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THE PALEO DIET
THE
INSIDER
Vol. 2, Issue 4
GOUT AND DIET
MYTHS AND
TRUTHS ABOUT
GOUT
WILD SALMON
DELIGHT RECIPE
HEALTHY
HABITS OVER
MEDICATION
LOREN CORDAIN,
PH.D.
1
Vol. 2 ◆ Issue 4
GOUT AND DIET
about gout – intense pain and swelling of the big toe
joint.
Most of our readers are well aware of the metabolic
syndrome and the five classic diseases comprising it :
1) high blood pressure, 2) type 2 diabetes, 3) coronary
heart disease, 4) obesity, and 5) dyslipidemia [increased
blood triglycerides, increased small dense LDL
cholesterol and decreased HDL cholesterol].1
Gout is one of humanity’s oldest diseases on written
record, having been identified by the Egyptians in
2640 BC and recognized by Hippocrates in the 5th
century BC.
Originally, gout was associated with the wealthy
and affluent, such that it has been called a “disease of
kings and king of diseases.”3 Throughout recorded
history, gout has rubbed shoulders with the rich
and famous, affecting kings (Alexander the Great,
Charlemagne, Henry VIII), statesmen (Benjamin
Franklin, Alexander Hamilton), artists (Alfred Lord
Tennyson and Voltaire), and scientists (Isaac Newton,
Charles Darwin, Leonardo da Vinci.)4 Historically,
the association of gout with wealth and affluence had
been attributed to gluttony and excess consumption of
alcohol. As is the case with many diet related diseases,
there is intriguing information suggesting that gout
was either unknown or rare in indigenous peoples,58
and as they adopted western diets, the incidence of
gout rapidly increased.9,10 Gout is no longer considered
to be a disease of the wealthy and affluent but rather
now is a worldwide disease associated with the
adoption of western diets.3,11 In the U.S. gout afflicts at
least 3.4 million men.12
Figure 1. “The Gout” by James Gillray, 1799, London
An additional disease that frequently occurs in patients
with the metabolic syndrome is gout.1 Consequently
it is sometimes considered to be a disease of insulin
resistance that is part of the metabolic syndrome.2
In this issue I will show you why gout often occurs
simultaneously with the classic diseases of insulin
resistance. More importantly, I will show you how and
why current dietary recommendations to treat gout are
largely ineffective and that a better nutritional strategy
exists to ameliorate or prevent disease symptoms.
This dietary strategy is supported not only by recent
empirical data, but also by a long trail of evolutionary
and genetic evidence which demonstrates how our
genome has effectively skirted gout via certain
mutations in the face of a high meat diet.
GOUT: THE BASICS
Gout is a painful disease that can occur in any joint
or tissue throughout the body but most frequently
presents itself in the first metatarsal phalangeal joint
of the big toe or in the ankle or knee (see Figure 3).
When blood concentrations of uric acid rise too high
(>7.0 mg/dl in men and >6.0 mg/dl in women) crystals
of uric acid (monosodium urate) may form and settle in
the joint spaces causing pain, swelling, inflammation
Figure 1 pretty much sums up what most people know
2
a few other tissues within the body. The liver receives
purines from two sources: 1) the diet, and 2) the daily
breakdown of the body’s own tissues. About 2/3 of
the daily purine load comes from the body’s turnover
of cells, while 1/3 comes from the diet (11). When the
combined purine load (from both diet and turnover
of the body’s own cells) exceeds the kidney’s ability
to excrete it, blood concentrations of uric acid rise,
thereby increasing the risk for gout.
Figure 3. Gout symptoms in the first metatarsal
joint of the big toe.
The prevailing notion has been that reduction of
dietary sources of purines, particularly from meats
and seafood could help to ameliorate and prevent
gout symptoms (3, 11, 13, 14). Table 1 lists the
purine concentrations of various foods and their
recommended intake for gout patients. Note that
suggested low purine foods include white bread,
crackers, sugars, sweets, cake, cookies, rice, cereals,
ice cream and milk. As you will soon see, these very
same low purine foods may not prevent gout, but may
actually represent one of its primary causes.
and stiffness (11). Continued accumulation of uric acid
crystals in a joint forms a large deposit called a tophus
which can then erode and damage nearby bones.
Hence, the proximate (nearby or immediate) cause
of gout is elevated blood concentrations of uric acid
(hyperuricemia). This information has been known
since 1859 with the publication of Alfred Garrod’s
book, “The Nature and Treatment of Gout and
Rheumatic Gout” (4). Of more interest to you, our
readers, is not necessarily the proximate cause of gout,
but rather its ultimate cause. Blood concentrations of
uric acid are a lot like a bank account – your account
balance is determined by the difference between the
amount of money you deposit and the amount you
spend. Similarly blood concentrations of uric acid
depend upon the difference between the uric acid
entering the blood and uric acid leaving the blood. The
amount of uric acid entering the blood is determined
by how much uric acid is synthesized by the liver and
then dumped into the bloodstream. The amount of
uric acid leaving the bloodstream is determined by
the rate the kidneys excrete it and to a lesser extent by
its breakdown by gut bacteria. In more than 90 % of
all gout patients, the disease results because they are
“underexcretors” – meaning that the kidney can’t get
rid of blood uric acid fast enough relative to how much
is being produced in the liver (11).
Further, the recommendation to reduce high purine
foods such as fish, shellfish, meats, poultry and organ
meats may be of dubious therapeutic value (11) because
clinical trials of low purine diets only marginally
reduce (1-2 mg/ dl) blood uric acid concentrations (1517). Although high protein, meat based diets contain
high amounts of purines and would be expected to
promote gout symptoms, protein ingestion actually
decreases blood uric acid levels by increasing uric acid
excretion (18). This seemingly paradoxical effect occurs
because the kidney increases its excretion of uric acid
when faced with elevated dietary purines (19).
So, let’s put 2 and 2 together. If high protein, meat
based diets actually increase uric acid excretion, and 90
% of all gout patients have the disease because they are
underexcretors, it makes little sense to implicate meat
and high protein diets as a fundamental causes of gout.
What we really need to look for are dietary factors
which can simultaneously increase uric acid synthesis
in the liver and suppress its secretion by the kidneys –
Bingo! What might this holy grail of a food look like?
For starters – how about the mainstays of the western
diet – maybe refined grains and refined sugars? In the
typical western diet, these foods comprise nearly 40 %
of the daily energy (20).
Let’s first talk about uric acid entering the blood. Uric
acid is synthesized in the liver and then enters the
blood, but a key element in understanding how gout
develops is knowing precisely how the liver makes uric
acid. The liver synthesizes uric acid from precursor
molecules called purines (GMP and AMP). Purines are
the nitrogenous base pairs which form the structural
cross rung molecules of both DNA and RNA. As DNA
and RNA are broken down within cells, the purines
then can be metabolized into uric acid by the liver and
3
Vol. 2 ◆ Issue 4
GOUT: THE REAL DIETARY CAUSES
It has been known for almost 40 years that fructose
ingestion or infusions result in hyperuricemia
(elevated blood uric acid levels.)21-24 However, this
information has seemingly been buried in the
medical literature, since clinical nutrition texts make
few or no dietary recommendations for gout patients
to reduce dietary sources of fructose. Fructose
stimulates synthesis of AMP and GMP which are
ultimately converted to uric acid by the liver, thereby
elevating plasma uric acid levels.24,25 Only fructose
causes this effect, as experimental 3,000 kcal day
diets consisting entirely of glucose in obese patients
did not increase plasma uric acid levels, whereas a
high sucrose (table sugar) diet did.26 Because sucrose
is composed of the two simple sugars, glucose and
fructose, then the digestion of sucrose in the gut to
its two component sugars shows that fructose alone
is responsible for inducing hyperuricemia.
In the US diet the two primary sources of fructose
Figure 5. Annual per capita consumption of
refined sugars in the U.S 1970-2000.1
Sucrose
160
140
120
100
80
60
40
20
0
121
19
102
1970
are from the digestion of sucrose and from foods containing
high fructose corn syrup. Figure 5 shows the total
consumption of all refined sugars in the U.S. from 1970
to 2000. Note that total fructose consumption (from both
the metabolism of sucrose and high fructose corn syrup)
has increased from 51.5 lbs in 1970 to 64.9 lbs in 2000 – an
increase of 26%.
Fructose causes hyperuricemia by lowering the inorganic
phosphate (Pi) content of the liver. High levels of Pi in the
liver normally slow the metabolism of GMP and AMP
into uric acid. Fructose is an unusual sugar in that it enters
liver metabolism (glycolysis) after the PFK regulatory step,
thereby causing unregulated phosphorylation of fructose to
fructose 1-P which in turn lowers both liver ATP and Pi27
Further, because fructose bypasses the PFK regulatory step,
it increases blood lactic acid which is an inhibitor of uric acid
excretion by the kidneys.28 Consequently, fructose ingestion
either from high fructose corn syrup or from sucrose
enhances uric acid production and also slows it excretion.
To add insult to injury, long term ingestion of table sugar
(sucrose) and high fructose corn syrup, because they are
high glycemic load carbohydrates, will chronically elevate
blood insulin concentrations and frequently result in insulin
High Fructose Corn Syrup
136
122
20
19
22
50
82
1980
4
Glucose
151
22
64
64
66
1990
2000
Table 1. Dietary recommendations for gout.
Gout Dietary Recommendations (2006)
3,11,13-19
Group 1: High Purine Content Foods (100-1,000 mg of Purine Nitrogen per 100g of Food)
Foods in this group should be omitted from the diet of patients who have gout (acute and remission stages)
Anchovies, Bouillon, Brains,
Broth, Consommé, Goose, Gravy
Heart, Herring, Kidney, Mackerel,
Meat Extracts, Mincemeat, Mussels
Partidge, Roe, Sardines, Scallops,
Sweetbreads, Yeast (supplement)
Group 2: Moderate Purine Content Foods
(9-100 mg of Purine Nitrogen per 100g of Food)
One serving (2-3 oz.) of meat, fish, or fowl or 1 serving (1/2 cup) of vegetables from this group is allowed
daily (depending on condition) during remissions.
Vegetables: Asparagus, Peas, Beans, Lentils,
Mushrooms, Spinach
Meat and Fish, except those listed in Group 1: Fish,
Poultry, Meat, Shellfish
Group 3: Negligible Purine Content
Foods included in this group may be used daily.
*Recommended in moderation due to fat content
Bread, white and crackers
Butter or margarine*
Cake and Cookies
Carbonated beverages
Cereal beverage (e.g., Postum)
Cereals and Cereal products
Cheese, Chocolate, Coffee,
Condiments, Cornbread,
Cream*, Custard
Eggs, Fats*, Vegetables (except
those in group 2)
Fruit, Gelatin Desserts
Herbs, Ice Cream, Milk
Macaroni noodles, Noodles
Nuts, Oil
resistance.1 Numerous studies conclusively show that
insulin is a potent inhibitor or uric acid excretion by
the kidneys.29-31 Taken together, these basic and well
established biochemical facts indicate that sucrose,
high fructose corn syrup and all high glycemic load
carbohydrates play a central role in causing gout.
Diseases of hyperuricemia are tightly coupled with
metabolic syndrome diseases because both categories
of diseases result, in part, from chronically elevated
insulin.
There is one final dietary key which completes the
picture. In addition to fructose, sucrose and high
glycemic load carbohydrates, excessive consumption
of alcoholic beverages may also promote gout
symptoms by simultaneously increasing uric acid
production and slowing its excretion. The metabolism
of alcohol (ethanol) like that of fructose reduces the
liver stores of ATP and Pi by uncoupling oxidation
from phosphorylation and thereby increases uric
acid synthesis from AMP and GMP.32 A by product
of alcohol metabolism is lactic acid which once
again inhibits uric acid excretion in the kidneys by
competitively inhibiting uric acid secretion in the
proximal tubules.11
Olives, Pickles, Popcorn
Puddings, Relishes,
Rennet Desserts, Rice
Salt, Sugar and Sweets
Tea, Vinegar, White Sauce
As you Paleo Diet Newsletter readers are well aware,
whenever a complex diet/disease question arises, insight
into the problem can almost always be gained by framing
the question in an evolutionary perspective. In the case
of gout, the recommendation to limit high purine meats
is completely contrary to the anthropological evidence
showing that animal food was the staple of hunter
gatherer diets, typically comprising more than 50% of
total daily energy.33,34 In ancestral hominins, animal food
based diets have an ancient origin dating back at least
2.5 million years, as evidenced by stone tool cut marks
present on fossilized bones of prey animals. We can also
infer that animal food was the staple of Homo erectus
living 1.77 million years ago in what is now the Dmanisi
archeological site36 in the Republic of Georgia. Because
of the seasonal scarcity or absence of plant foods at 40
degrees North latitude, these ancestral hominins almost
certainly were highly dependent upon animal foods for
many months during the year (Figure 7.)
Given our ancient heritage of meat based diets, it is
paradoxical that high purine meats would still cause
a crippling disease after more than 2 million years of
evolutionary experience. A more likely evolutionary
scenario would be that natural selection must have been
operative in selecting genes to overcome any deleterious
5
Vol. 2 ◆ Issue 4
effects of excessive dietary purine. Let’s take a look at the
evidence.
Almost all animals except humans don’t ever get gout
because they have an enzyme called uricase which converts
uric acid into a substance called allantoin, which is 5-10
times more soluble than uric acid and thus more easily
eliminated by the kidneys.11 Modern humans and great
apes cannot synthesize uricase because, over the course of
evolution, they have experienced mutations which have
inactivated the uricase gene. Chimps and other great apes
maintain much higher blood uric acid levels than do other
animals capable of synthesizing uricase, however chimps and
other great apes apparently do not ever develop gout in the
wild, presumably because they consume a near vegetarian
diet without additional purines from meat.11
As early hominins began to increasingly include more and
more purine containing animal foods into their diets,37 blood
concentration of uric acid almost certainly must have been
higher than their more vegetarian predecessors, thereby
increasing the incidence of gout. Because gout impairs
mobility, mortality must have increased in individuals
susceptible to gout. Hence, natural selection would
have rapidly weeded out individuals who were most
susceptible to gout and selected for those who could
tolerate a high meat diet without developing gout
symptoms. In support of this evolutionary scenario is a
metabolic adaptation present in humans which lowers
uric acid synthesis despite a high dietary purine intake.
Taking a look at the science of it one more time: as
the purine precursors, GMP and AMP, are ultimately
converted to uric acid there are a couple of key
intermediary steps along the way. AMP is converted
to hypoxanthine and then to xanthine and finally to
uric acid. GMP is converted to xanthine and then to
uric acid. Both the conversion of hypoxanthine to
xanthine and xanthine to uric acid are regulated by an
enzyme called xanthine oxidase. Humans avoid the
overproduction of uric acid in the face of increasing
Figure 7. The earliest evidence of fossilized hominins living outside of Africa at the Dmanisi
archaeological site in the Republic of Georgia.
6
acid concentrations dietary purine intake from meats
by decreasing the activity of xanthine oxidase.38
Compared to other animals, xanthine oxidase activity
is almost 100 times lower in humans.39
This evolutionary adaptation has occurred because the
gene coding for xanthine oxidase (more specifically
xanthine oxidoreductase) has been repressed.40
So there you have it. The evolutionary model originally
predicted that a meat based diet should not increase
the risk for gout. Now we have genetic and biochemical
evidence supporting the evolutionary model. The final
corroborative link would be experimental evidence.
If you put gout patients on a meat based, high protein
diet, reduce refined sugars and high glycemic load
carbohydrates, what do you think will happen.
program normalized serum uric acid concentrations in
7 of 12 gout patients and significantly decreased gout
attacks. The authors concluded their paper by saying
“Current dietary recommendations for gout may need
re-evaluation”.
EPILOGUE:
Six years have now come and gone since this
revolutionary clinical trial has been conducted. You
might think that the rheumatology community would
jump onto this band wagon as fast as a hot knife through
butter. Ah, we should be so lucky – not in our wildest
dreams. There has not been a single corroborative or
follow up study, and the misconception that a high
purine, meat based diet causes gout continues to be
spread in prestigious world wide medical journals.13
What might the evolutionary paradigm predict? Let’s
take a look.
THE PROOF IS IN THE PUDDING
(A CLINICAL TRIAL)
As is the case with many diet related diseases, the
dogma has been so well established that it is difficult
to unlearn what was once known to be the absolute
truth. Nothing could be a better example of this lesson
than the dietary dogma for treating gout. It took
until the year 2000 before anyone ever tried putting
gout patients on a high protein, low glycemic load
diet to see what would happen.41 Low and behold this
7
Vol. 2 ◆ Issue 4
PRIMAL IN THE KITCHEN
Prepare a large saucepan with a steamer basket
and 1 inch of water. Bring to a boil. Reduce heat
to simmer, place salmon in steamer and cook for
fifteen minutes.
WILD SALMON DELIGHT
Heat oil in a cast iron skillet over medium
flame. Add dill, paprika, pepper, and
mushrooms and sauté for five minutes. Remove
from heat.
2 wild salmon filets, 4-6 oz. ea
1 Tb. extra virgin olive oil
1 t. fresh dill, finely chopped
1 t. ground paprika
1/2 t. freshly ground black pepper
4 oz. white mushrooms, sliced
1 large red tomato, diced
Once salmon has finished cooking, remove
from pan and top with mushroom and tomato
mixture.
Copyright ©2011. The Paleo Diet Cookbook. All Rights Reserved.
8
SUCCESS STORY
Hi Loren,
Thanks for your personal response.Your contribution
to the ongoing dialog about human nutrition, by so
powerfully advancing the scientific arguments in favor
of The Paleo diet, is very much appreciated. Your
writing has had a profound influence on what I eat
everyday, and what I teach to others about nutrition. A
number of my patients have made life altering changes
in their nutritional patterns because of your writings.
Each of them has obtained a copy of one or more of
your books. To be sure, I have learned from other
nutritionists, but your influence has been the most
important because of your lucid articulation of the
over-arching theory of the hunter-gatherer diet.
For my own story, I trained and was boarded in
General Surgery in the late ‘70s, and then spent a very
satisfying twenty plus year career as an emergency
physician, a specialty in which I was also boarded. I
worked in a big urban hospital emergency department,
which included nine years of administration as
Assistant Chief and then Chief. I loved the medical
practice, but I was caring for others while neglecting
myself. I was hypertensive (consistently BP of 144/88),
overweight (body fat 34%, BMI 28.7), with abnormal
cholesterol (180-190) , and a resting pulse in the low
70s. My HDLs were low.
At age 55 I retired, moved to a tiny community in
the Sierra mountains with my family, and decided to pay
attention to my own health, by actively studying human
nutrition and weight loss strategies. I had had a two
decade history of yoyo’ing weight, by what I call now
the “starvation diet”, trying to eat less of the same calorie
dense, high glycemic index processed salty stuff. I thought
it was “healthy” food. But I have since learned otherwise; it
was in fact endocrinologically poisonous. This starvation
diet spells doom for millions of otherwise well intended
Americans who know they need to lose weight, and are
trying desperately to do so, but are trapped by their own
unfortunate and unintended nutritional ignorance.
I read voluminously, including all the major diet books
cover to cover Atkins, South Beach, Weil, Ornish, BrandMiller, Willets, McDougal, Pritikin, and others. I went
back and reviewed the basic biochemistry of lipid, protein,
and carbohydrate metabolism. My wife invited me to
join her at Weight Watchers, and I started counting all
my “points”. I was counting points and losing weight, but
ravenously hungry all the time... the starvation diet at
9
Vol. 2 ◆ Issue 4
work. I realized that counting points was not enough.
I realized I could not be hungry all the time for the
rest of my life. Two scientific nutritional concepts
turned out to be cornerstones in my “cracking” the
weight loss nut.
The first was the fundamental importance of
glycemic index, and the effect this has on insulin and
glucagon levels and resultant wild swings in blood
sugar and hunger levels. The second was calorie
density: the fact that we eat to satiety based on volume
of food eaten, not number of calories. Since only
vegetables, and some fruits, are low calorie density
foods, each meal must include a generous portion of
these food categories.
But the real breakthrough happened when a fellow
emergency physician, a colleague and friend, told
me of a radio talk show he heard in which Dr.
Eaton was interviewed. Knowing of my interest in
nutrition, he strongly suggested I look into the paleo
approach to nutrition. Further, he said that Dr. Eaton
recommended reading the book The Paleo Diet and
the articles available online at Dr. Loren Cordain’s
website. Reading your book, I quickly realized that all
of the apparently disparate concepts I was learning
about healthful nutrition fell neatly and logically into
place under the overarching theory that the most
healthful diet is the one we humans evolved eating.
Suddenly calorie density and low glycemic index made
sense, because those were the only foods available
to us as we evolved. The dramatic diminution of
mortality in the prospective, blinded fish oil study
on post-myocardial infarction patients made sense
once we realize the omega 3/6 ratio of our ancestors
and the availability of animal based omega 3 in the
wild meat and seafood they ate. In fact, all kinds of
apparently disparate nutritional learnings make sense
when they are looked at in the light of the theory of
evolutionary nutrition. That’s the learning I got directly
from you, and I thank you for it.
For my own testimonial, I have gone from a body
fat of 34% to 7%, a BMI of 28.7 to 20.6, an abnormal
blood pressure of 144/88 to a consistent 104/62 and a
high cholesterol of 190 to 132. My HDLs are up. My
triglycerides are 35. My resting pulse is now in the high
40s. For the three years before I started eating “paleo”, I
had been taking 300 mg of Zantac for G.E.R.D. virtually
every single night. In the past two years, I believe I have
taken four doses total, and that was always in the context
of dietary “indiscretion”. I had been experiencing about
five years of D.J.D. inflammation in several of the P.I.P.
joints of my fingers with resultant swelling. That has
completely quieted down.
The three way combination of eating huntergatherer
food, getting my BMI down under 21, and exercising
is incredibly healing and powerful medicine; and it
beats hands down the medications we give our patients,
like anti-hypertensives, lipid lowering agents, and
hypoglycemic drugs. Those may provide some benefit
for individuals who are unable to change their diet
and weight, but they have no effect on the overall root
cultural problems of diet, obesity, and sedentary life-style
that is endemic in our Western society.
Thanks again for your powerful contribution to my
understanding of human nutrition. I’d be happy to post
an endorsement to your website. I’ll do the posting with
my first name only for privacy purposes.
Warm regards,
Steve L., MD
10
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11
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