This rebuttal of sorts by Dr. Paul Jaminet was
recently brought to my attention through a comment left on my Facebook
page. Danny Roddy was nice enough to lay out the arguments for me point
by point. Dr. Jaminet’s comments are in red.
1) “I think there’s substantial evidence that high
fructose intake promotes endotoxemia” –PJ
This is not what I have found.
Diabetics and the obese have higher lipopolysaccharide (LPS) levels in
their blood and they consume more fructose, primarily via HFCS, than people who
are not diabetic or obese. But as to specific food effects, the
generation of LPS is buffered against on the ingestion of simple sugars
because, for the most part, simple sugars are completely digested and absorbed
in the upper part of the small intestines where microbial activity is minimal
to non-existent.
It is, however, conceivable that HFCS could lead to the generation of
LPS because of the the presence of large starch molecules, if you recall.
Starch molecules, particularly when insufficiently cooked, can circumvent
digestion and provide fodder for bacteria in the lower intestines, leading to
the generation of LPS.
Endotoxemia occurs, though the definition is arbitrary, when blood
levels of LPS rise by about 2- to 3-fold above normal levels. Fats, in
this regard, by permitting the passage of LPS into the body at high rates via
newly made chylomicrons, execute the damages of LPS initiated by the increased
proliferation of microbes in the intestines that was promoted by starches.
2) “The fact that many researchers use very high doses
of fructose (in order to generate clear results in a reasonably short period of
time) doesn’t prove that fructose is benign at lower doses” –PJ
This is a straw man. I’m not saying that fructose is safe or
beneficial merely because researchers employ high doses of it for the purpose
of hastening the development of toxic effects in animals. I’m instead
saying that arguments should be established on studies in which fructose is (1)
administered in the way it’s eaten in the real world (i.e., with glucose) and
(2) given in more moderate and realistic doses (i.e., as reflected by
consumption data).
3) “Kim seems to think it’s a good sign that “fructose
ingestion induces thermogenesis”. However, in my view thermogenesis is a bad
sign. It implies the presence of an energy excess (or a toxic macronutrient)
which had to be disposed of.” –PJ
Diet-induced thermogenesis consists of (1) the energy costs of
digesting, absorbing, and storing ingested nutrients and (2) the dissipation as
heat, by the activation of the brown adipose tissue, which is blunted in
obesity,1 diabetes,2 and old age, of ingested nutrients.
I don’t see this as a ‘bad sign’ or even the presence of ‘nutrient
excess.’ This is because when isocaloric amounts of fructose and glucose
are compared, studies show that fructose increases energy expenditure and total
carbohydrate oxidation significantly more than glucose does throughout the
whole body. Studies also show that when fructose is exchanged calorie-for-calorie
for glucose, weight loss becomes accelerated.
One way that fructose leads to greater thermogenesis than glucose is
by shifting the cell’s energy charge. Although this effect is subtle,
fructose accomplishes this by (1) rapidly consuming phosphate via bypassing a
key regulatory step in glycolysis and (2) by converting more readily to
glycogen, while consuming twice as much ATP in the process, compared glucose.
Also, fructose, without insulin, apparently activates brown adipose
tissue (that are loaded with uncoupling proteins) in conjunction with thyroid
hormone, adrenalin, and noradrenalin3–5.
Nutrients, therefore, are processed for heat rather than energy (ATP).
To what extent diet-induced thermogenesis contributes to long-term
body fat regulation, I’m not sure. But fructose (and sucrose) is less
likely to lead to an increase in body fat than glucose (and starch) because
compared to glucose, the ingestion of fructose, as a conservative estimate,
leads to a 10-fold greater increase in energy expenditure than glucose does for
hours after consuming it.
Consider what would happen if you conducted a study, where 100
subjects were enrolled and instructed to consume a 2,000 calories diet, 50
percent of which would come from carbohydrates. You then assign half of
the subjects to consume only sucrose, and the other half of the subjects to
consume only glucose for a year.
The subjects would eat 3 square meals a day, so they can be conceived
to be in the “fed-state” for about 16 hours of the day. Again, we would employ
the conservative estimate that fructose leads to a 10-fold greater increase in
energy expenditure during the “fed-state” than glucose does.
So, let’s say that fructose increases energy expenditure by 0.08
calories per hour per gram of fructose ingested, and glucose increases energy
expenditure by 0.008 calories per hour per gram of glucose ingested.
Based on these rates, fructose leads to an increase in energy expenditure of
320 calories over the course of a day.
(.08 calories/hour) x (16 hours) x (250 grams of
fructose) = 320 calories.
Glucose, on the other hand, leads to an increase in energy expenditure
of 32 calories over the course of a day.
(.008 calories/hour) x (16 hours) x (250 grams of
glucose) = 32 calories.
Therefore, the sucrose only group would be expending an extra 176
calories per day (160 + 16), whereas the glucose only group would be expending
an extra 32 calories per day. At the end of the study, the sucrose only
group would expend an extra 63,360 calories (175 x 30 x 12), whereas the
glucose only group would expend an extra 11,520 calories (32 x 30 x 12)—a
difference of 51,840 calories.
Because a pound of fat contains approximately 3,5000 calories, simply
replacing sucrose for glucose in the diet, changing nothing else, would, in
theory, lead to a decrease of slightly less than 15 pounds of body fat over the
course of a year (51,840 ÷ 3,500).
4) “…the healthiest diet is the diet that eliminates hunger
with the smallest calorie intake.” –PJ
Rather than the one that terminates hunger, I posit that the
healthiest diet is the diet that allows us to eat the most, while minimizing
the likelihood of gaining weight. In other words, the healthiest diet is
the diet that keeps the body temperature and metabolic rate optimized.
After all, heat is necessary for optimal biochemical activity of enzymes
throughout the body, and the continuous supply of energy (ATP) is the basis for
the organization and functioning of living cells. Carbohydrates serve
these purposes well, and they do so much better than fats do.
5) “…We even know the mechanism by which this happens:
fructose depletes ATP in the liver, causing the release of adenosine, which is
degraded to uric acid.” – PJ on fructose and uric acid
This has been overturned recently. It turns out that at least
200 grams of pure fructose is needed for the toxic, uric acid increasing effect
to kick in.6
Fructose does, in fact, deplete ATP more than glucose does simply because
of the nature of its metabolism, but the effect is subtle and not necessarily
undesirable. By rapidly depleting the
high-energy phosphate bonds of ATP, fructose (1) forces glucose to be used at a
higher rate and (2) depletes the reducing cofactor called NADH, which is a good
thing (and a topic for a whole other post).
So, through these dynamic processes the excessive accumulation of ADP,
AMP, and adenosine (which irreversibly diffuses out of the cell and is
ultimately degraded to uric acid) is effectively kept in check, and ATP levels
inside cells don’t decrease too much.
6) “I won’t go further through his whole series, I’ll
just observe that it’s easy to go astray when you focus on molecular
biomarkers, hormones, or short-term responses to meals…If you look at our book,
very rarely do we mention any of the body’s hormones or intermediate signaling
molecules and base any argument on their levels. We argue from evolutionary
lines of argument, or from direct links between nutrients themselves and
diseases. This greatly reduces the chances of going astray.” - PJ
I tend to stay clear of ‘evolutionary lines of argument’ because
they are subject to a bit too much speculation for my taste, put too much focus
on “traditional diets” that differ wildly between populations, and ignore the
experiments in which animals reared in “artificial” settings live significantly
longer than their counterparts living in the wild.
Diseases with direct links to nutrient deficiencies have been
established, and for the most part, conquered in developed parts of the
world. Keshan disease, for instance, which is a syndrome that occurs
where selenium is deficient in the soil, has been largely eradicated by the
fortification of foods with selenium. In
parts of China where selenium is lacking, selenium is given in
salt, and this practice has dramatically reduced the incidence of Keshan disease.
The subtleties of the effects of nutrients in the body, however, can
only be appreciated with an integrated understanding of nutrients’ metabolism
in the body, and this includes their interactions with hormones and
intermediate signaling molecules. Take for example iodine, which is
needed for thyroid hormone synthesis. Too much iodine suppresses the
thyroid gland but when given in just the right amount, optimizes thyroid
hormone synthesis. Thyroid hormone, in turn, donates iodine to immune system
cells called neutrophils that then, using iodine, produce bactericidal
compounds to clear away infections.
This bidirectional effect of iodine on the thyroid gland occurs fairly
quickly, so the anti-infective effect of iodine can’t be comprehended, nor can
doses of iodine be properly titrated, in the absence of hormonal data.
Although I agree with Dr. Jaminet that the short-term effects of meals
should be taken with a grain of salt, I don’t think that they should be all
together ignored, as they can serve as cues for consequences to come.
For instance, people who have a tendency to become hypoglycemic
several hours after eating are at a very high risk for developing
diabetes. This is because, in response to hypoglycemia, the
counterregulatory hormones are released, and the habitual, intensive release of
these counterregulatory hormones over time could lead to insulin resistance and
inhibit insulin secretion.7
These people require more support than others in the form of fructose
that buffers against hypoglycemia and helps to moderate blood glucose levels,
extra fat and protein with meals to slow the absorption of nutrients, more
frequent meals, etc.
References
1. Jung, R. T.,
Shetty, P. S., James, W. P., Barrand, M. A. & Callingham, B. A. Reduced
thermogenesis in obesity. Nature 279, 322–3 (1979).
2. Golay, A. et al. Glucose-induced
thermogenesis in nondiabetic and diabetic obese subjects. Diabetes 31,
1023–8 (1982).
3. Acheson, K., Jéquier, E. & Wahren,
J. Influence of beta-adrenergic blockade on glucose-induced thermogenesis in
man. The Journal of clinical investigation 72, 981–6 (1983).
4. De Pergola, G., Giorgino, F., Benigno,
R., Guida, P. & Giorgino, R. Independent influence of insulin,
catecholamines, and thyroid hormones on metabolic syndrome. Obesity (Silver
Spring, Md.) 16, 2405–11 (2008).
5. Young, J. B., Weiss, J. & Boufath,
N. Effects of dietary monosaccharides on sympathetic nervous system activity in
adipose tissues of male rats. Diabetes 53, 1271–8 (2004).
6. Wang, D. D. et al. The Effects of
Fructose Intake on Serum Uric Acid Vary among Controlled Dietary Trials 1 – 4.
(2012).doi:10.3945/jn.111.151951.kidney
7. Ahrén, B. & Lundquist, I. Effects of
alpha-adrenoceptor blockade by phentolamine on basal and stimulated insulin
secretion in the mouse. Acta physiologica Scandinavica 125, 211–7
(1985).
