From: caf@omen.UUCP (Chuck Forsberg)
Subject: Adiposity 101 3/3
Archive-Name: adiposity.101/part03
Organization: Omen Technology Inc
Date: Tue, 17 Nov 1992 13:41:38 GMT
Submitted-By: caf@omen

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Committees reviewing the use of human subjects in these
experiments should not assume that they are ethically
uncomplicated.  The low probability that information of
therapeutic value will result from such a study should weigh
heavily in any deliberation on whether to authorize it."
X
"I can see little reason for intake restriction to receive
continued support, either as a subject of research or as an
accepted therapy for obesity.  Bloodletting as a therapy for
pneumonia was abandoned about a century before penicillin
was discovered.  It required a modicum of courage and good
sense on the part of practitioners who turned away from the
practice, but there is no reason to believe their patients
suffered from this lack of therapy."
X
"A survey of studies published 1977-1986 and reporting on
dietary or behavioral treatment of obesity reveals that the
maximum percentage of body weight lost is, on average, 8.5
percent - no different from the value, 8.9% in similar
studies from 1966-1976, as reviewed by Wing and Jeffery."
X
"The goals and research methods of studies on dietary
treatments for obesity are overdue for ethical as well as
scientific reevaluation.  The same may be said for the
numerous programs providing such treatment outside the
context of research."
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A final footnote on combining diets and exercise.  A Harvard
Health letter compared results of 1982 and 1991 surveys of
doctors' lifestyles.  Since 1982 the doctors reduced their
consumption of red meat, fat, and cholesterol.  They
increased their dietary fiber and exercised more.
Unfortunately, the increased attention to diet and exercise
did not produce leaner bodies; the proportion reporting
weight problems increased from 29 to 39 per cent.
X
While diet evangelists continually assert that new wrinkles
in 60+ year old treatments are improving weight loss
outcomes, the long term success rate of even the best
available weight loss programs using diet, exercise, and
behavior modification remains less than five per cent. (NIH
conference on voluntary weight loss, Mar 30-Apr 1 1992)
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7.  FLAWED RESEARCH
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The quality of diet research and media coverage on the
problem of adiposity often leaves much to be desired.  The
vast majority of this research is so sloppy it would never
be accepted by the FDA as proof of an ethical drug's
efficacy.
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The reader should beware of two common flaws in popular
obesity studies:
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7.1  Correlation .vs. Cause and Effect
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A typical correlation study might show that joggers are
thinner than couch potatoes.  This is a *correlation*.  Such
data are generally accepted as proof that obesity is caused
by lack of exercise, with the implication that fat couch
potatoes will become thin if only they get off their lazy
butts and exercise.
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What is the error in drawing such a conclusion?  The error
is the unstated assumption that the correlation proves a
particular cause and effect.  In fact, other cause and
effect relationships may be involved.  Conventional wisdom
concludes: Lack of exercise causes obesity.  The other
explanation for the observed correlation is: Obesity and
associated impaired muscle development makes sports
activities unpleasant and frustrating if not impossible.
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"While the link between exercise and health in some large
epidemologic studies seems powerful, intervention and
outcome studies suggest a more qualified correlation. ...
Yet "we still have no clinical trial to demonstrate that
increasing activity in a group of sedentary people reduces
the rate of disease vs sedentary controls," says William
Haskell, PhD, also a member of the Stanford faculty." (JAMA
June 12, 1991)
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Correlation studies that draw conclusions or make
recommendations without properly evaluating alternative
models of causality are fundamentally flawed and must be
treated with suspicion.
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7.2  Flawed Sample Selection/Distribution
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Non-random selection or partitioning of the sample
population flaws many studies that otherwise appear to be
well designed.
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One cannot allow subjects to select which experimental group
they will join because the selection process may be stronger
than the experiment.  News media might not understand the
implications, but the study will be flawed.
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For example, a study on the mortality effects of obesity was
based on patients who had repeatedly lost and regained
weight, compared to lean individuals.  Was the higher
mortality caused by obesity, by the dieting, or did diet
cycling cause both?
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Diet studies typically exclude dropouts from their data.
This is not acceptable in weight loss research because
dropouts generally have lower weight loss and greater weight
regain.  Excluding even a few such data points distorts the
experiment because the variability between subjects is much
greater than the average weight loss (SD >> M).
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Studies comparing the relative success of alternative
treatments rarely assign subjects to the alternatives at
random.  The factors that determined sample selection and
partitioning may be more important than the alleged
independent variable.
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8.  TRUTH IN RESEARCH PAPERS
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The honesty and integrity in life sciences research has
increasingly come under question.
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We understand the pressure on a corporation or trade
institute to manage information about the safety and
efficacy of its products and services.  Such pressures are
not limited to the corporate sector.  Weight loss
researchers live by the "publish or perish" syndrome.
Exaggeration of weak results is sometimes a necessary
expedient to secure continuing research funding.  "When all
you have is a hammer, everything starts to look like a nail"
applies to research projects.
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"It is seldom necessary to list individual results in a
paper.  Data can usually be summarized by a measure of
location and a measure of dispersion.  A common practice is
to list the arithmetic mean, standard deviation (S.D.) and
the number of observations (n) used to estimate these
statistics.  If only a few observations are available the
dispersion is better indicated by the range.  If the
distribution is significantly skewed [not a "normal
distribution"] both the median [50th percentile] and range
[minimum and maximum] should be cited." (Journal of
Endochrinology, 1992)
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How can one spot "fudged" research?  One way is to look at
the way data is presented.  If mean (average) values for the
experimental groups are presented, check the standard
deviation values.  The standard deviation must be small
compared to the reported differences between groups.  If the
standard deviation is comparable to the differences between
groups, the data can not be used to analyize individuals.
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Diet evangelists dismiss or downplay the importance of
genetics and other inborn differences affecting the
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development of obesity.  Large standard deviations highlight
the biological differences between fat and thin people.  If
the standard deviation is not disclosed, the researcher is
hiding something from the reader.
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#Diet studies typically exclude dropouts from their data.
This is not valid in weight loss research because dropouts
generally have lower weight loss and greater weight regain.
Excluding even a few such data points generates a false
positive finding because the variability between subjects is
much greater than the average weight loss (SD >> M).  Goal
directed programs and programs that insist that subjects
will succeed if only they follow the regimen provoke highly
skewed dropouts.
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#Weight loss studies often present the average weight loss
of a subset of the experimental cohort.  Most such samples
are not representative of the overweight population, yet
vital questions of relevance to the overweight population
are rarely addressed.  What portion of the overweight
population was not eligible for or excluded from the
program, thus introducing selection bias?  (Williamson &
Levy, Int J of Obesity, 1988)
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#Long term studies pose further problems for studies without
a non-dieting control group.  Williamson and Levy analyzed
weights recorded for medical purposes at two clinic visits
separated by intervals of 1 to 5 years.  These were 332
adult patients who were initially at least 20 per cent
overweight.  The 59 patients measured over a 5 year interval
showed an "apparent weight loss" for 31 per cent of this
group with a mean decrease of 7.3 kg.  This long term random
weight loss is comparable to the positive results reported
by some diet and behavior programs.
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Unless a significant loss beyond baseline is demonstrated by
weight loss studies and programs, no effect should be
attributed to the program.  Control groups that account for
random weight changes (mostly from unsupervised dieting) are
essential in studying the long-term maintenance of weight
loss.
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Any study that takes weight loss as a goal should include
the following information:
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X   + Weight, height, and Body Mass Index (BMI) for subjects
X     at entry, then weight and BMI at each follow-up time.
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X   + Number and size of fat cells before slimming, after
X     slimming, and after weight regain.
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X   + When expressed as means, these values should be
X     accompanied by the standard deviation, not the standard
X     error.
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X   + Data for males and females should always be separated.
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X   + If the study contains more than one experimental group
X     and/or a control group, subjects must be randomly
X     assigned to each group.
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X   + If the study contains more than one experimental group
X     and/or a control group, the data should be presented
X     for each group.
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X   + Studies with 50 or fewer subjects should present
X     individual data.
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X   + Data should include followup for a minimum of three
X     years after treatment ends.
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X   + If there are drop-outs, the remaining number of
X     subjects should be recalculated and reported along with
X     the mean weight at follow-up.  Almost all drop-outs
X     regain their weight loss or more, and must be
X     calculated this way.
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X   + Weight loss studies should report the number and size
X     of adipose cells before slimming, after slimming, and
X     after weight regain.
(Based on recommendations by by William Bennett,  Harvard
Medical School Health Letter)
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9.  MEDIA DISTORTION
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Heavy advertising, a "thin is in" ethic, media preoccupation
with unusually obese individuals, and built-in repeat
business have bloated the diet industry into a 33 billion
dollar a year enterprise.
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As Professor Garner's 1990 testimony before the House of
Representatives indicated, false advertising is rampant in
the diet industry.  While an individual deceptive diet ad
may not be too misleading to the public at large, the
collective effect of such deception (Nazi Big Lie effect)
creates great damage.
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Weight Watchers, Nutri/Systems and other diet promoters
refuse to divulge their long term weight loss data.
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Misleading advertising is, unfortunately, normal for the
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diet industry.  The majority of diet food products tested
for the New York state Consumer Protection Board contained
more calories than listed on their package labels.  80
percent of the diet food products tested exceeded claimed
calories, some by as much as 73 calories per serving.
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10.  NEW TECHNOLOGY
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10.1  STIMULATION OF THERMOGENISIS
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Thermogenisis refers to the generation of body heat in
muscle and brown adipose tissue (BAT).4 Lean subjects
increase thermogenisis in response to meals, exercise, and
cold weather.  Obese subjects show less of each of these
responses than lean subjects.  Obese subjects are less
tolerant to long term cold exposure because of their
inferior thermogenisis capability.
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These facts have prompted many investigations into the
possibility of reducing obesity by increasing thermogenisis
in the obese.
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In their book "Life Extension Weight Loss", Pearson and Shaw
suggest thermogenisis enhancing drugs and cold exposure as
ways to burn up fat.
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Caffeine, ephedrine, nicotine and other materials have been
shown to increase metabolism in humans.  Aspirin increases
the thermogenic effectiveness of ephedrine in obese but not
lean women.  Some are associated with weight loss during the
treatment period.  Common side effects of such treatment
include high blood pressure and heart palpitations.
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#Ephedrine quadrupled the weight loss of obese women whose
metabolisms had been depressed by previous dieting.
(International Journal of Obesity, 1987: 163-8)
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A double-blind Danish study reported that ephedrine 20mg +
caffeine 200mg administered three times daily dramatically
increased fat loss and fat oxidation (see "fast fibres") and
reduced loss of fat-free mass.  Three of the 8 patients on
E+C complained of insomnia, palpitations, and tremor,
respectively.  (Metabolism, 41;7 July 1992)
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X 4. There is some controversy about the location of
X    thermogenisis in adults (BAT or muscle tissue).
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Smokers gain weight when they quit smoking; their final
weight averages the same as that of non smokers.  This
suggests nicotine reversibly depresses weight, 6 to 7 per
cent according to University of Wisconsin researcher Richard
Keesey.  Nicotine reduces weight by increasing metabolism,
not by reducing appetite or food intake.  A growing number
of young women have discovered this, and cigarette smoking
is gaining popularity as a weight control measure.
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Pearson and Shaw recommend nicotinic acid to increase
thermogenisis and as a recreational drug.
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A study of obese women on a swimming program suggests their
heat loss to water had the opposite effect, increasing their
fat stores.  It's been reported that women gain 10 pounds in
less than a week's time when they move to Alaska; they lose
this weight when they move back to a warmer climate.  #This
weight gain may be the result of BAT lipogenesis.
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It has been suggested that early exposure to cold might
promote adult leaness.  (p. 75, Obesity and Leanness - Basic
Aspects) Improvements in household heating in this century
may account for an increase in obesity.
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10.2  GROWTH HORMONE TREATMENT
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The pituitary gland releases Human Growth Hormone (HGH) in
bursts, mostly during the early hours of sleep.  Human
Growth Hormone promotes muscle growth and fat loss.  The
obese produce much less HGH than normal.
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Obesity is associated with reduced 24 hour integrated
concentrations of growth hormone (IC-GH) and elevated
concentrations of insulin (IC-I) compared to lean
individuals.  The difference in growth hormone levels is
greatest in childhood.  The difference in growth hormone
between lean and obese children that IC-GH of obese children
are typical of poorly growing  children with classical
growth hormone (GH) deficiency.  In contrast to children
with classical GH deficiency, obese children are generally
normal or above average for height, growth rate, osseous
maturation and IGF-1 levels.
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A study reported in the Dec 3 1990 Wall Street Journal
reported that short children treated with growth hormone
lost a "drastic 76 per cent of body fat" while gaining as
much as 25% lean body mass (compared to untreated controls).
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Obese individuals normally release very little or no
detectable HGH.  Even under the most strenuous exercise,
obese individuals release only a small fraction of the HGH
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lean sedentary individuals release in normal sleep.
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A study of lipid metabolism in lean and pre-obese swine
(pigs of normal weight which will become fat) indicated low
levels of growth hormone at least until sexual maturity, and
an enhanced deposition of blood lipids as fat compared to
lean subjects. (International Journal of Obesity 1990, 14,
21-29) This enhanced deposition is significant in two ways.
First there is the direct accumulation of fat.  Secondly
this deposition of fat "short circuits" metabolism of blood
lipids into cholesterol and steroid hormones.  This theory
helps explain why destruction of fat tissue allows animals
to grow up with more muscle mass than identical but
untreated controls.
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In the future, high risk babies might be given lipid
tolerance tests, and pre-obese individuals treated with HGH
and DHEA to keep them from becoming fat.
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In a recent study, administration of synthetic growth
hormone to elderly male patients to normalize their low HGH
levels resulted in significant muscle gain and fat loss.
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A Dutch study 8 GH deficient patients reported that 6 months
GH therapy increased lean body mass and decreased fat mass.
The sense of well-being improved in most patients.
Cholesterol levels decreased.  (Clinical Endocrinology 1992
37, p. 79)
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A study at St. Thomas' Hopsital in London found that
patients with hypopituitarism have altered body composition
and quality of life.  In comparison with a matched control
group such patients had considerably reduced lean body mass
and increased fat mass and waist to hip ratio.  A number
were significantly depressed, sufficient to justify therapy.
"We conclude that there is a morbid syndrome associated with
growth hormone deficiency in adult life which responds
dramatically to hormone replacement.  To be effective this
therapy has to be continued indefinitely."
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Exogenous GH increases lean tissue and reduces body fat in
obese women in the absence of significant energy
restriction.  (Hormone Research 1991, 19-24)
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Obese men manifest fewer GH secretory bursts per 24 h and
accelerated HGH disposal rates.  (Journal of Clinical
Endocrinology and Metabolism 72:1 p. 51)
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HGH may be useful in reducing diet-induced loss of lean
tissue.
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10.2.1  Growth Hormone Stimulation  HGH is expensive.  An
alternative to HGH injection is to stimulate the body to
excrete HGH.
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Pearson and Shaw recommend stimulation of human growth
hormone (HGH) excretion with arginine amino acid supplements
as a weight loss method.  Unfortunately, the references
given in their book indicate their recommended amino acid
megadosage is still orders of magnitude too small to cause
the obese to release detectable amounts of HGH.
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The obese have a high threshold which must be surpassed by
strenuous exercise (to the point of exhaustion) or
"incredible" doses of amino acids (orders of magnitude more
than even Pearson&Shaw recommend) before any stimulation of
HGH release is noted.  HGH levels achieved under these
exceptional conditions are still only a fraction of what
lean subjects spontaneously produce in their sleep.
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Long term propranolol therapy increases body weight in heart
attack patients (2P-14); this may modify some of Pearson and
Shaw's recommendations.
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"Chronic ingestion of L-dopa (an HGH releaser) leads to
sustained but reversible weight loss in both lean and obese
Zucker rats."
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10.3  DHEA TREATMENT
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Dehydroepiandrostone (DHEA) reduces weight gain in the
hypercorticosteronemic Zucker fatty rat, an animal of
genetic obesity.  Its chronic anti-obesity effect is thought
to reflect a chronic antiglucocorticoid activity.  (Int J of
Obesity, 1992, 579-)
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University of Wisconsin researchers treated normal and 19
spontaneously obese dogs with DHEA.  The normal weight dogs
did not reduce weight or energy intake.  Two-thirds of the
obese dogs lost 20 percent of their excess body weight and
dropped cholesterol levels by nearly 25 percent without
reduction in food intake.  (Int J of Obesity 1990, 14,95-
104)
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The 1990 Journal of Nutrition reported that DHEA treatment
reversed dietary induced obesity (from a mixture of corn oil
and condensed milk) as well as genetically induced obesity
(fa/fa rat).
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In premenopausal obese women, DHEA levels are inversely
proportional to BMI.  Adipose cells remove DHEA from the
bloodstream; enhanced removal of DHEA in severely obese may
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account for their impaired sensitivity to caloric
restriction.  (Metabolism, Feb 91, p 187)
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Pearson & Shaw claim the "DHEA" sold by health food stores
is bogus.  The author of "The Vitamin Bible" reports
successful personal weight loss with DHEA but gives no
sources or details.
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10.4  RU-486 TREATMENT
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RU-486 causes obese mice to lose weight by getting fat cells
to generate heat rather than store fat.  RU-486 also blocks
the effects of glucocorticoids.  Reportedly RU-486 can help
cure Cushing's syndrome, a gland disorder characterized by
obesity and hypertension.  "Potentially the most potent
anti-aging drug available." (Longevity, Jan 1991) The 1990
American Journal of Physiology reported that RU-486
effectively reversed the obesity of fa/fa rats.
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A paper in the 1992 International Journal of Obesity reports
that Norepinephrine (the neural transmitter, not the asthma
drug) inhibits rat pre-adipocyte proliferation.
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10.5  CoPP TREATMENT
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The 1990 Pharmacology reported that injections of cobalt-
protoporphyrin completely reversed the obesity of Zucker
fa/fa fatty rats to normal.  Significantly, untreated rats
that were fed the same amount of food as the CoPP treated
rats for the first 42 days reverted to the same weight as
untreated fatty rats by day 60.  This indicates CoPP caused
a long term reduction in the rats' set point.
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Typical CoPP treated (left) and untreated (right) Zucker
fatty rats.  Look at this from a distance to get the best
effect.  (B/W Xerographic photocopy of original color plate
was scanned, converted to GIF format by XView, converted to
ASCII with ASCGIF.)
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10.6  CIRCADIAN LIPOSTAT MANIPULATION
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Obesity and type II diabetes may be the result of defective
circadian [daily cycle] neuroendocrine rhythms.
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#Albert Meier, professor of zoology at Louisiana State
University, initiated a study of bromocriptine after 25
years of research on animals' body rhythm biology during
migration and hibernation.  What he attempted to translate
to humans was the finding that many animals reduce or
increase their body fat without altering food intake or
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activity levels.  (Insight, Mar 26 1990)
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Meier, Cincotta and Lovell have dramatically reduced body
fat with oral bromocriptine taken orally at times calculated
to reset circadian hormone rhythms to phase relationships
that cause loss of body fat.  Bromocriptine is a dopamine
agonist used to suppress lactation and in treatment of
Parkinson's disease.
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"The phase of the prolactin rhythm differs in lean and fat
sparrows, fish, rats, and humans.  Daily injections of
prolactin in animals at times when the daily peaks occur in
the plasma of lean and fat animals produce the appropriate
decrease or increase in fat stores within two weeks."
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In early clinical trials, without food restriction, body fat
was reduced equivalent to a 420 calorie VLCD, but without
the loss of lean body mass caused by weight loss diets.
Studies with Syrian hamsters investigating whole body
protein turnover indicate this treatment enhances protein
synthesis, redirecting anabolic activities from lipid to
protein.  Apparently the timed bromocriptine treatment
alters the genetically controlled partitioning of nutrients
described in "The response to long-term overfeeding in
identical twins" discussed above.
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In the second study reported in Experientia 48 (March 1992
p. 248-), 15 diabetic subjects were given timed
bromocriptine treatment.  As with the non-diabetic subjects,
all 15 diabetic subjects lost fat.5 Blood glucose dropped
significantly.  Oral hypoglycemic medication was was
discontinued in 3 participants, and glucose levels remained
near normal for at least two months after treatment.  Doses
of hypoglycemic drugs and insulin were reduced in three
other subjects during treatment.
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X 5. That *all* subjects lost fat is significant.  In energy
X    deprivation diet studies, some subjects invariably fail
X    to lose weight.  In long term diet followup, the
X    standard deviation is two or three times as great as the
X    average weight loss because a large minority gain
X    weight, sometimes a great amount.  Without individual
X    data or the standard deviation, one simply cannot judge
X    the true effectiveness of the experimental intervention.
X    Many diet studies suppress this information as it would
X    cause the reader to discount the validity of the claimed
X    results.
X
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 56 -
X
X
X
Blood pressure was also reduced, allowing blood pressure
medication to be discontinued in several.
X
In a telephone conversation (June 1992) Dr. Meier reported
that a third series of clinical trials was underway as part
of the FDA process to approve the treatment as safe and
effective.  He strongly emphasized how critical TIMING is to
fat loss; correct dosage given in the wrong rhythm actually
increases body fat.  (According to the Insight article, the
procedure has been patented.)
X
"Our studies also indicate that a cause-effect relationship
between overfeeding and obesity is oversimplistic and that
food intake and lipid synthesis may be regulated in a
concerted fashion by circadian neuroendocrine activities."
X
10.7  TESTOSTERONE TREATMENT
X
Men with abdominal obesity have low testosterone values.  An
8 month study at the Sahigren's Hospital in Goteborg, Sweden
tested 23 men aged 40-65 years in a double blind experiment
in restoring testosterone levels to normal.  The
testosterone treated group improved in waist size, blood
pressure, plasma lipids, fasting glucose, and insulin
sensitivity.  Normalization of testosterone levels reduced
many of the health warning signs associated with obesity.
X
10.8  BETA3-ADRENOCEPTOR AGONISTS
X
Animal studies on several Beta3-agonists show they fulfill
many of the properties of the ideal anti-obesity drug.
These compounds produce selective loss of body fat mass with
a preservation of lean tissue.  In addition, the changes in
body composition are accompanied by favourable metabolic
changes including improvement in glucose tolerance,
reduction of hyperinsulinemia and hyperlipidaemia.  (S18-3)
X
10.9  SEROTONIN REUPTAKE INHIBITORS
X
"The genesis of this project was an invitation to discuss
anorexiant medications with the house officers in the
Medical CLinic as Strong Memorial Hospital.  The colleague
who invited me was dismayed that the treatment options used
in the medical clinic were not helping people lose weight."
Michael Weintraub, MD "both the medical profession and
society look with disfavor on obese people and obesity in
general. ... Obese people are treated negatively in cartoons
and in literature.  Many believe that obese people need only
to "close their mouths" and be more motivated to lose
weight.  The use of medications to correct a characterologic
defect is, in the opinion of physicians and the public,
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 57 -
X
X
X
deemed inappropriate.
X
Unfortunately, a lack of understanding of both the natural
history of obesity and its diversity adds to the perjorative
view of obese people and of anorexiants.  Some health
professionals are not aware of data concerning mechanisms
present in the human organism that act to contravene
pertubations in body weight and that may account for the
apparent failure of interventions, including medications."
X
To provide longer-term data, Weintraub et al developed a 4
year multimodal program using state-of-the-art behavior
modification, caloric restriction, and exercise as the
"placebo" for the entire duration of the four year study.
Subjects attended nearly 100 visitations with health
professionals during the study.  When reading reports on The
National Heart, Lung, and Blood Institute funded Multimodal
Intervention Study, please keep in mind that this "state-
of-the-art" treatment was the "placebo".  (State of the
diet/exercise/shrink art, that is!) "From the end of the
second double-blind phase at week 190 through week 210, we
monitored study participants to see what happened without
medication but with continuing behavior modification,
caloric restriction, and exercise therapy. ... One measure
of the excellence of the ancillary [placebo] therapy in this
study was that it enabled participants treated with placebo
to lose just 0.01 kg/week less than participants receiving
active therapy in the 18 studies that lasted at least 8
weeks reviewed by Scoville for the FDA."
X
121 subjects, 18 to 60 years old, mean BMI of 33.4 +- 2.2,
three fourths female, entered the medication phase of the
study after 6 weeks of behavior mod, diet and exercise.  69
per cent had been on six or more diets previously.
X
Subjects on medication lost about three times the weight as
those only receiving behavior modification, diet and
exercise.  There was no indication of tolerance or abuse
potential of the medication.  There was no indication that
use of anorexiant inhibits the learning of behavior
modification.
X
As reported by the New York Times New Service, Dr. Albert
Stunkard, an obesity researcher at the University of
Pennsylvania, said he knew of no other study that had
elicited such a dramatic and sustained weight loss. It
``points to the way things are going to go,'' he said.
X
The investigators found their patients could not maintain
their weight loss without the drugs.
X
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 58 -
X
X
X
The final 30 weeks of the program assessed what happened
when all the patients were weaned from the drugs, relying on
continued diet, exercise and behavior control. They
gradually regained almost all the weight they had lost,
despite the continuing program of diet, exercise and
behavior modification.
X
#Some who believe that the essential defect in obesity is
will power have asserted that the weight regain was from
subjects' going "off the diet" when medication was
withdrawn, instead of the diets' poor long term performance.
A number of facts argue against this assertion:
X
X   + Fenfluramine's appetite reducing effect wears off
X     within a week.  Any increased eating from cessation of
X     the anroectic effect would have occurred much earlier.
X
X   + Patients were on moderate diets, up to 1800
X     caliores/day for men, 1200 for women.  Most of the
X     patients were veterans of a half dozen or more diet
X     attempts.  With this amount of metabolic slowdown, the
X     traditional (diet/exercise/behavior mod) part of the
X     program may not have been able to induce much long-term
X     weight loss without benefit of the drugs' lowering of
X     set point.
X
X   + Lipid profiles, primarily affected by the diet and
X     exercise, confirmed the weight regain was not caused by
X     cheating on the diet.
X
When the study was over, and subjects were nearly as fat as
they were initially, many tried to get the drug combination
from their private doctors and ran into skepticism over the
treatment.
X
Some experts on weight loss hailed the studies, saying they
could mark a pronounced shift in the way obesity is studied
and treated.
X
These experts said the results showed obesity could be
treated the way chronic diseases like high blood pressure or
arthritis are.  In those diseases, drugs must be taken
indefinitely to keep symptoms in check.
X
``This is a landmark study,'' said Dr. George Blackburn, an
obesity researcher at New England Deaconess Hospital in
Boston.
X
Study VI of the report discusses individual outcomes.  One
subject did not reach goal weight (120% of ideal) but he was
able to maintain his weight loss even after medication
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 59 -
X
X
X
ceased.  Some others did reach goal weight but gained it all
back, or more.  Most lost at least some weight but regained
after medication ceased, despite continuing behavior
modification, diet and exercise.  Some lost little or no
weight, or gained weight.  Many of the failures were due to
the experimental protocol which did not allow for individual
adjustments that would have been made in a health care
setting.  Diet evangelists who do not appreciate the deep
biological diversity of fat people should study this paper
(and the papers on identical twins) carefully.
X
X
Serotonin-reuptake inhibiting agents include flouxetine
(Prozac), fenfluramine, and d-fenfluramine (dexfenfluramine,
dF).
X
In France and England, fenfluramine has been used in the
treatment of human obesity for 25 years.  Dexfenfluramine is
the dextro stereoisomer of fenfluramine, and is a more
potent antiobesity agent with fewer side effects.  "The
overall incidence of side effects in our studies was lower
than found in most studies with dl-fenfluramine.  Tiredness
and drowsiness were the most commonly reported unwanted side
effects of treatment, but occurred as frequently with
placebo treatment as with dexfenfluramine." (Clinical
Neuropharmacology Vol 11 Suppl 1 S179)
X
X
The conventional labelling of d-fenfluramine as an appetite
suppressant is hopelessly oversimplified at best, if not
downright inaccurate.  "According to most authors, tolerance
to the anorectic effects of d-fenfluramine in rats rapidly
sets in; food intake is depressed or only 2 to 6 days ...
However, as long as the drug is administrated, the weight
deficit persists." (Clinical Neuropharmacology Vol 11 Suppl
1 S105)
X
#"Following approximately a week of daily ingestion of
fenfluramine, the body weight of female rats is reduced and
remains chronically suppressed for as long as treatment is
continued.  This chronic suppression of body weight by
fenfluramine cannot be explained by the anorectic effects of
fenfluramine, since food intake returns to normal after
about a week.  Part of this chronic suppression of body
weight lies in the ability of fenfluramine to enhance the
thermic effect of food.  Fenfluramine ingested by a fasted
rat causes no change in metabolic rate.  However, following
the ingestion of the meal consisting of mixed nutrients or
only carbohydrates, the thermic effect of the food is
significantly greater than that of the meal without
fenfluramine.  A similar observation was observed in humans.
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 60 -
X
X
X
These observations when combined with the negligible effects
of dieting as a means of controlling body weight, argue for
the chronic use of fenfluramine as a therapeutic technique
to produce sustained weight loss in humans." (Clinical
Neuropharmacology Vol 11 Suppl 1 S90-2)
X
#Is fenfluramine's anorectic effect essential to its
antiobesity properties?  When body weight was reduced in
rats prior to treatment with fenfluramine, administration of
the drug was followed by a rapid increase in food intake
with maintenance of the reduced weight.  The reduced body
weight in fenfluramine-treated rats is defended; when
animals are force fed to a higher weight and then allows to
eat ad libitum their food intake drops and body weight
drops.  (Recent Advances in Obesity Research: V 290)
X
#Fenfluramine normalizes obese subjects' deficient growth
hormone (GH) response to arginine.  (Hormone Research 1987:
27; 190-194)
X
Fluoxetine, another serotonin-reuptake inhibiting agent, has
been shown to improve insulin sensitivity and other
metabolic actions.
X
#Dexfenfluramine is a related drug that increases metabolic
rate (MR), diet induced thermogenisis (DIT), decreases blood
pressure, and enhances glucose clearance.  Dexfenfluramine
reduces or prevents weight regain after slimming.  The drug
appears well suited for use in hypertensive or diabetic
obese patients.  (Clinical Neuropharmacology Vol 11 Suppl 1)
(Progress in Obesity Research 1990) In rat, d-fenfluramine
improves insulin action of reducing the liver's glucose
output.  (DIABETES Apr 1989)
X
The Weintraub study maintains a level of experimental
design, reportage, disclosure and honesty that distinguishes
it from most studies of traditional weight loss techniques.
#It is the longest weight control study of any type.  It
underscores the abject failure of traditional weight loss
technology to improve the quality of life for most fat
people.
X
Free reprints of this 65 page supplement are available.
X
Numerous papers on the antiobesity properties of serotonin-
reuptake inhibiting agents appeared in Vol 11 Supplement 1
of Clinical Neuropharmacology (1988).
X
X
X
X
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 61 -
X
X
X
10.10  FAT CELL REMOVAL
X
10.11  Surgery
X
Surgery is the only currently available fat reduction
treatment that has demonstrated long term success in a
majority of patients.
X
Unfortunately, the amount of fat removed by currently
accepted surgical procedures is too small to be useful for
mainstream weight reduction purposes.
X
A newspaper recently reported an increase in breast size for
women who had "love handles" removed.  It is possible the
breast size was recovering from the effects of stringent
dieting undertaken in unsuccessful attempts to spot reduce
the "love handles".
X
A South African study of freely-eating, non-obese
liposuction patients showed no increase in fat cell size,
metabolic efficiency, or regional adipose distribution 1 to
2 months after surgery.
X
Surgical removal of fat in Cushing's Syndrome patients (4F-
21) resulted in an increase in lean tissue mass, and no fat
regain.
X
Diabetic patients receiving abdominal liposuction have
reduced insulin requirements (dose reduced from 20 to 10
units).  (Unpublished data)
X
Some efforts are underway to develop surgical procedures to
significantly normalize fat cell numbers.
X
10.12  Immunological Manipulation
X
The Hannah Research Institute in Scotland have developed a
treatment to reduce adiposity by targeting cytotoxic
antibodies to fat cells.  In early experiments, rat fat cell
plasma was injected into sheep. The resultant antibodies
were filtered and introduced into the rats.  The treated
rats lost fat.
X
The treated rats also had more lean tissue than untreated
controls.  This suggests fat cells deprive lean tissue of
nutrients necessary for growth.
X
After treatment ended, the rats gained fat in other areas,
restoring a normal amount of fat.  This suggests some higher
level mechanism prevents adipose mass from falling below
norms.  Normal weight rats were used in these experiments;
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 62 -
X
X
X
results may be better for obese humans.
X
In a telephone conversation in 1991 I was told Hannah's
research is proceeding very well toward its goal of
producing leaner animal meat.  Human application in the near
future is unlikely due to risk of malpractice lawsuits.
X
Other researchers, using monoclonal antibodies, report
success in longer term suppression of fat cell numbers.
(Private conversation, 1992)
X
X
11.  PREDICTIONS
X
A portion of the current obesity epidemic will be traced to
nutritional and hormonal problems during pregnancy and/or
infancy.  Pregnancies with gestational diabetes and other
problems that previously failed now produce preobese
children.  The introduction of high carbohydrate baby
formula and sugary baby foods in this century will also be a
factor.  Low fat high carbohydrate weight loss diets applied
early in life will also be implicated.
X
#Within the decade, prescription of energy restriction
weight loss diets for patients with childhood onset obesity
will be recognized as a violation of the Hippocratic Oath.
X
X
12.  RECOMMENDATIONS FOR ACTION
X
Popular attitudes on obesity are based on the notion that
obesity is caused by sloth and gluttony.  Recent research
has discredited this stereotype and suggested possibilities
for effective prevention or treatment in the future.
X
X   + Truth in Advertising must be enforced on all weight
X     loss claims.  Advertising must disclose long term
X     results obtained by typical users, accurately reporting
X     the prevalence of weight regain and overshoot.  The
X     Federal Trade Commission is preparing a crackdown on
X     diet companies.  (Reuter, May 21 1992) The Clinton
X     administration may be more interventionist in this
X     area.
X
X   + Diagnostic procedures are needed to identify the 5 per
X     cent of overweight subjects for whom weight loss diets
X     provide long term benefits.
X
X   + Policies and public education are urgently needed to
X     reduce diet induced adipocyte hyperplasia.  (In
X     English: diets make some fatter and we need to do
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 63 -
X
X
X
X     something about it!) This is an area where malpractice
X     and product liability lawyers can do some good.  The
X     recent lawsuit settlements by Nutri-System Weight Loss
X     Inc. are a promising start, and a meeting on the
X     subject at a recent Trial Lawyers' convention bodes
X     well for the future.  President-elect Clinton's links
X     to trial lawyers and his refusal to criticize
X     malpractice suits may encourage this development.
X
X   + Effective interventions to correct human obesity must
X     be developed and deployed.  Candidates include surgery,
X     immunization to fat cell plasma, CoPP, RU-486,
X     correction of low EGF, testosterone, DHEA and Growth
X     Hormone levels.  One hundred million American
X     endomoprphs deserve more than a few dimes' worth of
X     legitimate obesity research.
X
X   + Doctors should properly diagnose and properly treat the
X     medical conditions of their obese patients instead of
X     insisting on unrealistic weight loss as an alternative
X     or precondition to treatment.
X
X   + Regulatory interference in the development and
X     deployment of effective new treatments must abate.
X     Public health would be better served if regulators
X     shifted their attention to the abuses of the diet
X     industry.
X
X   + Mothers should limit carbohydrate and sugar consumption
X     during pregnancy and lactation.
X
X   + Mothers should breast feed the full recommended time.
X
X   + Babies should not be fed a high carbohydrate diet.
X
"We recognize that the message we have for endocrinologists
and metabolic specialists is a somber one, difficult to the
sufferer from obesity.  On the other hand, it seems to us
most consonant with the true state of affairs.  Our
understanding of genetic mechanisms is progressing rapidly
and the interaction between genetic endowment and early
environment will be under intensive study in the next
decade.  This is the hopeful side of the problem." (CLINICAL
REVIEW 28: A Biological Basis for Human Obesity, Journal of
Clinical Endocrinology and Metabolism, 1991.)
X
X
X
X
X
X
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 64 -
X
X
X
13.  REQUIRED READING
X
Human Obesity: Exploding the Myths The Western Journal of
Medicine Oct 1990; 153;421-428
X
Annals, New York Academy of Sciences, book length issue on
Human Obesity
X
LONG TERM WEIGHT CONTROL:
The National Heart, Lung, and Blood Institute funded
multimodal intervention study, Clin Pharmacol Ther, May 1992
Reprints of the entire supplement are available at no
charge.  Direct requests to:
Michael Weintraub MD
Department of Community and Preventive Medicine
University of Rochester School of Medicine
PO Box 644
Rochester NY 14642
X
Information on the medications used may be obtained with a
self addressed stamped envelope mailed to:
DIET STUDY
University of Rochester Medical Center
POB 643
Rochester NY 14642
X
X
OBESITY AND LEANNESS, Basic Aspects, ISBN 0 86196 0173
X
Never Say Diet? article by Ruth Papazian,  FDA CONSUMER,
article downloaded from the Food and Drug Administration
Bulletin Board.  For copies contact the FDA Publications
Staff at 301-443-3220.
X
X
14.  RECOMMENDED READING
X
References such as (4F-21) refer to paper designations in
the Tokyo Internationl Congress on Obesity abstracted in the
International Journal of Obesity.  Some of these papers
appear in Progress in Obesity Research 1990 (Proceedings of
the 6th International Congress on Obesity), John Libbey &
Sons ISBN 0 86196 274 5
X
"Recent Advances in Obesity Research: V" ISBN 0-86196-072-6
X
"CLINICAL REVIEW 28: A Biological Basis for Human Obesity",
Journal of Clinical Endocrinology and Metabolism, 1991.
X
"Obesity in Europe 88" ISBN 0-86196-167-6
X
X
X
X
X                       Adiposity 101
X
X
X
X
X
X
X
X                           - 65 -
X
X
X
International Journal of Obesity (Periodical)
X
"Fat Chance" Nova episode broadcast on PBS (1983)
X
Annals, New York Academy of Sciences, book length issue on
Human Obesity
X
The Callaway Diet, Bantam non fiction paperback, ISBN-0-
553-28708-7 (C Wayne Callaway, M.D. is the former director
of the Nutrition and Lipid Clinic at The Mayo Clinic, former
director of the George Washington University Medical Center
Center for Clinical Nutrition, and has held prominent
positions with the U.S. Department of Health and Human
Services, and the National Institutes of Health.)
X
"Diet and Health:  Implications for reducing chronic disease
risk"; Committee on Diet and Health Food and Nutrition Board
Commission on Life Sciences, National Research Council;
National Academy Council, Washington D.C.  1989.
X
Progress in Obesity Research 1990 (Proceedings of the 6th
International Congress on Obesity), John Libbey & Sons ISBN
0 86196 274 5
X
"Number and Size of Adipose Tissue Fat Cells in Relation to
Metabolism in Human Obesity" Page 703, Metabolism, Vol 20 No
7 July 1971.
X
"Lean Body Mass, Exercise and VLCD", International Journal
of Obesity (1989), 13 (suppl. 2), 17-25.
X
"Super Nutrition for Women", Ann Louise Gittleman, Santa
Monica Pritikin Longevity Center nutrition director, Bantam
Books, 1991
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X                       Adiposity 101
X
X
X
X
SHAR_EOF
echo 'File adiposity.101 is complete' &&
chmod 0644 adiposity.101 ||
echo 'restore of adiposity.101 failed'
Wc_c="`wc -c < 'adiposity.101'`"
test 150192 -eq "$Wc_c" ||
	echo 'adiposity.101: original size 150192, current size' "$Wc_c"
rm -f _shar_wnt_.tmp
fi
rm -f _shar_seq_.tmp
echo You have unpacked the last part
exit 0

-- 
Chuck Forsberg WA7KGX          ...!tektronix!reed!omen!caf 
Author of YMODEM, ZMODEM, Professional-YAM, ZCOMM, and DSZ
  Omen Technology Inc    "The High Reliability Software"
17505-V NW Sauvie IS RD   Portland OR 97231   503-621-3406