease more effectively
than statins and other lipid-lowering drugs (101). But the only primary prevention study
the authors included – that is, the only study aimed at preventing heart disease in those
who did not already have it – found a six-fold increase in total mortality, although the
study was not statistically powerful enough to conclusively distinguish the effect from
that of chance. The results of these trials clearly cannot be taken to suggest that fish oils
will prevent heart disease in healthy individuals.

Since most other degenerative diseases also seem to have an important component
involving oxidative stress, the intake of excess PUFA is probably related to virtually all
of them, especially those associated with aging. For example, animal studies have shown
that the substitution of saturated tallow for polyunsaturated corn oil dose-dependently
protects against alcoholic fatty liver disease (102), that both omega-3 and omega-6 PUFA
increase the ability of the chemical alloxan to induce diabetes while saturated fats are
protective (103), and that substitution of polyunsaturated sunflower oil for
monounsaturated olive oil dramatically increases the age-associated accumulation of
DNA damage (104).

Can Antioxidants Protect Against the Perils of PUFA?

Vitamin E is an important antioxidant in cell membranes, but it cannot cure damage
that has already been done. Inevitably, at least small numbers of free radicals produced
in the normal metabolism of the cell will escape into the membrane and oxidize lipids.
Vitamin E can prevent the initial damage from causing a chain-reaction by converting
peroxyl radicals to lipid peroxides, but these compounds can be enzymatically cleaved
from the membrane and wreak havoc on the cell. Gluathione is required to convert the

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 27/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

lipid peroxides into hydroxy-fatty acids. These compounds are immune to further
oxidation and thus unlikely to cause direct damage to other cellular constituents (105),
but they are also the main components of oxidized
LDL particles that stimulate the transformation of white blood cells into foam cells,
conferring on them the ability to accumulate lipids and stick to the insides of the blood
vessel wall (95). The accumulation of hydroxy-fatty acids could also have adverse effects
on the structural properties of cell membranes.

Although vitamin E is essential to the protection of cellular membranes, most of it is

stored in adipose tissue. A portion of dietary PUFA is also stored in adipose tissue, and
apparently draws in extra vitamin E from the blood, lowering blood levels of vitamin E
and delivery of vitamin E to cell membranes. Because the turnover of vitamin E is faster
than the turnover of PUFA, vitamin E requirements may remain elevated for up to four
years after discontinuing a high-PUFA diet (106).

Vitamin E has been shown to ameliorate some of the deleterious effects of PUFA, but its
protection is partial at best. A number of studies have shown that it protects against
cancer (88), but it offers no protection against diabetes or mortality induced by the
combination of PUFA and alloxan (103). A placebo-controlled trial published in 1997
showed that fish oil supplying just over six grams per day of omega-3 fatty acids
administered to healthy men for six weeks raised lipid peroxides by 20-35 percent and
MDA levels by 60-70 percent; 900 IU of vitamin E per day – which is about 15 times the
RDA and far more than one could possibly get from food – had no protective effect at all;
in fact, the deleterious effects were even worse in the vitamin E group, though the
difference could have been due to chance (107).

Coenzyme Q10 (CoQ10) is an important antioxidant in the mitochondrial membrane and

the LDL particle. In LDL, lipid peroxidation remains slow while CoQ10 is present, but
once it is used up, it increases 35-fold even in the presence of vitamin E, carotenoids,
and other antioxidants (108). CoQ10 protects against age-associated accumulation of
DNA damage in rats fed polyunsaturated sunflower oil, but even a dose equivalent to a
human taking over 50 milligrams per day, which can only be obtained by using
supplements or by eating two to three servings of heart meat every day, is less effective
than substituting monounsaturated olive oil for the dietary fat (109).

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 28/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

Preformed vitamin A or retinol is also a powerful antioxidant, although its mechanism

of action is less clear. It is 2.5 times as effective as vitamin E at preventing dioxin-
induced mortality and, unlike vitamin E, has a sparing effect on glutathione peroxidase,
the enzyme that uses glutathione to neutralize free radicals (110). Cod liver oil contains
omega-3 fatty acids in combination with vitamins A and D, and should therefore be
safer than fish oil. This has not been tested directly, however.

One study in type 1 diabetic rats showed that supplementation with cod liver oil at a
dose equivalent to a human taking 7.5 teaspoons per day prevented the increase in lipid
peroxidation seen in diabetes, at least in part by decreasing the levels of glucose and
lipids in the blood, but had no effect on lipid peroxidation in non-diabetic rats (111).
Unfortunately, the authors did not report the composition of the diet or whether the cod
liver oil was substituted for a different oil in the untreated rats. Mice injected with the
kidney-damaging compound daunomycin experienced an increase in
renal lipid peroxidation, a decrease in renal glutathione peroxidase, and renal tissue
damage when fed on soybean oil but were mostly resistant to these changes when fed on
cod liver oil (112). On the other hand, cod liver oil fed to healthy rats for ten weeks as
five percent of the diet increased urinary excretion of MDA at least as much as even
larger doses of corn oil when compared to a hydrogenated coconut oil control. The
effect was only seen when the rats were fasted for 48 hours, suggesting either that lipid
peroxidation increases when free fatty acids are released, or that lipid peroxides formed
in the membrane are released with other free fatty acids during fasting and further
degraded to MDA (113). None of these studies reported the vitamin A concentration of
the cod liver oil.

Until high-quality human data are obtained examining the effect of cod liver oil on lipid
peroxidation and taking into account its vitamin content, it makes sense to use cod liver
oil instead of fish oil, but to use it only in the small amounts necessary to obtain needed
fat-soluble vitamins or to obtain a modest amount of DHA during pregnancy.

The cell uses a wide array of lipid-soluble and water-soluble nutrients, enzymes, and
related compounds to defend itself from oxidative stress. All of them are important to
preventing lipid peroxidation. The available evidence, however, indicates that dietary
PUFA represent an independent contributor to oxidative stress and dietary antioxidants
can only partially compensate for their deleterious effects. It therefore seems wise to

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 29/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

limit PUFA intake to as close to the minimal requirement as is practical, while still
maintaining an appealing and nutrient-rich diet.

Dietary Conclusions
The conventional terminology labels linoleate and ALA “essential fatty acids” because
they cannot be produced by the body. This information is actually outdated, because
green leafy vegetables contain modest amounts of 16-carbon omega-6 and omega-3
PUFA that can be directly elongated to the so-called essential fatty acids (17), and there
is some evidence that the body might be able to convert lauric acid
to ALA (114). A more sensible terminology would label only those fatty acids the body
actually needs as essential. The evidence is conclusive that arachidonate is essential and
very compelling that DHA is essential. The case for the essentiality of other fatty acids
is presently unconvincing. Arachidonate and DHA might be “conditionally essential” in
that they need not be supplied directly if precursor fatty acids are supplied in the diet,
but there is no evidence that the precursors themselves are essential.

The best sources of EFA are liver, egg yolk, and butter, especially from grass-fed
animals. These contain preformed arachidonate and DHA, as well as smaller amounts of
precursor fatty acids. On a diet low in vitamin B6, our bodies will effectively convert the
rancid and total PUFA and rich in calcium, biotin and precursor fatty acids into
additional arachidonate and DHA. On a diet low in sugar and rich in essential minerals,
the requirement for EFA during periods of growth is likely to be well under 0.5 percent
of calories if supplied by animal fats and well under 0.1 percent of calories if supplied
completely by liver.

Women who are hoping to conceive, or who are pregnant or lactating should consume at
least twice this amount of EFA. Cod liver oil is an excellent source of additional DHA,
but only one or two teaspoons per day should be used. Because it contains EPA, cod
liver oil should be balanced with liver and plenty of egg yolks. Egg yolks are also the best
source of choline, and animal experiments suggest that a great excess of choline during
pregnancy provides lifelong benefits to the child’s nervous system and mental
functioning.

Cod liver oil is also an excellent source of fat-soluble vitamins. Weston Price
supplemented growing children with three-quarters of a teaspoon of cod liver oil per

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 30/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

day combined with an equal amount of a butter oil concentrate and obtained dramatic
improvement in dental health. Growing children might benefit from a small amount of
DHA in the diet, especially while they are very young and their brains are still
developing. As for pregnant women, the amount should be kept small and balanced by a
diet that includes liver and is rich in egg yolks.

Vegetarians and those consuming limited amounts of animal fat should be aware that
EFA deficiency remains a possibility for those who do not efficiently desaturate and
elongate precursor PUFA. If they experience any symptoms of EFA deficiency such as
scaly skin, hair loss, or infertility, they should try increasing their intake of B6 or animal
fat.

Lard is also a good source of EFA, but because it is high in linoleate, it should only be
used in small amounts. Lamb and beef tallow are lower in total PUFA and can therefore
be used as staple fats, but, like lard, will provide some preformed arachidonate. Olive oil
and red palm oil contain modest amounts of linoleate and can be used in small amounts.
Red palm oil is an excellent source of vitamin E and carotenes. Coconut and macadamia
nut oils are very low in PUFA and can be used in larger amounts, but they cannot be
substituted for animal fats that supply EFA. PUFA-rich vegetable oils and fish oils
should be avoided.

While arachidonate and DHA must be supplied by food, the body easily synthesizes
saturated and monounsaturated fats from carbohydrates. The benefit of consuming
these fats, then, is to avoid an excess of PUFA and carbohydrate and to supply taste and
satiety. The evidence presented herein suggests that the ideal diet contains a mix of
saturated and monounsaturated fat, with only a very small amount of PUFA provided
primarily by animal fats such as lard, liver and egg yolks. Such a diet will provide the
required amount of EFA while simultaneously avoiding an excess of PUFA and the
ravages of oxidative stress such an excess brings with it and thus, we hope, provide good
health into old age.

Sidebars, Figures, and Tables are Found

Below the References

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 31/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

References

1. 1. Carpenter KJ, Harper AE. Evolution of Knowledge of Essential Nutrients. In:

Shils ME, et al., eds. Modern Nutrition in Health and Disease: Tenth Edition.
Baltimore, MD; Philadelphia, PA: Lippincott Williams & Wilkins (2006) pp. 3-9.

2. Osborne TB, Mendel LB. Growth on Diets Poor in True Fats. J Biol Chem.
1920;45(1):145-152.

3. Holman RT. George O. Burr and the Discovery of Essential Fatty Acids. J Nutr.
1988;118:535-40.

4. Burr GO, Burr MM. A New Deficiency Disease Produced by the Rigid Exclusion of
Fat from the Diet. J Biol Chem. 1929;82(2):345-67.

5. Burr GO, Burr MM. On the Nature and Role of the Fatty Acids Essential in
Nutrition. J Biol Chem. 1930; 86(2):587-621.

6. Holman RT. The Ratio of Trienoic:Tetraenoic Acids in Tissue Lipids as a Measure

of Essential Fatty Acid Requirement. J Nutr. 1960:70(3):405-10.

7. Turpeinen O. Further Studies on the Unsaturated Fatty Acids Essential in

Nutrition. J Nutr. 1937;15(4):

8. Widmer C, Holman RT. Polyethenoid Fatty Acid Metabolism. II. Deposition

of Polyunsaturated Fatty Acids in Fat-Deficient Rats Upon Single Fatty Acid
Supplementation. Arch Biochem. 1950;25(1):1-12.

9. Holman RT. Essential Fatty Acid Deficiency. A long scaly tale. Prog Lipid Res.
1968;9:275-348.

10. Witten PW, Holman RT. Polyethenoid Fatty Acid Metabolism. VI. Effect
of Pyridoxine on Essential Fatty Acid Conversions. Arch Biochem Biophys.
1952;41(2):266-73.

11. Ziboh VA, Hsia SL. Effects of prostaglandin E2 on rat skin: inhibition of sterol
ester biosynthesis and clearing of scaly lesions in essential fatty acid deficiency. J
Lipid Res. 1972:13:458-66.

12. Agrawal R, Daniel EE. Control of gap junction formation in canine trachea by
arachidonic acid metabolites. Am J Physiol. 1986;250(3Pt1):C495-505.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 32/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

13. Civitelli R, Ziambaras K, Warlow PM, Lecanda F, Nelson T, Harley J, et al.

Regulation of connexin43 expression and function by prostaglandin E2 (PGE2) and
parathyroid hormone (PTH) in osteoblastic cells. J Cell Biochem. 1998;68(1):8-21.

14. Blikslager AT, Roberts MC, Rhoads MJ, Argenzio RA. Prostaglandins I2 and E2
Have a Synergistic Role in Rescuing Epithelial Barrier Function in Porcine Ileum. J
Clin Invest. 1997;100:1928-33.

15. Maass K, Ghanem A, Kim J-S, Manuela S, Urschel S, Kirfel G, et al. Defective
Epidermal Barrier in Neonatal Mice Lacking the C-Termianl Region of
Connexin43. Mol Biol Cell. 2004;15:4597-608.

16. Yuki T, Haratake A, Koishikawa H, Morita K, Miyachi Y, Inoue S. Tight junction

proteins in keratinocytes: localization and contribution to barrier function. Exp
Dermatol. 2007;16(4):324-30. And references therein.

17. Jones PJH, Kubow S. Lipids, Sterols, and their Metabolites. In: Shils ME, et
al., eds. Modern Nutrition in Health and Disease: Tenth Edition. Baltimore, MD;
Philadelphia, PA: Lippincott Williams & Wilkins (2006) pp. 92-122.

18. Sinclair AJ, Attar-Bashi NM, Li D. What Is the Role of α-Linolenic Acid for
Mammals? Lipids 2002;37:1113-23.

19. Hansen S, Jensen B. Essential function of linoleic acid esterified in

acylglucosylceramide and acylceramide in maintaining the epidermal water
permeability barrier. Evidence from feeding studies with oleate, linoleate,
arachidonate, columbinate, and α-linolenate. Biochimica et Biophysica Acta.
1985;834:357-63.20

20. Hansen HS, Jensen B, von Wettstein-Knowles P. Apparent in vivo retroconversion

of dietary arachidonic to linoleic acid in essential fatty acid-deficient rats.
Biochimica et Biophysica Acta. 1986;878:284-87.

21. Melton JL, Wertz PW, Swartzendruber DC, Downing DT. Effects of essential fatty
acid deficiency on epidermal O-acylsphingolipids and transepidermal water loss in
young pigs. Biochimica et Biophysica Acta. 1987;921:191-7.

22. Panos TC. Effects of fat deficiency on the endocrine system in rats. J Pediatr.
1963;63:1167-78.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 33/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

23. Wesson LG, Burr GO. The Metabolic Rate and Respiratory Quotients of Rats on a
Fat-Deficient Diet. J Biol Chem. 1931;91:525-39. And the references therein.

24. Morris DM, Panos TC, Finerty JC, Wall RL, Klein GF. Relation of thyroid activity to
increased metabolism induced by fat deficiency. J Nutr. 1957;62(1):119-28.

25. Greenberg SM, Deuel Jr. HJ. The protective effect of high fat diets on immature rats
fed thyroid. J Nutr. 1950;42(2):279-83.

26. Wiersinga WM, Chopra IJ, Teco GNC. Inhibition of Nuclear T3 Binding by Fatty
Acids. Metabolism. 1988;37(10):996-1002. And the references therein.

27. Mazzachi BC, Kennedy JA, Wellby ML, Edwards AM. Effect of Fatty Acids on Rat
Liver Nucelar T3-Receptor Binding. Metabolism. 1992;41(7):788-92.

28. Yamamoto N, Li Q-L, Mita S, Morisawa S, Inoue A. Inhibition of Thyroid Hormone

Binding to the Nuclear Receptor by Mobilization of Free Fatty Acids. Horm Metab
Res. 2001;33:131-7.

29. Ershoff BH. Protective effects of soybean meal for the immature hyperthyroid rat. J
Nutr. 1949;32(9):259-81.

30. Overby LR, Frost DV, Fredrickson RL. The antithyrotoxic factor of liver.
II. Comparative activities of defatted liver residue and various fats. J Nutr.
1959;68(2):251-63.

31. Seitz HJ, Müller MJ, Soboll S. Rapid thyroid-hormone effect on mitochondrial and
cytosolic ATP/ADP ratios in intact liver cell. Biochem J;1985;227:149-53.

32. Fontaine EM, Moussa M, Devin A, Garcia J, Ghisolfi J, Rigoulet M, Leverve XM.
Effect of polyunsaturated fatty acids deficiency on oxidative phosphorylation in rat
liver mitochondria. Biochim Biophys Acta. 1996;1276(3):181-7.

33. Piquet MA, Fontaine E, Sibille B, Filippi C, Keriel C, Leverve XM. Uncoupling
effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on
glycerol metabolism. Biochem J. 1996;317(Pt3):667-74.

34. Nogueira V, Piquet M-A, Devin A, Fiore C, Fontaine E, Brandolin G, et al. J

Bioenerg Biomembr. 2001;33(1):53-61.

35. NutritionData: know what you eat. http://www.nutritiondata.com. Accessed March

20, 2008.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 34/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

36. Hansen AE, Wiese HF, Boelsche AN, Haggard ME, Adam DJD, Davis H. Role of
linoleic acid in infant nutrition. Clinical and chemical study of 428 infants fed on
milk mixtures varying in kind and amount of fat. Pediatrics. 1963;31(Suppl 1):171-
92.

37. Hansen AE, Haggard ME, Boelsche AN, Adam DJD, Wiese HF. Essential Fatty
Acids in Infant Nutrition. III. Clinical Manifestations of Linoleic Acid Deficiency. J
Nutr. 1958;66(4):565-76.

38. Bieri JG, Prival EL. Linoleic Acid Requirement of the Chick. J Nutr. 1966;90(4):428-
432.

39. Hill EG, Warmanen EL, Silbernick CL, Holman RT. Essential Fatty Acid Nutrition
in Swine. I. Linoleate Requirement Estimated From Triene:Tetraene Ratio of Tissue
Lipids. J Nutr. 1961;74(3):335-41.

40. Sewell RF, McDowell LJ. Essential Fatty Acid Requirement of Young Swine. J Nutr.
1966;89(1):64-8.

41. Leat WMF. Studies on pigs reared on diets low in tocopherol and essential fatty
acids. Brit J Nutr. 1961;15:259-69

42. Leat WMF. Essential fatty-acid (E.F.A.) requirement of the pig. Proc Nutrition Soc.
1959;18:xxxi-xxxii.

43. Brown WR, Hansen AE, Burr GO, McQuarrie I. Effects of prolonged use of
extremely low-fat diet on an adult human subject. J Nutr. 1938;16(6):511-23.

44. Fleming CR, Smith LM, Hodges MD. Essential fatty acid deficiency in adults
receiving total parenteral nutrition. Am J Clin Nutr. 1976;29:976-83.

45. Wene JD, Connor WE, DenBesten L. The Development of Essential Fatty Acid
Deficiency in Health Men Fed Fat-Free Diets Intravenously and Orally. J Clin
Invest. 1975;56:127-34.

46. Barki VH, Nath H, Hart EB, Elvehjem CA. Production of essential fatty acid
deficiency symptoms in the mature rat. Proc Soc Exp Biol Med. 1947;66:474-8.

47. Quackenbush FW, Kummerow FA, Steenbock H. The effectiveness of linolenic

arachidonic, and linolenic acids in reproduction and lactation. J Nutr.
1942;24(3):213- 224.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 35/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

48. Nakamura MT, Nara TY. Structure, Function, and Dietary Regulation of Δ6, Δ5, and
Δ9 Desaturases. Annu Rev Nutr. 2004;24:345-76.

49. Casal J, Holman R. The Effect of Kind of Dietary Carbohydrate upon the
Composition of Liver Fatty Acids in the Rat. J Am Oil Chem Soc. 1965;42(12):1134-
7.

50. Chaudhary DP, Boparai RK, Bansal DD. Implications of oxidative stress in high
sucrose low magnesium diet fed rats. Eur J Nutr. 2007;46:383-90.

51. 51. Hill EG, Warmanen EL, Hayes H, Holman RT. Effects of Essential Fatty Acid
Deficiency in Young Swine. Proc Soc Exp Biol Med. 1957;95(2):274-8.

52. Holman RT. ω3 and ω6 Essential Fatty Acid Status in Human Health and Disease.
In: Yehuda S, Mostofsky DI, eds., Handbook of Essential Fatty Acid Biology:
Biochemistry, Physiology, and Behavioral Neurobiology. Totaway, NJ: Humana
Press (1997) pp. 139-82.

53. Fulco AJ, Mead JF. Metabolism of Essential Fatty Acids. VIII. Origin of 5,8,11-
Eicosatrienoic Acid in the Fat-Deficient Rat. J Biol Chem. 1959;234:1411-6.

54. Paulsrud JR, Pensler L, Whitten CF, Steawrt S, Holman RT. Essential fatty
acid deficiency in infants induced by fat-free intravenous feeding. Am J Clin Nutr.
1972;25:897-904.

55. Adkisson HD, Risener Jr. FS Zarrinkar PP, Walla MD, Christie WW, Wuthier RE.
Unique fatty acid composition of normal cartilage: discovery of high levels of n-9
eicosatrienoic acid and lowlevels of n-6 polyunsaturated fatty acids. FASEB J.
1991;5:344-53.

56. Holman RT, Peifer JJ. Acceleration of Essential Fatty Acid Deficiency by Dietary
Cholesterol. J Nutr. 1960;70(3):411-17.

57. Peifer JJ, Holman RT. Effect of Saturated Fat Upon Essential Fatty Acid
Metabolism of the Rat. J Nutr. 1959;68(1):155-68.

58. Brownsey RW, Boone AN, Elliott JE, Kulpa JE, Lee WM. Regulation of acetyl- CoA
carboxylase. Biochem Soc. Trans. 2006;34(Pt 2):223-7.

59. Marra CA, de Alaniz MJT. Calcium Deficiency Modifies Polyunsaturated Fatty
Acid Metabolism in Growing Rats. Lipids. 2000;35:983-90.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 36/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

60. Eder K. The Effects of a Dietary Oxidized Oil on Lipid Metabolism in Rats. Lipids.
1999;34:717-25.

61. Kramer TR, Briske-Anderson M, Johnson SB, Holman RT. Influence of Reduced
Food Intake on Polyunsaturated Fatty Acid Metabolism in Zinc-Deficient Rats. J
Nutr. 1984;114:1224-30.

62. Cunnane SC, Yang J. Zinc deficiency impairs whole-body accumulation of

polyunsaturates and increases the utilization of [1-14C]linoleate for de novo lipid
synthesis in pregnant rats. Can J Physiol Pharmacol. 1995;73(9):1246-52. [Abstract].

63. Holman RT. The Slow Discovery of the Importance of ω3 Essential Fatty Acids in
Human Health. J Nutr. 1998;128:427S-33S.

64. Holman RT, Johnson S, Hatch TF. A case of human linolenic acid deficiency
involving neurological abnormalities. Am J Clin Nutr. 1982;35:617-23.

65. Forrest GL, Futterman S. Age-related changes in the retinal capillaries and the fatty
acid composition of retinal tissue of normal and essential fatty acid-deficient
rats. Invest Ophthalmol. 1972;11(9):760-4. This paper showed no effect of diet on
DHA content in Table I, and has been interpreted by these and other authors as
such. However, table II shows that “when the polyunsaturated fatty acids of the
retina were further examined,” diet had a dramatic effect on the ratio of DHA to its
omega-6 isomer, DPA. The only way to reconcile Table I to Table II is to conclude
that table I labels as “DHA,” the combination of DHA+DPA according to the
preliminary analysis of fatty acids that did not take into account the position of the
double bonds.

66. Tinoco J, Miljanich P, Medwadowski B. Depletion of docosahexaenoic acid

in retinal lipids of rats fed a linolenic acid-deficient, linoleic acid-containing diet.
Biochim Biophys Acta. 1977;486:575-8.

67. Mohrhauer H, Holman RT. Alteration of the fatty acid composition of brain lipids
by varying levels of dietary essential fatty acids. J Neurochem. 1963;10:523-30.

68. Tinoco J, Babcock R, Hincenbergs I, Medwadowski B, Miljanich P. Linolenic Acid

Deficiency: Changes in Fatty Acid Patterns in Female and Male Rats Raised on a
Linolenic Acid-Deficient Diet for Two Generations. Lipids. 1978;13(1):6-17.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 37/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

69. Neuringer M, Connor WE, van Petten C, Barstad L. Dietary Omega-3 Faty Acid
Deficiency and Visual Loss in Infant Rhesus Monkeys. J Clin Invest. 1984;73:272-6.

70. Neuringer M, Connor WE, Lin DS, Barstand L, Luck S. Biochemical and functional
effects of prenatal and postnatal ω3 fatty acid deificiency on retina and brain in
rhesus monkeys. Proc Natl Acad Sci USA. 1986;83:4021-5.

71. Innis SM. Dietary (n-3) Fatty Acids and Brain Development. J Nutr. 2007;137:855-9.

72. Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates
in adults: implications for their dietary essentiality and use as supplements. Appl
Physiol Nutr Metab. 2007;32:619-34.

73. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal
supplementation with very-long-chain n-3 fatty acids during pregnancy and
lactation augments children’s IQ at 4 years of age. Pediatrics. 2003; 111(1):e39-44.

74. Anderson GJ. Developmental sensitivity of the brain to dietary n-3 fatty acids. J
Lipid Res. 1994; 35:165-11.

75. Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, et al. Docosahexaenoic
acid protects from dendritic pathology in an Alzehimer’s disease mouse model.
2004;43(5):633-45.

76. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. Neuroprotectin D1: a
docosahexaenoic acid-derived docosatriene protects human retinal pigment
epithelial cells from oxidative stress. Proc Natl Acad Sci USA. 2004;101(22):8491-6.

77. Crawford MA, Bloom M, Broadhurst CL, Schmidt WF, Cunnane SC, Galli C, et al.
Evidence for the Unique Function of Docosahexaenoic Acid During the Evolution
of the Modern Hominid Brain. Lipids. 1999;34:S39-S47.

78. Pankiewicz E, Cretti A, Ronin-Walknowska E, Czeszvnska M-B, Konefat H,

Hnatyszyn G. Maternal adipose tissue, maternal and cord blood essential fatty acids
and their long-chain polyunsaturated derivatives composition after elective
caesarean section. Early Hum Dev. 2007;83(7):459-64.

79. Neuringer M, Anderson GJ, Connor WE. The Essentiality of N-3 Fatty Acids for the
Development and Function of the Retina and Brain. Ann Rev Nutr. 1988;8:517-41.

80. Serhan CN. Novel omega-3-derived local mediators in anti-inflammation and

resolution. Pharmacol Ther. 2005;105(1):7-21.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 38/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

81. Sinclair H. History of EFA and their prostanoids: some personal reminiscences.
Prog Lipids Res. 1986;25:667-72.

82. Peat R. “Oils in Context.” http://raypeat.com/articles/nutrition/oils-in-context.

shtml. Published 2006. Accessed April 3, 2008.

83. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male

factor infertility: an update. Am J Reprod Immunol. 2008;59(1):2-11. [Abstract]

84. Carlson SE. Arachidonic Acid Status of Human Infants: Influence of Gestational
Age at Birth and Diets with Very Long Chain n-3 and n-6 Fatty Acids. J Nutr.
1996;126:1092S-8S.

85. Yehuda S, Carasso RL. Modulation of learning, pain thresholds, and

thermoregulation in the rat by preparations of free purified α-linolenic and linoleic
acids: Determination of the optimal ω3-to-ω6 ratio. Proc Natl Acad Sci USA.
1993;90:10345-9.

86. Cunnane SC, Belza K, Anderson MJ, Ryan MA. Substantial carbon recycling from
linoleate into products of de novo lipogenesis occurs in rat liver even under
conditions of extreme dietary linoleate deficiency. J Lipid Res. 1998;39:2271-6.

87. Taha AY, Ryan MA, Cunnane SC. Markedly Raised Intake of Saturated and
Monounsaturated Fatty Acids in Rats on a High-Fat Ketogenic Diet Does Not
Inhibit Carbon Recycling of 13C-α-Linolenate. Lipids. 2006;41(10):933-5.

88. Gower JD. A role for dietary lipids and antioxidants in the activation of
carcinogens. Free Rad Biol Med. 1988;5:95-111.

89. Saito M, Kubo K. Relationship between tissue lipid peroxidation and

peroxidizability index after alpha-linolenic, eicosapentaenoic, or docosahexaenoic
acid intake in rats. Br J Nutr. 2003;89(1):19-28.

90. Diniz YS< Cicogna AC, Padovani CR, Santana LS, Faine LA, Novelli EL. Diets rich
in saturated and polyunsaturated fatty acids: metabolic shifting in cardiac health.
Nutrition. 2004;20(2):230-4.

91. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An

interpretive history for the cholesterol controversy: part II: the early evidence
linking hypercholesterolemia to coronary disease in humans. J Lipid Res.
2005;46(2):179-90.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 39/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

92. Kritchevsky D. Cholesterol and Other Dietary Sterols. In: Shils ME, et al., eds.
Modern Nutrition in Health and Disease: Tenth Edition. Baltimore,
MD;Philadelphia, PA: Lippincott Williams & Wilkins (2006) p. 125.

93. Laufs U, Fata VL, Plutzky J, Liao JK. UPregulation of Endotelial Nitric Oxide
Synthase by HMG CoA reductase Inhibitors. Circulation. 1998;97:1129-35.

94. Tontonoz P, Nagy L, Alvarez JGA, Thomazy VA, Evans RM. PPARγ Promotes
Monocyte/Macrophage Differentiation and Uptake of Oxidized LDL. Cell.
1998;93:241-52.

95. Nagy L, Tontonoz P, Alvarez J, Chen H, Evans RM. Oxidized LDL regulates
macrophage gene expression through ligand activation of PPARγ. Cell. 1998;93:229-
40.

96. Nenseter MS, Drevon CA. Dietary polyunsaturates and peroxidation of low density
lipoprotein. Curr Opin Lipidol. 1996;7(1):8-13.

97. Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrates, and
progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr.
2004;80:1175-84.

98. Knopp RH, Retzlaff BM. Saturated fat prevents coronary artery disease? An
American paradox. Am J Clin Nutr. 2004;80:1102-3.

99. Marchioli R, Levantesi G, Macchia A, Maggioni AP, Marfisi RM, Silletta MG.
Antiarrhythmic Mechanisms of n-3 PUFA and the Results of the GISSI-
Prevenzione Trial. J Membrane Biol. 2005;206:117-28.

100. Burr ML, Dunstan FD, George CH. Is fish oil good or bad for heart disease?
Two trials with apparently conflicting results. J Membr Biol. 2005;206(2):155-83.

101. Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of Different
Antilipidemic Agents and Diets on Mortality. Arch Intern Med. 2005;165:725-30.

102. Ronis MJ, Korourian S, Zipperman M, Hakkak R, Badger TM. Dietary saturated fat
reduces alcoholic hepatotoxicity in rats by altering fatty acid metabolism and
membrane composition. J Nutr. 2004; 13(4):904-12.

103. Rodríguez RR, Cattáneo P, Houssay BA, Uno B. Unsaturated fatty acids and alloxan
diabetes. J Nutr. 1953;51(3):441-8.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 40/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

104. QuilesJL, Ochoa JJ, Ramirez-Tortosa C, Battino M, Huertas JR, Martín Y, Mataix J.
Dietary fat type (virgen olive vs. sunflower oils) afects age-related changes in DNA
double-strand-breaks, antioxidant capacity and blood lipids in rats. Exp Gerontol.
2004;39(8):1189-98.

105. Spiteller P, Spiteller G. 9-Hydroxy-10,12-octadecadienoic acid (9-HODE)

and 13-hydroxy-9,11-octadecadienoic acid (13-HODE): excellent markers for lipid
peroxidation. Chem Phys Lipids. 1997;89:131-9.

106. Witting L. The role of polyunsaturated fatty acids in determining vitamin E

requirement. Ann NY Acad Sci. 1972;203:192-8.

107. Allard JP, Kurian R, Aghdassi E, Muggli R, Royall D. Lipid Peroxidation During n-3
Fatty Acid and Vitamin E Supplementation in Humans. Lipids. 1997;32:535-41.

108. Stocker R, Bowry VW, Frei B. Ubiquinol-10 protects human low density lipoprotein
more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl
Acad Sci USA. 1991;88(5):1646-50.

109. Quiles JL, Ochoa JJ, Huertas JR, Mataix J. Coenzyme Q supplementation protects
from age-related DNA double-strand breaks and increases lifespan in rats fed on a
PUFA-rich diet. Exp Gerontol. 2004;39(2):189-94.

110. Stohs SJ, Hassan MQ, Murray WJ. Effects of BHA d-alpha-tocopherol and retinol
acetate on TCDD-mediated changes in lipids peroxidation, glutathione peroxidase
activity and survival. Xenobiotica. 1984;14(7):533-7.

111. Hünkar T, Aktan F, Ceylan A, Karasu C, and (Antioxidants in Diabetes-

Induced Complications) The ADIC Study Group. Effects of cod liver oil on tissue
antioxidant pathways in normal and streptozotocin-diabetic rats. Cell Biochem
Funct. 2002;20:297-302.

112. Ohtake T, Kimura M, Takemura H, Hishida A. Effects of Dietary Lipids on

Daunomycin-Induced Nephropathy in Mice: Comparison Between Cod Liver Oil
and Soybean Oil. Lipids. 2002;37:359-66.

113. Dhanakoti SN, Draper HH. Response of urinary malondialdehyde to factors that
stimulate lipid peroxidation in vivo. Lipids. 1987; 22(9):543-6.

114. Legrand P, Catheline D, Rioux V, Durand G. Lauric Acid is Desaturated to 12:1n-3

by Hepatocytes and Rat Liver Homogenates. Lipids. 2002;37:569-72.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 41/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

1 Figure 1. a. Fatty acids consist of a hydrocarbon chain with varying numbers of methylene
groups (CH2) linked together by their carbon atoms, a carboxyl (COOH) end, and a methyl
(CH3) end. Unsaturated fatty acids have one or more double bonds between two carbon atoms
that are each missing one hydrogen atom (not shown). b. Fatty acids are enumerated by their
number of carbons on the left of the colon, their number of double bonds on the right of the
colon, and the position of their first double bond counting in from the methyl end following
the hyphen. All other double bonds are spaced three carbons apart, moving in the direction of
the carboyxl end. For example, C18:2n-6 has 18 carbons and two double bonds, the first being
between the sixth and seventh carbons in from the methyl end, the second being between the
tenth and eleventh carbons in from the methyl end. Enzymes modify the carboxyl end of the
fatty acid, so the position of the first double bond with respect to the methyl end never
changes. Thus, desaturated and elongated fatty acids fall into distinct families sharing the
position of this bond with their precursors, and are thus designated. On the other hand, the
desaturase enzymes place double bonds in specific positions with respect to the carboyxl end,
and are thus designated. The enzymes are indicated at the top, with nutrients necessary for
the reaction in parentheses. Biotin is necessary for the production of the carbon units added
by elongase, while the precise role of B6 in supporting D6D is unclear. Abbreviations: D6D --
delta-6 desaturase; D5D -- delta-5 desaturase; DGLA -- dihomo-gamma-linolenic acid; DPA --
docosapentaenoic acid; EPA -- eicosapentaenoic acid; DHA -- docosahexaenoic acid.

2 Figure 2. EFA Requirements Across Species Are Exceedingly Low

The essential fatty acid (EFA) requirement is shown for different species as a percentage of
calories and reflects the total EFA consumed including any provided by the basal diet. All
species tested are young and in a state of rapid growth. Where the lowest tested amount was
found curative, a less-than-or-equal-to sign (≤) is used. Where the interval between the lowest
effective amount and the highest ineffective amount is large, the two amounts are presented
as a range. The requirement is lowest in references 41 and 42 wherein the basal diet was
composed of real foods, in reference 4 wherein the EFA was supplied by liver, and in

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 42/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

reference 39 wherein the basal diet contained a high concentration of vitamin B6 (four times
as much as supplied in reference 40 and twice as much as contained in liver). The requirement
for growing animals appears to be less than one percent in all species and less than 0.5
percent in most circumstances.

3 Is Linoleate Essential to Skin Health?

Current reviews (17, 18) claim that linoleate rather than arachidonate is the fatty acid that
cures the dermatitis associated with EFA deficiency. Humans and other animals possess
enzymes that convert linoleate to arachidonate and arachidonate to a number of different
products called prostaglandins, including PGE1 and PGE2. In 1972, researchers from the
University of Miami School of Medicine showed that while abdominal injection of PGE2 was
ineffective, its topical application completely cured EFA-deficiency dermatitis (11). The effect
was dose-dependent and limited to the local area to which the prostaglandin was applied.

This study seems to have been overlooked in favor of older studies showing that oral delivery
or injection of PGE1 had no effect. Current reviews (17, 18) make no mention of this study and
instead cite Danish research from the 1980s that implausibly attributed the protection of
omega-6 fatty acids against EFA-deficiency dermatitis to linoleate. The Danish group showed

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 43/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

that certain fatty acid derivatives that accumulate in the skin barrier ordinarily contain
primarily linoleate but in EFA deficiency contain primarily oleate, the fatty acid that
predominates in olive oil and the major unsaturated fatty acid that the body can synthesize
from carbohydrate. All of the fatty acids that resolved the water loss increased the amount of
linoleate found in the skin barrier, but the degree to which they increased this linoleate did
not correlate with the degree to which they cured the water loss (19).

Puzzled by the fact that arachidonate cured the water loss but was not known to be converted
backwards to linoleate, the researchers made a poor attempt to demonstrate this backwards
conversion: they fed linoleate and arachidonate that were both labeled with radioactive
tracers together and found a higher radio-labeled linoleate-to-arachidonate ratio in the skin
barrier than they fed in the diet (20). The simplest explanation of their results was that
linoleate is preferentially incorporated into the skin barrier, but they claimed to have
observed “apparent in vivo retroconversion” of arachidonate to linoleate. They could have
easily shown this by feeding radio-labeled arachidonate alone and seeing if any radio-labeled
linoleate turned up – but they did not. One year later, researchers from the University of Iowa
College of Medicine showed that the incorporation of oleate derivatives into the skin barrier
during EFA deficiency had no effect on the barrier’s structural properties (21) and to this day,
current reviews make no claims that arachidonate can be converted to linoleate (17).

The hypothesis was implausible from the get-go because arachidonate is at least three times
more effective at curing the dermatitis than linoleate (7), and vitamin B6, which increases the
conversion of linoleate to arachidonate, dramatically improves the dermatitis (10). If linoleate
were the curative fatty acid, it should have proved more effective than arachidonate even if
arachidonate were converted backwards to linoleate – and vitamin B6 should have made the
dermatitis worse.

4 Changes to the Endocrine System in EFA Deficiency

A number of different changes occur to the endocrine system in EFA deficiency. In females,
ovulation ceases, resulting in a decreased production of estrogen and progesterone by the
ovaries. Males suffer from impaired sex interest, testicular degeneration, and cessation of
sperm production. Both sexes suffer microscopic changes to tissues that are characteristic of
castration, and in males they are virtually completely restored by the administration of
testosterone, suggesting that they are mediated by impaired production of the hormone. In
both sexes the thyroid gland is smaller, while the adrenal glands are smaller in females but
larger in males. The changes in the weight of the adrenal glands in both sexes are consistent
with a deficiency of their respective sex hormones and in males can be rescued with

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 44/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

testosterone therapy. The male adrenal glands are unable to respond to stressors such as
fracture, surgery, fasting and cold temperature. Despite the decrease in the size of the thyroid
no major changes in its production of thyroid hormone occur. There is conflicting evidence,
however, regarding the possibility that the body tissues of EFA-deficient rats are much more
sensitive to the hormone (22). This possibility is critically reviewed in the sidebar, Are EFA-
Deficient Rats Hypersensitive to Thyroid Hormone?

5 Are EFA-Deficient Rats Hypersensitive to Thyroid Hormone?

The earliest symptom of EFA deficiency is an increase in the metabolic rate represented by a
25-30 percent increase in oxygen consumption beginning within seven to fourteen days after
commencing the diet (17, 18). Some early investigators suggested that there was an
antagonism between the thyroid gland and unsaturated fatty acids because the double bonds
of these fatty acids can adsorb iodine that is needed for the synthesis of thyroid hormone.
Burr rejected this idea for three reasons: the feeding of unsaturated oils that had no curative
properties to EFA-deficient rats had no effect on their metabolic rate; curative oils raised it
even further; and in untreated rats the metabolic rate fell to normal or below normal after
four months even as the deficiency became more severe (23). Furthermore, research
conducted in 1956 showed that substantial loss of iodine occurred in EFA deficiency, probably
from evaporation through the skin, but that iodine uptake and metabolism by the thyroid
gland was normal (24). A paper published a few years earlier, however, suggested that EFA
deficiency may involve a markedly increased sensitivity of body tissues to thyroid hormone
(25). Feeding supplemental thyroid hormone to EFA-deficient rats in this study aggravated the
loss of bodyweight and increased mortality, though the authors did not examine the effect on
the metabolic rate or other parameters more specific to thyroid hormone. Extra B vitamins
aggravated the effect but the addition of 30 percent cottonseed oil by weight completely
eliminated it. Evidence for thyroid hormone hypersensitivity, however, is conflicting,
sometimes difficult to interpret, and ultimately unconvincing.

Because the dose of thyroid hormone in the cottonseed oil study was small, a 1963 review (22)
interpreted it as showing an extraordinary sensitivity to this hormone in EFA-deficient rats,
but offered no mechanism to explain the hypersensitivity. Additional test tube experiments
conducted in the 1980s showed that unsaturated free fatty acids inhibit the action of thyroid
hormone by three distinct mechanisms: they inhibit the binding of thyroid hormone to serum
transport proteins; they inhibit the enzymes that convert thyroid hormone to its active form;
and they inhibit the binding of thyroid hormone to its own nuclear receptor (26). Had Burr not
already shown that the elevation of the metabolic rate was specific to the lack of EFA and not
to the lack of unsaturated oils in general, one could have argued from this data that as dietary

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 45/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

unsaturated fatty acids reached a minimum, inhibition of thyroid signaling would also reach a
minimum and hypersensitivity would ensue. A closer look at the test tube data, however,
weakens this argument even further. The experiments demonstrating the inhibition of
transport and activation used serum from patients with “nonthyroidal illness,” a designation
given to non-hypothyroid patients with decreased levels of thyroid hormone in the blood;
these patients generally suffer from starvation, surgery, heart attack, systemic infection, or
other severe illnesses and have abnormally elevated concentrations of free fatty acids.
Moreover, these studies suggested that oleic acid was the most important inhibitor present in
the blood, and oleic acid is elevated in EFA deficiency. Unsaturated fatty acids are potent
inhibitors of thyroid hormone receptor binding in isolated nuclei, but the concentration
required for effective inhibition in whole cells is much higher than that needed in isolated
nuclei and is unlikely to be encountered in a healthy organism (27). And finally, while there is
evidence that the release of free fatty acids in response to stress can decrease thyroid receptor
signaling in the live animal (28), there is no data showing that dietary PUFA can modulate
this effect.

A more compelling interpretation of the cottonseed oil experiment is that excess thyroid
hormone increased the need for arachidonate, and cottonseed oil supplied it indirectly by
providing linoleate. Early experiments showed that toxic doses of thyroid hormone decreased
weight gain, increased mortality and in females inhibited ovarian development. These
experiments showed that thyroid hormone increased the need for most of the B vitamins, and
that yeast – which is rich in all B vitamins except B6 and B12 – counteracted the increase in
mortality, while desiccated and defatted liver not only decreased mortality but completely
reversed the failure to gain weight and the inhibition of ovarian development. Vitamin B12
counteracted the failure to gain weight when the diet consisted of soybean meal, but not
when it consisted of sucrose and casein, leading to the search for the “antithyrotoxic factor of
liver” whose need was especially apparent on the sucrose-casein diet (29). The “defatted” liver
still retained 7.5 percent of its fat (30), which would supply a substantial amount of
arachidonate in addition to the water-soluble B6, which would help the rats make
arachidonate from the linoleate in the liver extract and from the linoleate released from their
own fat stores. Various PUFA-rich vegetable oils all counteracted the toxic effect of thyroid
hormone, but lard was more effective than all of them (29). Lard has much less PUFA than
vegetable oils, but contains small amounts of preformed arachidonate. These experiments
strongly suggest that excess thyroid hormone aggravates the deficiency of arachidonate
produced by an EFA-deficient diet and that arachidonate itself is the “antithyrotoxic factor of
liver.”

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 46/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

The increase in the metabolic rate is probably a result of a defect in the electron transport
chain (ETC) that causes an inability to efficiently harness energy from food. The ETC exists in
the membrane of the mitochondria, the so-called “power house” of the cell. It takes hydrogen
ions and high-energy electrons from food and delivers them to oxygen, converting the oxygen
to water. The electrons give up energy in the process, which is used to pump hydrogen ions
across the membrane; the backflow of these ions drives a molecular turbine within the
enzyme ATP synthase, which uses the mechanical energy of the turbine to synthesize ATP,
much like a water turbine uses the flow of water to do work. The cell then uses ATP as its
basic energy currency.

ATP synthase normally fails to harness a portion of the hydrogen ion backflow, whose energy
is instead dissipated as heat. EFA deficiency and thyroid hormone both increase the
proportion of energy lost as heat, but in different ways: thyroid hormone increases the
activity of the ETC and the production of ATP so much that there is more overflow. This is
like pouring water from a bucket marked “food” into lots of cups marked “ATP”: the faster
you pour, the more you will spill – but the cups still get full (31). In EFA deficiency, the ETC
fails to efficiently pump the hydrogen ions in the first place and fails to make the ATP (32, 33).
This is like poking holes in the bucket – the water still spills, but the cups never get full. The
live organism engages in a number of adaptations to try to conserve its capacity to make ATP,
but the net availability of this critical energy molecule is still depleted (34).

The body temperature of the EFA-deficient animals never rises (23), probably because the
heat leaves as the water evaporates through the skin. The metabolic rate decreases to normal
or even below normal after four months, and is actually increased at all time points with
curative doses of EFAs (23); this is the opposite of what we would expect but probably occurs
because the measurement is adjusted for surface area rather than lean body mass, and part of
the loss of bodyweight in EFA deficiency may represent the wasting of metabolically active
muscle tissue and part of the gain during EFA repletion may represent the rebuilding of this
tissue. Thus thyroid hormone seems to aggravate EFA deficiency by increasing the need for
arachidonate, but a hypersensitivity to it does not seem to be involved in the basic
presentation of the deficiency. Rather, defective ETC functioning effectively leads to
starvation in spite of the increased food intake because of an inability to harness the energy
provided by it.

6 EFA Deficiency, Free Radicals, and High-Sugar Diets

George and Mildred Burr argued in their first paper that the deficiency disease their rats
developed on fat-free sucrose-casein diets had not been seen on fat-free meat residue-starch

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 47/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

diets because starch could not be sufficiently purified of EFA (4). But later research showed
that a diet that is nearly three quarters starch contains only 0.003 percent more calories as
linoleate than a diet that is nearly three quarters sucrose (49). This argument may have made
sense in 1929 when the Burrs had merely demonstrated the essentiality of fat, but made much
less sense once they demonstrated in 1930 that the curative fatty acid that could be present in
starch was linoleate, which is present in such a negligible proportion.

Rats fed an EFA-deficient diet based on starch for six weeks had over 50 percent more
arachidonate and over 80 percent more linoleate in their livers than rats fed an EFA deficient
diet based on sucrose (49), suggesting that sucrose increases the rate of degradation of these
fatty acids. High-sucrose diets increase lipid peroxidation in rats (50), a process whereby
PUFA are destroyed by oxygen and free radicals. Magnesium deficiency also increases lipid
peroxidation, and the effect of excess sucrose and magnesium deficiency is additive (50).
Magnesium deficiency exacerbates EFA deficiency in the pig (39, 51) but its effect has not
been investigated in the rat. It is likely that not only the high sucrose content of the EFA-
deficient diets but also the low content of magnesium and other protective minerals
contained within them greatly increased the need for essential fatty acids by promoting their
oxidative destruction.

Up until the 1960s there was the “lingering question” of whether high-sucrose diets were
somehow responsible for EFA deficiency. According to Ralph Holman (52), this question was
closed in 1965 when he and his colleague Jorge Casal showed that a biochemical marker
called the triene-to-tetraene ratio (see sidebar, Inflating the EFA Requirement with the
Triene-to-Tetraene Ratio) was increased in rats fed for six weeks on EFA-deficient diets
whether the carbohydrate portion was composed of sucrose, glucose, maltose or starch (49).
But they did not run the experiment long enough for the rats to develop dermatitis or any
other symptoms specific to EFA deficiency, and there was never any conclusive evidence that
this marker was sufficient to demonstrate true deficiency. Thus, the question remained open,
even though reviewers stopped asking it.

A number of animal studies following that of the Burrs demonstrated EFA deficiency using
glucose instead of sucrose (see Figure 2, EFA Requirements Across Species Are Exceedingly
Low). These diets tended to contain between 75 and 85 percent sugar by weight, which is like
an adult human eating some four pounds of sugar per day. WMF Leat of the Cambridge
School of Agriculture in the UK performed a much more sensible set of experiments using
dried skim milk supplemented with white fish meal as protein, palm-kernel cake as fat,
cassava as carbohydrate, and varying amounts of olive oil to supply the linoleate (41, 42). The
diet was thus lower in total carbohydrate and contained starch rather than sugar. He

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 48/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

prevented dermatitis with a much lower level of linoleate than was needed in other studies
and observed no effects of the deficiency on growth at all (see Figure 2, EFA Requirements
Across Species Are Exceedingly Low). An aggravating effect of sugar is further supported by
a human study in which eczema and other EFA deficiency symptoms were observed in infants
consuming most of their calories as corn syrup (36). Although the addition of butterfat was
necessary to completely cure the deficiency, the addition of 42 percent of calories as
hydrogenated coconut oil — containing only saturated fat and no EFA— substantially
ameliorated the eczema, probably because it replaced half of the corn syrup. The EFA
requirement is probably much lower, then, on diets that do not contain most of their calories
as refined sugars and possibly on diets that are lower in total carbohydrate.

7 Inflating the EFA Requirement with the Triene-to-Tetraene Ratio

Linoleate is converted to arachidonate by a series of enzymatic reactions that elongate the
fatty acid and introduce double bonds between its carbon atoms, a process called
desaturation. The same enzymes elongate and desaturate the omega-3 fatty acid ALA. When
linoleate and ALA are in short supply, however, these enzymes will convert oleic acid (oleate,
found in olive oil and produced by the body) into an elongated and desaturated product called
Mead acid – named after James Mead, who elucidated the pathway by which the body
synthesizes it (53). (See Figure 1) Mead acid is normally present in the body, but only in small
amounts. In EFA deficiency, arachidonate levels decrease as Mead acid levels rise. Ralph
Holman therefore proposed using the ratio of Mead acid to arachidonate as an index of EFA
deficiency. In organic chemistry, the suffix “-ene” refers to compounds with double bonds
between carbon atoms; since Mead acid contains three double bonds it is called a “triene” and
since arachidonate contains four double bonds it is called a “tetraene.” Mead acid is the
predominant triene in the body and arachidonate is the predominant tetraene. Holman
therefore promoted the use of an easier but virtually identical measurement called the triene-
to-tetraene ratio (6).

Holman propagated the idea that the “normal” triene-to-tetraene ratio is maximally
suppressed. In other words, the minimum requirement for EFA is the intake that maximizes
levels of arachidonate and minimizes levels of Mead acid. He never presented any evidence of
this; in fact, he presented evidence that flatly contradicted it. But this did not stop the use of
the maximally suppressed triene-to-tetraene ratio as the standard indicator of sufficiency
from spreading like wildfire through the research community.

Holman (6) fed various combinations and amounts of butter and cottonseed oil to rats on a
sucrose-casein diet and concluded that a ratio of 0.4 or less indicated the minimum

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 49/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

requirement of EFA for “normal” metabolism had been reached. Butterfat cured the
symptoms without providing enough EFA to meet the prescribed ratio, and Holman
suggested that the saturated fat masked the symptoms of deficiency. Ironically, the triene-to-
tetraene ratio of the butter was seven. This is almost 18 times the ratio that is supposed to
indicate the minimum EFA requirement has been met. Were the cows EFA-deficient?
Another study that reported the triene content of the diet (51) used purified casein and gelatin
whose small amount of residual fat had a ratio of 2.5, apparently also taken from “EFA-
deficient” cows.

A report showing that less than 0.2 percent of calories as EFA was sufficient for growth in
chickens concluded that the requirement was between one and two percent of calories based
on the triene-to-tetaraene ratio (38). Holman co-authored a paper showing that 0.23 percent
of calories as EFA was sufficient for growth in pigs and found no dermatitis even at less than
0.2 percent of calories, but concluded that the minimum requirement was two percent of
calories based on the triene-to-tetraene ratio (39). He later suggested that Australian
Aborigines are EFA-deficient because their ratio is elevated, but cited no physiological
consequences of the elevation (52).

Holman also co-authored a 1972 paper (54) that reported seven cases of supposed EFA
deficiency in human infants intravenously fed fat-free formulas. Six of the infants were fed for
17 to 36 days and displayed triene-to-tetraene ratios between 0.8 and 3.0 that demonstrated
“deficiency,” but the infants exhibited no symptoms. Their ratios returned to “normal” after
feeding linoleate or resuming “normal” formula. The values for “normal” ratios were taken
from four-month old infants consuming a formula that contained over 55 percent of its fat as
linoleate! The seventh infant had a distended abdomen and had been vomiting since birth and
had most of its small intestine surgically removed the day it was born. It was fed
intravenously for 4.5 months until it died of meningitis, and was the only infant to display
eczema. The physicians made no attempt to cure the eczema by feeding or topically applying
EFA, so there was no evidence that it resulted from EFA deficiency, but the infant’s triene-to-
tetraene ratio was 18.3. Because of the elevated ratios, Holman and his colleagues concluded
that all seven infants were EFA-deficient.

The assumption that the production of Mead acid should be maximally suppressed would
make sense if we could show that it does not belong in the body. But that is far from clear. An
oleate-to-linoleate ratio greater than ten will elevate levels of Mead acid (17) and several
traditional dietary fats provide such a ratio: butter, tallow, and lamb fat (35). Mead acid is the
predominant PUFA in the healthy cartilage tissue of young animals on EFA-sufficient diets
(55) and the placenta preferentially supplies it to the growing fetus during pregnancy: four

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 50/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

times as much is present in umbilical cord blood as in maternal circulation (52). It is therefore
possible, though far from proven, that Mead acid plays an essential role in the body. Clearly,
whichever the case is, the use of the triene-to-tetraene ratio in the EFA literature has greatly
exaggerated the requirement for these fatty acids.

8 Is EPA an Essential Fatty Acid?

Fish oils provide both DHA and another omega-3 fatty acid, eicosapentaenoic acid (EPA). The
EPA content of terrestrial animal products, even those rich in DHA, is generally minimal.
Discussions of essential fatty acids often highlight not only DHA for its role in the brain and
retina, but also EPA for its putative role in protecting against inflammation. Considerable
evidence, however, suggests that DHA is the exclusive essential omega-3 fatty acid just like
arachidonate seems to be the exclusive essential omega-6 fatty acid.

In the blood, the levels of DHA and arachidonate are tightly correlated with one another (77).
DHA and arachidonate, but not other omega-3 or omega-6 fatty acids, are selectively
transferred across the placenta (78). Whereas arachidonate is present in substantial amounts
in most tissues, DHA is found in lower amounts in them and primarily accumulates in the
retina and cerebral cortex (79) where its concentration is highly regulated and it is the
exclusive omega-3 fatty acid found (70). The DHA content in these tissues is very similar
across mammalian species, despite widely varying intakes of omega-3 fatty acids (17), strongly
suggesting it is functionally important. There are no tissues, however, that contain tightly
regulated levels of EPA.

When Holman and Widmer first demonstrated in 1949 that omega-3 and omega-6 fatty acids
represent two distinct families of PUFA (8), they examined nine different tissues in rats on
normal lab diets and could not find even a trace of EPA. DHA was the omega-3 fatty acid
found in these tissues. In rats that consumed an EFA- deficient, sucrose-casein diet for three
months and were subsequently supplemented with the omega-3 precursor fatty acid ALA,
EPA turned up in blood and kidney tissue, but not in any of the other tissues. The authors
concluded the following: “Kidney damage is one of the chief results of essential fatty acid
deficiency. The observed appearance of pentaenoic acid [EPA] in kidney and blood after
supplementation with linolenate [ALA] may [be a] result of impaired function of kidney tissue
and may possibly be an abnormal synthesis.”

Several years later Holman authored a paper with another colleague (10) showing that rats
synthesized plenty of EPA from ALA when they were fed on a diet deficient in both EFA and
vitamin B6. The ALA supplements made the EFA-deficiency dermatitis worse in the absence
of B6; when B6 was added to the diet, however, the ALA gave rise to less EPA and more DHA

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 51/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

and no longer aggravated the dermatitis. This study also showed that B6 increases the
conversion of linoleate to arachidonate, and thus strongly argued that the activity of the
enzyme delta-6 desaturase (D6D) is – whether directly or indirectly – very tightly dependent
on B6 status.

D6D is involved in the conversion of linoleate to arachdionate, ALA to EPA, and EPA to DHA
(72). Even in healthy people without any genetic decreases in D6D activity, an excess of
linoleate would suppress the conversion of EPA to DHA. Linoleate would not only compete
for the enzyme activity and win out because of its greater abundance – but like all PUFA it
would suppress the production of the enzyme itself (48).

Studies supplementing humans with ALA labeled with a radioactive tracer have suggested
that EPA rather than DHA is the major product (72). These studies suffer from several flaws:
they are conducted in humans consuming a massive excess of linoleate; they have mostly used
very small amounts of ALA; they measure blood levels instead of tissue levels; and they do not
take into account vitamin B6 status or any of the other variables that affect desaturase activity
(see main text in the The EFA Requirement is Affected by Other Nutrients section). The
standard American diet is six to seven percent PUFA (17), which is at least 15 times the
required amount, and most of it is linoleate from vegetable oil. As argued above, the linoleate
would depress the production of DHA, especially if the dose of ALA is small and therefore
less effective at competing for the enzymes. Most of these studies have used doses between 40
milligrams and one gram per day and shown only trace production of DHA and between five-
fold and 100-fold greater production of EPA. The one study that used 3.5 grams per day,
however, showed that 3.8 percent of it was converted to DHA and less than twice as much was
converted to EPA. Since DHA but not EPA is preferentially incorporated into tissues,
measuring blood levels probably overestimates EPA and underestimates DHA. Finally, diets
rich in biotin, calcium, and B6, and low in rancid oils and total PUFA would maximize the
conversion of ALA and EPA to DHA.

Much has been made of EPA’s putative “anti-inflammatory” role, but this effect seems to be
more of an interference with the metabolism of the essential arachdionate than the
performance of any essential role itself. Tissues use arachidonate to synthesize inflammatory
prostaglandins and related molecules during the acute phase of inflammation and anti-
inflammatory compounds during the resolution phase. Because it is a PUFA with the same
number of carbon atoms, EPA competes with arachidonate for all of the enzymes that
metabolize it. The prostaglandins made from EPA are generally weak or inert, and thus less
inflammatory. It makes little sense, however, that the body would require an essential
compound just to make other compounds that do nothing. DHA, by contrast, is used to

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 52/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

synthesize active anti-inflammatory mediators that participate in the resolution phase of

inflammation. EPA only makes such compounds in the presence of aspirin (40). EPA is thus
likely to simply be a byproduct of compromised DHA synthesis.

9 Figure 3. PUFAs Are Easily Oxidized

Corners and ends of lines represent carbon atoms; hydrogen atoms extend outside the chain
from the carbon atoms but are not shown; lines represent chemical bonds and double lines
represent double bonds. Single dots represent unpaired electrons.

a. Compounds with unpaired electrons, called free radicals, are capable of stealing electrons
from, or oxidizing, PUFAs. In the figure, a lipid peroxyl radical (LOO•) abstracts an electron
and a hydrogen atom from a PUFA. The most vulnerable carbon is that which is single-
bonded to two other carbon atoms that are each engaging in a double bond. Its leftover
electron can move left or right, toward another double bond. When double bonds are close to
one another, their electrons interact and they become more stable. The carbon that the
original double bond moved away from, however, becomes vulnerable to peroxidation.

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 53/54
11/28/22, 9:13 PM How Essential Are the Essential Fatty Acids?

b. The addition of a hydrogen to a lipid peroxyl radical forms a lipid peroxide; the addition of
oxygen to an oxidized fatty acid forms a lipid peroxyl radical that can oxidize another fatty
acid (LH).

c. There are now two lipid peroxides, one shown in its chemical structure and one as the
abbreviation LOOH. The newly oxidized fatty acid (L•) can peroxidze and repeat the cycle.

d. Malondialdehyde. Formed during the degradation of lipid peroxides.

Comments

Write a comment…

© 2022 Chris Masterjohn, PhD ∙ Privacy ∙ Terms ∙ Collection notice

Substack is the home for great writing

https://chrismasterjohnphd.substack.com/p/how-essential-are-the-essential-fatty-9bd?utm_source=substack&utm_medium=email 54/54