I copyed this from Raypeat.com..... Since
the first doctor noticed, hundreds of years ago, that the urine of a
diabetic patient tasted sweet, it has been common to call the condition
the sugar disease, or sugar diabetes, and since nothing was
known about physiological chemistry, it was commonly believed that
eating too much sugar had to be the cause, since the ability of the body
to convert the protein in tissues into sugar wasn’t discovered until
1848, by Claude Bernard (who realized that diabetics lost more sugar
than they took in). Even though patients continued to pass sugar in
their urine until they died, despite the elimination of sugar from their
diet, medical policy required that they be restrained to keep them from
eating sugar. That prescientific medical belief, that eating sugar
causes diabetes, is still held by a very large number, probably the
majority, of physicians.
Originally,
diabetes was understood to be a wasting disease, but as
it became common for doctors to measure glucose, obese people were often
found to have hyperglycemia, so the name diabetes has been extended to
them, as type 2 diabetes. High blood sugar is often seen along with high
blood pressure and obesity in Cushing's syndrome, with excess cortisol,
and these features are also used to define the newer metabolic
syndrome.
Following
the old reasoning about the sugar disease, the newer kind of obese
diabetes is commonly blamed on eating too much sugar. Obesity,
especially a fat waist, and all its associated health problems, are said
by some doctors to be the result of eating too much sugar, especially
fructose. (Starch is the only common carbohydrate that contains
no fructose.) Obesity is associated not only with diabetes or insulin
resistance, but also with atheroslcerosis and heart disease, high blood
pressure, generalized inflammation, arthritis, depression, risk of
dementia, and cancer.
There
is general agreement about the problems commonly associated with
obesity, but not about the causes or the way to prevent or cure obesity
and the associated conditions.
In
an earlier newsletter, I wrote about P. A. Piorry in Paris, in 1864,
and Dr. William Budd in England, in 1867,
who treated diabetes by adding a large amount of ordinary sugar,
sucrose, to the patient's diet. Glucose was known to be the sugar
appearing in the diabetics' urine, but sucrose consists of half glucose,
and half fructose. In 1874, E. Kulz in Germany reported that diabetics
could assimilate fructose better than glucose. In the next decades there
were several more reports on the benefits of feeding fructose,
including the reduction of glucose in the urine. With the discovery of
insulin in 1922, fructose therapy was practically forgotten, until the
1950s when new manufacturing techniques began to make it economical to
use.
Its use in diabetic diets became so popular that it became available in health food
stores, and was also used in hospitals for intravenous feeding.
However,
while fructose was becoming popular, the cholesterol theory of heart
disease was being promoted. This was the theory that eating foods
containing saturated fat and cholesterol caused heart disease. (My
newsletter, Cholesterol, longevity, intelligence, and health, discussed
the development of that theory.)
A
Swedish physician and researcher, Uffe Ravnskov, has reviewed the
medical arguments for the theory that lipids in the blood are the
cause of atherosclerosis and heart disease, and shows that there has
never been evidence of causality, something which some people, such as
Broda Barnes, understood from the beginning. In the 1950s, an English
professor, John Yudkin, didn't accept the idea that eating saturated fat
was the cause of high blood levels of triglycerides and cholesterol,
but he didn’t question the theory that lipids in the blood caused the
circulatory disease. He argued that it was sugar, especially the
fructose component of sucrose, rather than dietary fat, that caused the
high blood lipids seen in the affluent countries, and consequently the
diseases. He was sure it was a specific chemical effect of the fructose,
because he argued that the nutrients that were removed in refining
white flour and white sugar were insignificant, in the whole diet.
Following
the publication of Yudkin's books, and coinciding with increasing
promotion of the health benefits of unsaturated vegetable oils, many
people were converted to Yudkin's version of the lipid theory of heart
disease, i.e., that the "bad lipids" in the blood are the result of
eating sugar. This has grown into essentially a cult, in which sugar is
believed to act like an intoxicant, forcing people to eat until they
become obese, and develop the "metabolic syndrome," and "diabetes," and
the many problems that derive from that.
The
publicity campaign against
"saturated fat" as an ally of cholesterol derived its support from the
commercial promotion of the polyunsaturated seed oils as food for
humans. Although the early investigators of vitamin E knew that the
polyunsaturated oils could cause sterility, and others later found that
their use in commercial animal foods could cause brain degeneration,
there were a few biologists (mostly associated with George Burr) who
believed that this type of fatty acid is an essential nutrient.
George
and Mildred Burr had created what they claimed to be a disease in rats
caused by the absence of linoleic or linolenic acid in their food.
Although well known researchers had previously published evidence that
animals on a fat
free diet were healthy--even healthier than on a normal diet--Burr and
his wife published their contradictory claim without bothering to
discuss the conflicting evidence. I haven't seen any instance in which
Burr or his followers ever mentioned the conflicting evidence. Although
other biologists didn't accept Burr's claims, and several researchers
subsequently published contrary results, he later became famous when the
seed oil industry wanted scientific-seeming reasons for selling their
product as an "essential" food. The fact that eating the polyunsaturated
fats could cause the blood cholesterol level to decrease slightly was
advertised as a health benefit. Later, when human trials showed that
more people on the "heart healthy" diet died of heart disease and
cancer, more conventional means of advertising were used instead of
human tests.
Burr's
experimental diet consisted of purified casein (milk protein) and
purified sucrose, supplemented with a vitamin concentrate and some
minerals. Several of the B vitamins weren't known at the time, and the
mineral mixture lacked zinc, copper, manganese, molybdenum, and
selenium. More of the essential nutrients were unknown in his time than
in Yudkin's, so his failure to consider the possibility of other
nutritional deficiencies affecting health is more understandable.
In
1933, Burr observed that his fat-deficient rats consumed oxygen at an
extremely high rate,
and even then, the thought didn't occur to him that other nutritional
deficiencies might have been involved in the condition he described.
Ordinarily, the need for vitamins and minerals corresponds to the rate
at which calories are being burned, the metabolic rate. Burr recalled
that the rats on the fat free diet drank more water, and he reasoned
that the absence of linoleic or linolenic acid in their skin was
allowing water vapor to escape at a high rate. He didn't explain why the
saturated fats the rats were synthesizing from sugar didn't serve at
least as well as a "vapor barrier"; they are more effective at
water-proofing than unsaturated fats, because of their greater
hydrophobicity. The condensed and cross-linked keratin protein in skin
cells is the main reason for the skin's relatively low permeability.
When an animal is burning calories at a higher rate, its sweat glands
are more actively maintaining
a normal body temperature, cooling by evaporation; the amount of water
evaporated is an approximate measure of metabolic rate, and of thyroid
function.
In
1936, a man in Burr's lab, William Brown, agreed to eat a similar diet
for six months, to see whether the "essential fatty acid deficiency"
affected humans as it did rats.
The
diet was very similar to the rats', with a large part of the daily 2500
calories being provided at hourly intervals during the day by sugar
syrup (flavored with citric acid and anise oil),
protein from 4 quarts of special fat-free skimmed milk, a quart of which
was made into cottage cheese, the juice of half an orange, and a
"biscuit" made with potato starch, baking powder, mineral oil, and salt,
with iron, viosterol (vitamin D), and carotene supplemented.
Brown
had suffered from weekly migraine headaches since childhood, and his
blood pressure was a little high when he began the diet. After six weeks
on the diet, his migraines stopped, and never returned. His plasma
inorganic phosphorus declined slightly during the experiment (3.43
mg./100 cc. of plasma and 2.64 on the diet, and after six months on a
normal diet 4.2 mg.%), and his total serum proteins increased from 6.98
gm.% to 8.06 gm.%
on the experimental diet. His leucocyte count was lower on the high
sugar diet, but he didn't experience colds or other sickness. On a
normal diet, his systolic blood pressure varied from 140 to 150 mm. of
mercury, the diastolic, 95 to 100. After a few months on the sugar and
milk diet, his blood pressure had lowered to about 130 over 85 to 88.
Several months after he returned to a normal diet, his blood pressure
rose to the previous level.
On
a normal diet, his weight was 152 pounds, and his metabolic rate was
from 9% to 12% below normal, but after six months on the diet it had
increased to 2% below normal. After three months on the sugar and milk
diet, his weight leveled off at 138 pounds. After being on the
diet, when he ate 2000 calories of sugar and milk within two hours, his
respiratory quotient would exceed 1.0, but on his normal diet his
maximum respiratory quotient following those foods was less than 1.0.
The
effect of diabetes is to keep the respiratory quotient low, since a
respiratory quotient of one corresponds to the oxidation of pure
carbohydrate, and extreme diabetics oxidize fat in preference to
carbohydrate, and may have a quotient just a little above 0.7. The
results of Brown's and Burr's experiments could be interpreted to mean
that the polyunsaturated fats not only lower the metabolic rate, but
especially interfere with the metabolism of sugars. In other words, they
suggest that the normal diet
is diabetogenic.
During
the six months of the experiment, the unsaturation of Brown's serum
lipids decreased. The authors reported that "There was no essential
change in the serum cholesterol as a result of the change in diet."
However, in November and December, two months before the experiment
began, it had been 252 mg.% in two measurements. At the beginning of the
test, it was 298, two weeks later, 228, and four months later, 206 mg%.
The total quantity of lipids in his blood didn't seem to change much,
since the triglycerides increased as the cholesterol decreased.
By
the time of Brown's experiment, other researchers had demonstrated that
the cholesterol level was increased in hypothyroidism, and decreased as
thyroid function, and oxygen consumption, increased. If Burr's team had
been reading the medical literature, they would have understood the
relation between Brown's increased metabolic rate and decreased
cholesterol level. But they did record the facts, which is valuable.
The
authors wrote that "The most interesting subjective effect of the
'fat-free' regimen was the definite disappearance of a feeling of
fatigue at the end of the day's work."
A
lowered metabolic rate and energy production is a common feature of
aging and most degenerative diseases. From the beginning of an animal's
life, sugars are the primary source of energy, and with maturation and
aging there is a shift toward replacing sugar oxidation with fat
oxidation. Old people are able to metabolize fat at the same rate as
younger people, but their overall metabolic rate is lower, because they
are unable to oxidize sugar at the same high rate as young people. Fat
people have a similar selectively reduced ability to oxidize sugar.
Stress
and starvation lead to a relative reliance on the fats stored in the
tissues, and the mobilization of these as circulating free fatty acids
contributes to a slowing of metabolism and a shift away from the use of
glucose for energy. This is adaptive in the short term, since relatively
little glucose is stored in the tissues (as glycogen), and the proteins
making up the body would be rapidly consumed for energy, if it were not
for the reduced energy demands resulting from the effects of the free
fatty acids.
One
of the points at which fatty acids suppress the use of glucose is at
the point at which it is converted into fructose, in the process of
glycolysis. When fructose
is available, it can by-pass this barrier to the use of glucose, and
continue to provide pyruvic acid for continuing oxidative metabolism,
and if the mitochondria themselves aren't providing sufficient energy,
it can leave the cell as lactate, allowing continuing glycolytic energy
production. In the brain, this can sustain life in an emergency.
Many
people lately have been told, as part of a campaign to explain the high
incidence of fatty liver degeneration in the US, supposedly resulting
from eating too much sugar, that fructose can be metabolized only by the
liver. The liver does have the highest capacity for metabolizing
fructose, but the other organs do metabolize it.
If
fructose can by-pass the fatty acids' inhibition of glucose metabolism,
to be oxidized when glucose can't, and if the metabolism of diabetes
involves the oxidation of fatty acids instead of glucose, then we would
expect there to be less than the normal amount of fructose in the serum
of diabetics, although their defining trait is the presence of an
increased amount of glucose. According to Osuagwu and Madumere (2008),
that is the case. If a fructose deficiency exists in diabetes, then it
is appropriate to supplement it in the diet.
Besides
being
one of the forms of sugar involved in ordinary energy production,
interchangeable with glucose, fructose has some special functions, that
aren't as well performed by glucose. It is the main sugar involved in
reproduction, in the seminal fluid and intrauterine fluid, and in the
developing fetus. After these crucial stages of life are past, glucose
becomes the primary molecular source of energy, except when the system
is under stress. It has been suggested (Jauniaux, et al., 2005) that the
predominance of fructose rather than glucose in the embryo's
environment helps to maintain ATP and the oxidative state (cellular
redox potential) during development in the low-oxygen environment. The
placenta turns glucose from the mother's blood into fructose, and the
fructose in the mother's blood can pass through into the fetus, and
although glucose can move back from the fetus into the mother's blood,
fructose
is unable to move in that direction, so a high concentration is
maintained in the fluids around the fetus.
The
control of the redox potential is sometimes called the "redox
signalling system," since it coherently affects all processes and
conditions in the cell, including pH and hydrophobicity. For example,
when a cell prepares to divide, the balance shifts strongly away from
the oxidative condition, with increases in the ratios of NADH to NAD+,
of GSH to GSSG, and of lactate to pyruvate. These same shifts occur
during most kinds of stress.
In
natural stress, decreased availability of oxygen or nutrients is often
the key problem, and many poisons can produce similar interference with
energy production, for example cyanide or carbon monoxide, which block
the use of oxygen, or ethanol, which inhibits the oxidation of sugars,
fats, and amino acids (Shelmet, et al., 1988).
When
oxygen isn't constantly removing electrons from cells (being chemically
reduced by them) those electrons will react elsewhere, creating free
radicals (including activated oxygen) and reduced iron, that will create
inappropriate chemical reactions (Niknahad, et al., 1995; MacAllister,
et al., 2011).
Stresses
and poisons of many different types, interfering with the normal flow
of electrons to oxygen, produce large amounts of free radicals, which
can spread structural and chemical damage, involving all systems of the
cell. Ethyl alcohol is a common potentially toxic substance that can
have this effect, causing oxidative damage by allowing an excess of
electrons to accumulate in the cell, shifting the cells' balance away
from the stable oxidized state.
Fructose
has been known for many years to accelerate the oxidation of ethanol
(by about 80%).
Oxygen consumption in the presence of ethanol is increased by fructose
more than by glucose (Thieden and Lundquist, 1967). Besides removing the
alcohol from the body more quickly, it prevents the oxidative damage,
by maintaining or restoring the cell's redox balance, the relatively
oxidized state of the NADH/NAD+, lactate/pyruvate, and GSH/GSSH systems.
Although glucose has this stabilizing, pro-oxidative function in many
situations, this is a general feature of fructose, sometimes allowing it
to have the opposite effect of glucose on the cell's redox state. It
seems to be largely this generalized shift of the cell's redox state
towards oxidation that is behind the ability of a small amount of
fructose to catalyze the more rapid oxidation of a large amount of
glucose.
Besides
protecting against the reductive stresses, fructose can also protect
against the oxidative stress of increased hydrogen peroxide (Spasojevic,
et al., 2009). Its metabolite, fructose 1,6-bisphosphate, is even more
effective as an antioxidant.
Keeping
the metabolic rate high has many benefits, including the rapid renewal
of cells and their components, such as cholesterol and other lipids, and
proteins, which are always susceptible to damage from oxidants, but the
high metabolic rate also tends to keep the redox system in the proper
balance, reducing the rate of oxidative damage.
Endotoxin
absorbed from the intestine is one of the ubiquitous stresses that
tends to cause free radical damage. Fructose, probably more than
glucose, is protective against damage from endotoxin.
Many
stressors cause capillary leakage, allowing albumin and other blood
components to enter extracellular spaces or to be lost in the urine, and
this is a feature of diabetes, obesity, and a variety of inflammatory
and degenerative diseases including Alzheimer's disease (Szekanecz and
Koch, 2008; Ujiie, et al., 2003). Although
the mechanism isn't understood, fructose supports capillary integrity;
fructose feeding for 4 and 8 weeks caused a 56% and 51% reduction in
capillary leakage, respectively (Chakir, et al., 1998; Plante, et al.,
2003).
The
ability of the mitochondria to oxidize pyruvic acid and glucose is
characteristically lost to some degree in cancer. When this oxidation
fails, the disturbed redox balance of the cell will usually lead to the
cell's death, but if it can survive, this balance favors growth and cell
division, rather than differentiated function. This was Otto Warburg's
discovery, that was rejected by official medicine for 75 years.
Cancer
researchers have become interested in this enzyme system that controls
the oxidation of pyruvic acid (and thus sugar) by the mitochondria,
since these enzymes are crucially defective in cancer cells (and also in
diabetes). The chemical DCA, dichloroacetate, is effective against a
variety of cancers, and it acts by reactivating the enzymes that oxidize
pyruvic acid. Thyroid hormone, insulin, and fructose also activate
these enzymes. These are the enzymes that are inactivated by excessive
exposure to fatty acids, and that are involved in the progressive
replacement of sugar oxidation by fat oxidation, during stress and
aging, and in degenerative diseases; for example, a process that
inactivates the energy-producing pyruvate dehydrogenase in Alzheimer's
disease
has been identified (Ishiguro, 1998). Niacinamide, by lowering free
fatty acids and regulating the redox system, supporting sugar oxidation,
is useful in the whole spectrum of metabolic degenerative diseases.
A
few times in the last 80 years, people (starting with Nasonov) have
recognized that the hydrophobicity of a cell changes with its degree of
excitation, and with its energy level. Recently, even in non-living
physical-chemical systems, hydrophobicity and redox potential have been
seen to vary together and to influence each other. Recent work shows how
the oxidation of fatty acids contributes to the dissolution of
mitochondria (Macchioni, et al., 2010). At first glance it might seem
odd that the
presence of fatty material could reduce the "fat loving" (lipophilic,
equivalent to hydrophobic) property of a cell, but the fat used as fuel
is in the form of fatty acids, which are soap-like, and spontaneously
introduce "wetness" into the relatively water-resistant cell substance.
The presence of fatty acids, impairing the last oxidative stage of
respiration, increases the tendency of the mitochondrion to release its
cytochrome c into the cell in a reduced form, leading to the apoptotic
death of the cell. The oxidized form of the cytochrome is more
hydrophobic, and stable.
Burr
didn't understand that it was his rats' high sugar diet, freed of the
anti-oxidative unsaturated fatty acids, that caused their
extremely high metabolic rate, but since that time many experiments have
made it clear that it is specifically the fructose component of sucrose
that is protective against the antimetabolic fats.
Although
Brown, et al., weren't focusing on the biological effects of sugar,
their results are important in the history of sugar research because
their work was done before the culture had been influenced by the
development of the lipid theory of heart disease, and the later idea
that fructose is responsible for increasing the blood lipids.
In
1963 and 1964, experiments (Carroll, 1964) showed that the effects of
glucose and fructose were radically affected by the type of fat in the
diet. Although 0.6% of calories as polyunsaturated fat prevents the
appearance of the Mead acid (which is considered to indicate a
deficiency of essential fats) the "high fructose" diets consistently add
10% or more corn oil or other highly unsaturated fat to the diet. These
large quantities of PUFA aren't necessary to prevent a deficiency, but
they are needed to obscure the beneficial effects of fructose.
Many
studies have found that sucrose is less fattening than starch or
glucose, that is, that more calories can be consumed without gaining
weight. During exercise, the addition of fructose to glucose increases
the oxidation of carbohydrate by about 50% (Jentjens and Jeukendrup,
2005). In another experiment, rats were fed either sucrose or Coca-Cola
and Purina chow, and were allowed to eat as much as they wanted
(Bukowiecki, et al, 1983). They consumed 50% more calories without
gaining extra weight, relative to the standard diet. Ruzzin, et al.
(2005) observed rats given a 10.5% or 35% sucrose solution, or water,
and observed that the sucrose increased their energy consumption by
about 15% without increasing weight gain. Macor, et al. (1990) found
that glucose caused a smaller increase in metabolic rate in obese people
than in normal weight people, but that fructose increased their
metabolic rate as much as it did that of the normal weight people.
Tappy, et al. (1993) saw a similar increase in heat production in obese
people, relative to the
effect of glucose. Brundin, et al. (1993) compared the effects of
glucose and fructose in healthy people, and saw a greater oxygen
consumption with fructose, and also an increase in the temperature of
the blood, and a greater increase in carbon dioxide production.
These
metabolic effects have led several groups to recommend the use of
fructose for treating shock, the stress of surgery, or infection (e.g.,
Adolph, et al., 1995).
The
commonly recommended alternative to sugar in the diet is starch, but
many
studies show that it produces all of the effects that are commonly
ascribed to sucrose and fructose, for example hyperglycemia (Villaume,
et al., 1984) and increased weight gain. The addition of fructose to
glucose "can markedly reduce hyperglycemia during intraportal glucose
infusion by increasing net hepatic glucose uptake even when insulin
secretion is compromised" (Shiota, et al., 2005). "Fructose appears most
effective in those normal individuals who have the poorest glucose
tolerance" (Moore, et al., 2000).
Lipid
peroxidation is involved in the degenerative diseases, and many
publications argue that fructose increases it, despite the fact that it
can increase the production of uric acid, which is a
major component of our endogenous antioxidant system (e.g., Waring, et
al., 2003). When rats were fed for 8 weeks on a diet with 18% fructose
and 11% saturated fatty acids, the content of polyunsatured fats in the
blood decreased, as they had in the Brown, et al., experiment, and their
total antioxidant status was increased (Girard, et al., 2005). When
stroke-prone spontaneously hypertensive rats were given 60% fructose,
superoxide dismutase in their liver was increased, and the authors
suggest that this "may constitute an early protective mechanism"
(Brosnan and Carkner, 2008). When people were given a 300 calorie drink
containing glucose, or fructose, or orange juice, those receiving the
glucose had a large increase in oxidative and inflammatory stress
(reactive oxygen species, and NF-kappaB binding), and those changes were
absent in those receiving the fructose or orange juice (Ghanim, et al.,
2007).
One
of the observations in Brown, et al., was that the level of phosphate
in the serum decreased during the experimental diet. Several later
studies show that fructose increases the excretion of phosphate in the
urine, while decreasing the level in the serum. However, a common
opinion is that it's only the phosphorylation of fructose, increasing
the amount in cells, that causes the decrease in the serum; that could
account for the momentary drop in serum phosphate during a fructose
load, but--since there is only so much phosphate that can be bound to
intracellular fructose--it can't account for the chronic depression of
the serum phosphate on a continuing diet of fructose or sucrose.
There
are many reasons to think that a slight reduction of serum phosphate
would be beneficial. It has been suggested that eating fruit is
protective against prostate cancer, by lowering serum phosphate (Kapur,
2000). The aging suppressing gene discovered in 1997, named after the
Greek life-promoting goddess Klotho, suppresses the reabsorption of
phosphate by the kidney (which is also a function of the parathyroid
hormone), and inhibits the formation of the activated form of vitamin D,
opposing the effect of the parathyroid hormone. In the absence of the
gene, serum phosphate is high, and the animal ages and dies prematurely.
In humans, in recent years a very close association has been has been
documented between
increased phosphate levels, within the normal range, and increased risk
of cardiovascular disease. Serum phosphate is increased in people with
osteoporosis (Gallagher, et al., 1980), and various treatments that
lower serum phosphate improve bone mineralization, with the retention of
calcium phosphate (Ma and Fu, 2010; Batista, et al., 2010; Kelly, et
al., 1967; Parfitt, 1965; Kim, et al., 2003).
At
high altitude, or when taking a carbonic anhydrase inhibitor, there is
more carbon dioxide in the blood, and the serum phosphate is lower;
sucrose and fructose increase the respiratory quotient and carbon
dioxide production, and this is probably a factor in lowering the serum
phosphate.
Fructose
affects the body's ability to retain other nutrients, including
magnesium, copper, calcium, and other minerals. Comparing diets with 20%
of the calories from fructose or from cornstarch, Holbrook, et al.
(1989) concluded "The results indicate that dietary fructose enhances
mineral balance." Ordinarily, things (such as thyroid and vitamin D)
which improve the retention of magnesium and other nutrients are
considered good, but the fructose mythology allows researchers to
conclude, after finding an increased magnesium balance, with either 4%
or 20% of energy from fructose (compared to cornstarch, bread, and
rice), "that dietary fructose adversely affects macromineral homeostasis
in humans." (Milne and Nielsen, 2000).
Another
study compared the effects of a diet with plain water, or water
containing 13% glucose, or sucrose, or fructose, or high fructose corn
syrup on the properties of rats' bones: Bone mineral density and mineral
content, and bone strength, and mineral balance. The largest
differences were between animals drinking the glucose and the fructose
solutions. The rats getting the glucose had reduced phosphorus in their
bones, and more calcium in their urine, than the rats that got fructose.
"The results suggested that glucose rather than fructose exerted more
deleterious effects on mineral balance and bone" (Tsanzi, et al., 2008).
An
older experiment compared two groups with an otherwise well balanced
diet, lacking vitamin D, containing either 68% starch or 68% sucrose. A
third group got the starch diet, but with added vitamin D. The rats on
the vitamin D deficient starch diet had very low levels of calcium in
their blood, and the calcium content of their bones was low, exactly
what is expected with the vitamin D deficiency. However, the rats on the
sucrose diet, also vitamin D deficient, had normal levels of calcium in
their blood. The sucrose, unlike the starch, maintained claim
homeostasis. A radioactive calcium tracer showed normal uptake by the
bone, and also apparently normal bone development, although their bones
were lighter than those receiving vitamin D.
People
have told me that when they looked for articles on fructose in PubMed
they couldn't find anything except articles about its bad effects. There
are two reasons for that. PubMed, like the earlier Index Medicus,
represents the material in the National Library of Medicine, and is a
medical, rather than a scientific, database, and there is a large amount
of important research that it ignores. And because of the authoritarian
and conformist nature of the medical profession, when a researcher
observes something that is contrary to majority opinion, the title of
the publication is unlikely to focus on that. In too many articles in
medical journals, the title and conclusions positively misrepresent the
data reported in the article.
When
the idea of "glycemic index" was being popularized by dietitians, it
was already known that starch, consisting of chains of glucose
molecules, had a much higher index than fructose and sucrose. The more
rapid appearance of glucose in the blood stimulates more insulin, and
insulin stimulates fat synthesis, when there is more glucose than can be
oxidized immediately. If starch or glucose is eaten at the same time as
polyunsaturated fats, which inhibit its oxidation, it will produce more
fat. Many animal experiments show this, even when they are intending to
show the dangers of fructose and sucrose.
For
example (Thresher, et al., 2000), rats were fed diets with 68%
carbohydrate, 12% fat (corn oil), and 20% protein. In one group the
carbohydrate was starch (cornstarch and maltodextrin, with a glucose
equivalence of 10%), and in other groups it was either 68% sucrose, or
34% fructose and 34% glucose, or 34% fructose and 34% starch. (An
interesting oddity, fasting triglycerides were highest in the
fructose+starch group.)
The
weight of their fat pads (epididymal, retroperitoneal, and mesenteric)
was greatest in the fructose+starch group, and least in the sucrose
group. The starch group's fat
was intermediate in weight between those of the sucrose and the
fructose+glucose groups.
At
the beginning of the experimental diet, the average weight of the
animals was 213.1 grams. After five weeks, the animals in the
fructose+glucose group gained 164 grams, those in the sucrose group
gained 177 grams, and those in the starch group gained 199.2 grams. The
animals ate as much of the diet as they wanted, and those in the sucrose
group ate the least.
The
purpose of their study was to see whether fructose causes
"glucose intolerance" and "insulin resistance." Since insulin stimulates
appetite (Chance, et al, 1986; Dulloo and Girardier, 1989; Czech, 1988;
DiBattista, 1983; Sonoda, 1983; Godbole and York, 1978), and fat
synthesis, the reduced food consumption and reduced weight gain show
that fructose was protecting against these potentially harmful effects
of insulin.
Much
of the current concern about the dangers of fructose is focussed on the
cornstarch-derived high fructose corn syrup, HFCS. Many studies assume
that its composition is nearly all fructose and glucose. However,
Wahjudi, et al. (2010) analyzed samples of it before and after
hydrolyzing it in acid, to break down other carbohydrates present in it.
They
found that the carbohydrate content was several times higher than the
listed values. "The underestimation of carbohydrate content in beverages
may be a contributing factor in the development of obesity in
children," and it's especially interesting that so much of it is present
in the form of starch-like materials.
Many
people are claiming that fructose consumption has increased greatly in
the last 30 or 40 years, and that this is responsible for the epidemic
of obesity and diabetes. According to the USDA Economic Research
Service, the 2007 calorie consumption as flour and cereal products
increased 3% from 1970, while added sugar calories decreased 1%.
Calories from meats, eggs, and nuts decreased 4%, from dairy
foods decreased 3%, and calories from added fats increased 7%. The
percentage of calories from fruits and vegetables stayed the same. The
average person consumed 603 calories per day more in 2007 than in 1970.
If changes in the national diet are responsible for the increase of
obesity, diabetes, and the diseases associated with them, then it would
seem that the increased consumption of fat and starch is responsible,
and that would be consistent with the known effects of starches and
polyunsaturated fats.
In
monkeys living in the wild, when their diet is mainly fruit, their
cortisol is low, and it rises when they eat a diet with less sugar
(Behie, et al., 2010). Sucrose consumption lowers ACTH, the main
pituitary stress hormone (Klement, et al., 2009; Ulrich-Lai, et al.,
2007), and stress promotes increased sugar and fat consumption
(Pecoraro, et al., 2004). If animals' adrenal glands are removed, so
that they lack the adrenal steroids, they choose to consume more sucrose
(Laugero, et al., 2001). Stress seems to be perceived as a need for
sugar. In the absence of sucrose, satisfying this need with starch and
fat is more likely to lead to obesity.
The
glucocorticoid hormones inhibit the metabolism of sugar. Sugar is
essential for brain development and maintenance. The effects of
environmental stimulation and deprivation-stress can be detected in the
thickness of the brain cortex in as little as 4 days in
growing rats (Diamond, et al., 1976). These effects can persist through a
lifetime, and are even passed on transgenerationally. Experimental
evidence shows that polyunsaturated (omega-3) fats retard fetal brain
development, and that sugar promotes it. These facts argue against some
of the currently popular ideas of the evolution of the human brain based
on ancestral diets of fish or meat, which only matters as far as those
anthropological theories are used to argue against fruits and other
sugars in the present diet.
Honey
has been used therapeutically for thousands of years, and recently
there has been some research documenting a variety of uses, including
treatment of ulcers and colitis, and other
inflammatory conditions. Obesity increases mediators of inflammation,
including the C-reactive protein (CRP) and homocysteine. Honey, which
contains free fructose and free glucose, lowers CRP and homocysteine, as
well as triglycerides, glucose, and cholesterol, while it increased
insulin more than sucrose did (Al-Waili, 2004). Hypoglycemia intensifies
inflammatory reactions, and insulin can reduce inflammation if sugar is
available. Obesity, like diabetes, seems to involve a cellular energy
deficiency, resulting from the inability to metabolize sugar.
Sucrose
(and sometimes honey) is increasingly being used to reduce pain in
newborns, for minor things such as injections (Guala, et al., 2001;
Okan, et al., 2007;
Anand, et al., 2005; Schoen and Fischell, 1991). It's also effective in
adults. It acts by influencing a variety of nerve systems, and also
reduces stress. Insulin is probably involved in sugar analgesia, as it
is in inflammation, since it promotes entry of endorphins into the brain
(Witt, et al., 2000).
An
extracellular phosphorylated fructose metabolite, diphosphoglycerate,
has an essential regulatory effect in the blood; another fructose
metabolite, fructose diphosphate, can reduce mast cell histamine release
and protect against oxidative and hypoxic injury and endotoxic shock,
and it reduces the expression of the inflammation mediators TNF-alpha,
IL-6, nitric oxide synthase, and the activation of NF-kappaB,
among other protective effects, and its therapeutic value is known, but
its relation to dietary sugars hasn't been investigated.
A
daily diet that includes two quarts of milk and a quart of orange juice
provides enough fructose and other sugars for general resistance to
stress, but larger amounts of fruit juice, honey, or other sugars can
protect against increased stress, and can reverse some of the
established degenerative conditions.
Refined
granulated sugar is extremely pure, but it lacks all of the
essential nutrients, so it should be considered as a temporary
therapeutic material, or as an occasional substitute when good fruit
isn't available, or when available honey is allergenic.
REFERENCES
Anaesthesist
1995 Nov;44(11):770-81. [Fructose vs. glucose in total parenteral
nutrition in critically ill patients] Adolph M, Eckart A, Eckart J.
J
Med Food. 2004 Spring;7(1):100-7. Natural honey lowers plasma glucose,
C-reactive protein, homocysteine, and blood lipids in healthy, diabetic,
and hyperlipidemic subjects: comparison with dextrose and sucrose.
Al-Waili NS.
Clin
Ther. 2005 Jun;27(6):844-76. Analgesia and local anesthesia during
invasive procedures in the neonate. Anand KJ, Johnston CC, Oberlander
TF, Taddio A, Lehr VT, Walco GA.
Ann
Nutr Aliment. 1975;29(4):305-12. [Effects of administering diets with
starch or sucrose basis on certain parameters of calcium metabolism in
the
young, growing rat] Artus M.
Calcif
Tissue Int. 2010 Jul;87(1):60-7. The bone histology spectrum in
experimental renal failure: adverse effects of phosphate and parathyroid
hormone disturbances. Batista DG, Neves KR, Graciolli FG, dos Reis LM,
Graciolli RG, Dominguez WV, Neves CL, Magalhães AO, Custódio MR,
Moysés RM, Jorgetti V.
Am
J Primatol. 2010 Jun;72(7):600-6. Sources of variation in fecal
cortisol levels in howler monkeys in Belize. Behie AM, Pavelka MS,
Chapman CA.
Am J Hypertens. 2008 Jun;21(6):708-14.
Hepatic effects of a fructose diet in the stroke-prone spontaneously hypertensive rat. Brosnan MJ, Carkner RD.
Am
J Physiol. 1993 Apr;264(4 Pt 1):E504-13. Whole body and splanchnic
oxygen consumption and blood flow after oral ingestion of fructose or
glucose. Brundin T, Wahren J. "Compared with glucose, fructose ingestion
is accompanied by a more marked rise in CO2 production, possibly
reflecting an increased extrasplanchnic oxidation of lactate and an
accumulation of heat in the body."
Arkansas
Academy of Science Proceedings, Vol. 19, 1965, 59- . Effects of
saturated and unsaturated long chain fatty acids fed with and without
essential fatty acid on
various components of lipid and carbohydrate metabolism. Burgess JT.
J.
Nutr. 1964; 82: 163-172. -Influences of dietary carohydrate-fat
combinations on various functions associated with glycolysis and
lipogenesis in rats. II. Glucose vs. sucrose with corn oil and two
hydrogenated oils. Carroll C.
Am
J Hypertens. 1998;11(5):563-9. Reduction of capillary permeability in
the fructose-induced hypertensive rat. Chakir M, Plante GE, Maheux P.
J Natl Cancer Inst. 1986 Aug;77(2):497-503. Reversal of tumor-induced biochemical abnormalities by
insulin treatment in rats. Chance WT, Muggia-Sullam M, Chen MH, Murphy RF, Fischer JE.
Physiol
Behav. 1988;43(6):765-9. Effect of insulin and 2-deoxy-D-glucose on
feeding and plasma glucose levels in the spiny mouse. Czech DA.
J
Neurobiol. 1976 Jan;7(1):75-85. Effects of environment on morphology of
rat cerebral cortex and hippocampus. Diamond MC, Ingham CA, Johnson RE,
Bennett EL, Rosenzweig MR.
Physiol
Behav. 1984 Jul;33(1):13-20. Food consumption, plasma glucose and
stomach-emptying in insulin-injected hamsters. DiBattista D.
Am
J Physiol. 1989 Oct;257(4 Pt 2):R717-25. Energy expenditure and
diet-induced thermogenesis in presence and absence of hyperphagia
induced by insulin.Dulloo AG, Girardier L.
J
Lab Clin Med. 1980 Mar;95(3):373-85. The effect of age on serum
immunoreactive parathyroid hormone in normal and osteoporotic women.
Gallagher JC, Riggs BL, Jerpbak CM, Arnaud CD.
Diabetes
Care. 2007 Jun;30(6):1406-11. Orange juice or fructose intake does not
induce oxidative and inflammatory response. Ghanim H, Mohanty P, Pathak
R, Chaudhuri A, Sia CL, Dandona
P.
Nutrition.
2005 Feb;21(2):240-8. Changes in lipid metabolism and antioxidant
defense status in spontaneously hypertensive rats and Wistar rats fed a
diet enriched with fructose and saturated fatty acids. Girard A, Madani
S, El Boustani ES, Belleville J, Prost J. "The FS diet resulted in
hypertriglyceridemia but increased the total antioxidant status, which
may prevent lipid peroxidation in these rats."
Diabetologia.
1978 Mar;14(3):191-7. Lipogenesis in situ in the genetically obese
Zucker fatty rat (fa/fa): role of hyperphagia and hyperinsulinaemia.
Godbole V, York DA.
Minerva
Pediatr. 2001 Aug;53(4):271-4. Glucose or sucrose as an analgesic for
newborns: a randomised controlled blind trial. Guala A, Pastore G,
Liverani ME, Giroletti G, Gulino E, Meriggi AL, Licardi G, Garipoli V.
Am
J Clin Nutr. 1989 Jun;49(6):1290-4. Dietary fructose or starch: effects
on copper, zinc, iron, manganese, calcium, and magnesium balances in
humans.Holbrook JT, Smith JC Jr, Reiser S.
Rinsho Byori 1998;46(10):1003-7. Involvement of tau protein kinase in amyloid-beta-induced neurodegeneration. Ishiguro K.
J
Clin Endocrinol Metab 2005; 90(2):1171-5. Polyol concentrations in the
fluid compartments of the human conceptus during the first trimester of
pregnancy: maintenance of redox potential in a low oxygen environment.
Jauniaux E, Hempstock J, Teng C, Battaglia FC, Burton GJ.
Br
J Nutr. 2005 Apr;93(4):485-92. High rates of exogenous carbohydrate
oxidation from a mixture of glucose and fructose ingested during
prolonged cycling exercise. Jentjens RL, Jeukendrup AE. "Furthermore,
exogenous CHO oxidation rates during the last 90 min of exercise were
approximately 50% higher (P<0.05) in GLU+FRUC compared with GLU (1.49
(SE 0.08) and 0.99 (SE 0.06) g/min, respectively)."
Cancer Invest. 2000;18(7):664-9. A medical hypothesis: phosphorus balance and prostate cancer. Kapur S.
J
Lab Clin Med. 1967 Jan;69(1):110-5. Relationship between serum
phosphate concentration and bone resorption in osteoporosis. Kelly PJ,
Jowsey J, Riggs BL, Elveback LR.
J
Vet Sci. 2003 Aug;4(2):151-4. Studies on the effects of biomedicinal
agents on serum concentration of Ca2+, P and ALP activity in
osteoporosis-induced rats. Kim SK, Lee MH, Rhee MH.
Metabolism.
2009 Dec;58(12):1825-31. Effects of
glucose infusion on neuroendocrine and cognitive parameters in Addison
disease. Klement J, Hubold C, Hallschmid M, Loeck C, Oltmanns KM,
Lehnert H, Born J, Peters A.
Endocrinology.
2001 Jul;142(7):2796-804. Sucrose ingestion normalizes central
expression of corticotropin-releasing-factor messenger ribonucleic acid
and energy balance in adrenalectomized rats: a
glucocorticoid-metabolic-brain axis? Laugero KD, Bell ME, Bhatnagar S,
Soriano L, Dallman MF.
Chem
Biol Interact. 2011 May 30;191(1-3):308-14. Metabolic mechanisms of
methanol/formaldehyde in isolated rat hepatocytes: carbonyl-metabolizing
enzymes versus oxidative stress. MacAllister SL, Choi J, Dedina
L, O'Brien PJ.
Mol
Cell Biuochem 2010;341(1-2):149-57. Cytochrome c redox state influences
the binding and release of cytochrome c in model membranes and in brain
mitochondria. Macchioni L, Corazz I, Davidescu M, Francescangeli E,
Roberti R, Corazzi L.
Minerva
Endocrinol 1990 Oct-Dec; 15(4):273-7. [Postprandial thermogenesis and
obesity: effects of glucose and fructose]. Macor C, De Palo C, Vettor R,
Sicolo N, De Palo E, Federspil G.
J Am Coll Nutr. 2000 Feb;19(1):31-7. The interaction between dietary fructose and magnesium
adversely affects macromineral homeostasis in men. Milne DB, Nielsen FH.
J
Clin Endocrinol Metab 2000 Dec;85(12):4515-9. Acute fructose
administration decreases the glycemic response to an oral glucose
tolerance test in normal adults. Moore MC, Cherrington AD, Mann SL,
Davis SN.
J Rheumatol. 2003 Apr;30(4):849-50. Acute gout precipitated by total parenteral nutrition. Moyer RA, John DS.
Chem
Biol Interact. 1995 Oct 20;98(1):27-44. Hepatocyte injury resulting
from the inhibition of mitochondrial respiration at low oxygen
concentrations
involves reductive stress and oxygen activation. Niknahad H, Khan S,
O'Brien PJ. "Furthermore, increasing the hepatocyte NADH/NAD+ ratio with
NADH generating compounds such as ethanol, glycerol, or
beta-hydroxybutyrate markedly increased cytotoxicity (prevented by
desferoxamine) and further increased the intracellular release of
non-heme iron. Cytotoxicity could be prevented by glycolytic substrates
(eg. fructose, dihydroxyacetone, glyceraldehyde) or the NADH
utilising substrates acetoacetate or acetaldehyde which decreased the
reductive stress and prevented intracellular iron release."
Eur
J Pediatr. 2007 Oct;166(10):1017-24. Analgesia in preterm newborns: the
comparative effects of sucrose and glucose. Okan F, Coban A, Ince Z,
Yapici Z, Can G.
Nigerian J. Biochem. Mol Biology 23(1): 12-14, 2008. Depleted blood fructose in diabetes. Osuagwu CG and Madumere HEO.
Menopause.
2011 Sep 15. Improvement in immediate memory after 16 weeks of tualang
honey (Agro Mas) supplement in healthy postmenopausal women.Othman Z,
Shafin N, Zakaria R, Hussain NH, Mohammad WM.
J
Bone Joint Surg Br. 1965 Feb;47:137-9. CHANGES IN SERUM CALCIUM AND
PHOSPHORUS DURING STILBOESTROL TREATMENT OF OSTEOPOROSIS. PARFITT AM.
Endocrinology.
2004 Aug;145(8):3754-62. Chronic stress promotes palatable feeding,
which reduces signs of stress: feedforward and feedback effects of
chronic stress. Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF.
Physiol
Behav. 2009 Mar 23;96(4-5):651-61. An unexpected reduction in sucrose
concentration activates the HPA axis on successive post shift days
without attenuation by discriminative contextual stimuli. Pecoraro N, de
Jong H, Dallman MF.
Cardiovasc Res 2003;59(4):963-70. Reduction of endothelial NOS and
bradykinin-induced extravastion of macromolecules in skeletal
muscle of the fructose-fed rat model. Plante GE, Perreault M, Lanthier
A, Marette A, Maheux P.
Diabetes
Metab. 2005 Apr;31(2):178-88. Consumption of carbohydrate solutions
enhances energy intake without increased body weight and impaired
insulin action in rat skeletal muscles. Ruzzin J, Lai YC, Jensen J.
"Fructose and sucrose solutions enhanced energy intake but did not
increase body weight."
Clin Pediatr (Phila). 1991 Jul;30(7):429-32. Pain in neonatal circumcision. Schoen EJ, Fischell AA.
J.
Clin Invest. 1988; 81:1137-1145. Ethanol causes acute inhibition of
carbohydrate, fat, and protein oxidation and insulin resistance, Shelmet
JJ, Reichard GA, Skutches CL, Hoeldtke RD, Owen OE, and Boden G.
J
Appl Physiol. 1987 Aug;63(2):465-70. Regulatory alterations of daily
energy expenditure induced by fasting or overfeeding in unrestrained
rats. Shibata H, Bukowiecki LJ.
"O2
consumption decreased by 15% on the 1st day of fasting and then by an
additional 15% on the 2nd day. On the 3rd day, when rats were fed again,
energy intake increased by 30% above control (prefasting) values,
whereas energy expenditure rapidly increased
but no more than control values. On the other hand, when ad libitum fed
animals were offered a sucrose solution (32%) for 2 days, energy intake
increased by 30% and energy expenditure by 9-12%. On the 3rd day, when
the rats were fed with their normal diet, energy intake significantly
decreased under control (preoverfeeding) values during one day, but
energy expenditure rapidly returned to normal values. The results show
that fasting decreases, whereas hyperphagia increases 24-h energy
expenditure during the treatments."
Am
J Physiol Endocrinol Metab. 2005 Jun;288(6):E1160-7. Inclusion of low
amounts of fructose with an intraportal glucose load increases net
hepatic glucose uptake in the presence of relative insulin deficiency in
dog. Shiota M, Galassetti P, Igawa K, Neal
DW, Cherrington AD.
Physiol
Behav. 1983 Mar;30(3):325-9. Hyperinsulinemia and its role in
maintaining the hypothalamic hyperphagia in chickens. Sonoda T.
Carbohydr
Res. 2009 Sep 8;344(13):1676-81. Protective role of fructose in the
metabolism of astroglial C6 cells exposed to hydrogen peroxide.
Spasojević I, Bajić A, Jovanović K, Spasić M, Andjus P.
Arthritis Res Ther 2008; 10(5);224. Vascular involvement in rheumatic diseases: 'vascular rheumatology.' Szekanecz Z, Koch AE.
Am J Clin Nutr 1993 Nov;58(5 Suppl):766S-770S. Fructose and dietary thermogenesis. Tappy L, Jequier E.
Biochem
J 1967;102(1):177-80. The influence of fructose and its metabolites on
ethanol metabolism in vitro. Thieden HI and Lundquist F. "without
ethanol... fructose strongly increased the pyruvate concentrtion, which
resulted in a decrease of the lactate/pyruvate concentration
Am
J Physiol Regul Integr Comp Physiol. 2000 Oct;279(4):R1334-40.
Comparison of the effects of sucrose and fructose on insulin action and
glucose
tolerance.Thresher JS, Podolin DA, Wei Y, Mazzeo RS, Pagliassotti MJ.
Bone.
2008 May;42(5):960-8. The effect of feeding different sugar-sweetened
beverages to growing female Sprague-Dawley rats on bone mass and
strength. Tsanzi E, Light HR, Tou JC.
Microcirculation
2003;10(6);463-70. Blood-brain barrier permeability precedes senile
plaque formation in an Alzheimer disease model. Ujiie M, Dickstein DL,
Carlow DA, Jefferies WA.
Physiol Behav. 2011 Apr 18;103(1):104-10. HPA axis dampening by limited sucrose intake: reward
frequency vs. caloric consumption. Ulrich-Lai YM, Ostrander MM, Herman JP.
Am
J Physiol. 1986 Jun;250(6 Pt 1):E607-14. Synergistic improvement of
glucose tolerance by sucrose feeding and exercise training. Vallerand
AL, Lupien J, Bukowiecki LJ.
Diabete
Metab. 1984 Sep;10(3):206-10. [Plasma glucose and C-peptide after
ingestion of sucrose and starch in controlled insulin-dependent
diabetics. Importance of glucose availability]. Villaume C, Rousselle D,
Mejean L, Beck B, Drouin P, Debry G.
Journal
of the American Medical Association
November 10, 2010; Carbohydrate Analysis of High Fructose Corn Syrup
(HFCS) Containing Commercial Beverages. Wahjudi PN, Hsieh E, Mary E
Patterson ME, Catherine S Mao CS, Lee WNP.
Clin
Sci (Lond). 2003 Jun 12. Uric acid reduces exercise-induced oxidative
stress in healthy adults. Waring WS, Convery AA, Mishra V, Shenkin A,
Webb DJ, Maxwell SR.
J
Pharmacol Exp Ther. 2000 Dec;295(3):972-8. Insulin enhancement of
opioid peptide transport across the blood-brain barrier and assessment
of analgesic effect.Witt KA, Huber JD, Egleton RD, Davis TP.
Life
Sci. 1983 Jul 4;33(1):75-82. Serum lipids and cholesterol distribution
in lipoproteins of exercise-trained female rats fed sucrose. Deshaies Y,
Vallerand AL, Bukowiecki LJ.
Am
J Physiol. 1983 Apr;244(4):R500-7. Effects of sucrose, caffeine, and
cola beverages on obesity, cold resistance, and adipose tissue
cellularity. Bukowiecki LJ, Lupien J, Folléa N, Jahjah L.
Am
J Physiol 1987 Sep;253(3 Pt 1):G390-6. Fructose prevents hypoxic cell
death in liver. Anundi I, King J, Owen DA, Schneider H, Lemasters JJ,
Thurman RG.
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