Low-dose growth hormone therapy reduces inflammation in HIV-infected patients

Randomized controlled trial

Lindboe JB, et al. Infect Dis (Lond). 2016 Nov-Dec.

Authors

Lindboe JB1, Langkilde A1, Eugen-Olsen J2, Hansen BR2,3, Haupt TH1, Petersen J1,4, Andersen O1,3.

Author information

  • 1a Optimed, Clinical Research Centre 056, Copenhagen University Hospital Hvidovre , Hvidovre , Denmark ;
  • 2b Clinical Research Centre 056, Copenhagen University Hospital Hvidovre , Hvidovre , Denmark ;
  • 3c Department of Infectious Diseases , Copenhagen University Hospital Hvidovre , Hvidovre , Denmark ;
  • 4d Department of Biostatistics , University of Copenhagen , Copenhagen , Denmark.

Citation

Infect Dis (Lond). 2016 Nov-Dec;48(11-12):829-37. doi: 10.1080/23744235.2016.1201722. Epub 2016 Jul 15.

Abstract

BACKGROUND: Combination antiretroviral therapy (cART) has drastically increased the life expectancy of HIV-infected patients. However, HIV-infected patients exhibit increased inflammation and 33-58% exhibit a characteristic fat re-distribution termed HIV-associated lipodystrophy syndrome (HALS). Recombinant human growth hormone (rhGH) has been tested as treatment of HALS. Low-dose rhGH therapy improves thymopoiesis and fat distribution in HIV-infected patients and appears to be well tolerated. However, since high-dose rhGH is associated with adverse events related to inflammation, we wanted to investigate the impact of low-dose rhGH therapy on inflammation in HIV-infected patients.

METHODS: Forty-six cART-treated HIV-infected men were included in the HIV-GH low-dose (HIGH/Low) study: a randomized, placebo-controlled, double-blinded trial. Subjects were randomized 3:2 to 0.7 mg/day rhGH, or placebo for 40 weeks. rhGH was self-administered between 1 pm and 3 pm. The primary outcome of this substudy was changes in inflammation measured by plasma C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR).

RESULTS: Both CRP (-66%, p = 0.002) and suPAR (-9.7%, p = 0.06) decreased in the rhGH group compared to placebo; however, only CRP decreased significantly. The effect of rhGH on inflammation was not mediated through rhGH-induced changes in insulin-like growth factor 1, body composition, or immune parameters.

CONCLUSION: Daily 0.7 mg rhGH treatment for 40 weeks, administered at nadir endogenous GH secretion, significantly reduced CRP. The effect does not appear to be mediated by other factors. Our findings suggest that low-dose rhGH treatment may minimize long-term risks associated with high-dose rhGH therapy.

Complementary Approaches to Treating Lipodystrophy

From the book: Built to Survive


12. 
Complementary Approaches to Treating Lipodystrophy
By
Michael Mooney
(original version in
Medibolics 2(2),Nov. 1997)


While
the protease inhibitor (PI) cocktails can bring viral loads down to
undetectable levels and have given many HIV(+) people a new lease on life,
protease inhibitors are not always benign drugs. As we approach year four of
the triple-combo era, numerous problems have appeared among people who are on
protease inhibitors. One of the most common of these side effects (and perhaps
the least understood) is the protease belly or Crix belly phenomenon. Crix belly, so named because it
was mostly observed among people being treated with Crixivan, is a condition most notably
marked by the appearance of a large protruding potbelly. (At the same time this
is happening some people report that they feel like they are losing muscle mass
and fat, too, especially in the arms and legs.) Another sometimes concurrent
but rare condition is the so-called buffalo hump, which is a fat pad that
grows on the back of the neck that resembles what is seen in Cushing’s syndrome. Women are also experiencing
an increase in breast size as the breasts seem to gain fat (called lipoma), and many people are losing
fat in their arms, legs, and cheeks while one or more of these other things are
happening to them. Lipodystrophy is the medical term that has been given to
this syndrome, but it can also simply be called bodyfat redistribution.
It
now appears that lipodystrophy is not a side effect entirely specific to
Crixivan. It may be seen with use of any of the available
protease inhibitors, and nucleoside and non-nucleoside analogs. It has also
been seen to a lesser degree in HIV(+) people before protease inhibitors were
available. However, the various cocktails of powerful drugs being used today to
combat HIV seem to increase the severity of this syndrome over the simpler drug
combos of a few years ago, although there is discussion that one of the older
drugs, D4T (Zerit) may play a central role in the problem (visit http://www.facialwasting.org/
pages/891053/index.htm
) . And in some cases, the addition of the appetite
stimulant Megace to the protease inhibitors seems to increase
the potential for bodyfat redistribution.
There
are several reasons why this might happen. The “protease pouch belly” in many
respects resembles the potbelly seen in disease states like Cushing’s syndrome, alcoholic hepatitis, and heart disease. In these
diseases the potbelly is associated with the development of insulin resistance [i] [ii] [iii]  and is primarily composed of enlarged fat
deposits surrounding the visceral organs, like the stomach, and liver, under
the abdominal muscle wall and ribs.[iv] The potential for liver burden or
toxicity induced by many of the common AIDS medications has been documented and
the protease inhibitors are no exception to this rule. Elevated triglycerides,
liver enzymes, and blood glucose and even diabetes have all been observed in patients on protease
inhibitor therapy. All of these conditions are symptoms
of diminished insulin sensitivity, and we are seeing that the protease
inhibitors’ effects on liver metabolism are inducing a state of insulin
resistance in many people who are on protease inhibitor
therapy. Complications of insulin resistance include hyperglycemia (high blood sugar), diabetes, and
cardiovascular disease, and the FDA has documented over 80 cases of diabetes
that appear to be associated with protease inhibitor therapy.
Indeed,
from early 1998, numerous studies have documented an association between the
use of protease inhibitors and measurements that indicate insulin resistance is present including data by
Kathleen Mulligan, Ph.D. of San Francisco
General Hospital, confirming that protease inhibitors can cause the blood
chemistry changes that are typical of insulin resistance;[v]
Dr. Ravi Walli of
Ludwig-Maximilians Universitat Munchen in Germany reporting that peripheral
insulin resistance is common in patients on protease inhibitors;[vi]
and Dr. Andrew Carr of St.
Vincent’s Hospital of Sydney, Australia, detailing his hypothesis of the
cytoplasmic (cellular) retinoic acid-binding protein type I (CRABP-1)
biochemistry involved in the liver dysfunction that may promote insulin
resistance.[vii]
Additionally, some people who are using protease inhibitors are being found to
have accelerated cardiovascular disease, which is also a common outcome of
progressive insulin resistance.
A
look at Harrison’s Principles of Internal Medicine shows us that lipodystrophy
can be associated with insulin resistance, and so we see that the components
in this puzzle, lipodystrophy; elevated triglycerides, elevated blood glucose, elevated insulin levels;
diabetes; cardiovascular disease; and insulin resistance are all appearing.
While
this chapter does not offer a cure for body fat redistribution as protease
belly, buffalo hump, loss of facial fat, or lipoma, it offers tools that are
documented to improve insulin sensitivity that may help people gain some
control over this problem until medical science gains enough of an
understanding to solve it.
Women and Testosterone
Studies
show that HIV(+) women who are losing lean body mass may also need testosterone, 89 but the appropriate dosage of testosterone
enanthate injections for women is usually much lower than the dosage for men,
between 2.5 and 20 mg per week. This is something for a doctor to determine by
taking blood tests, usually two to three days after the fourth weekly injection
for a representative average level. A number of HIV(+) women are using
testosterone creams that are compounded by a pharmacy like Women’s
International Pharmacy (1-800-279-5708). However, testosterone enanthate injections
deliver a longer-lasting blood level of testosterone than the creams, which
have a relatively short life span in the body. If a cream is used, it is
usually applied in a dose of between 2 and 5 mg two times per day, while the
injections are best given once per week, as studies show that testosterone
blood levels generally decline to baseline within about 10 days after
injection.[xix]
As
women are much more sensitive to side effects from testosterone, the physician should monitor
a female closely for any virilizing side effects, which include oily skin, acne, peach fuzz, hair loss, and clitoral enlargement,
and immediately lower the dose or cease the therapy if these kinds of symptoms
start to occur.
Normal Testosterone Levels May Not Be Enough (Men Only)
I
should also note that finding the correct testosterone dose for each individual is not always easy,
as data from studies by researchers like Dr. Judith Rabkin suggest that being HIV(+) can mean that the
normal range for testosterone measurements does not necessarily apply to men.
In her study with HIV(+) hypogonadal men, Dr. Rabkin found that the dose of
testosterone enanthate needed to be above 200 mg every two weeks, for good
quality-of-life. The dosage she found to be effective was 400 mg every two
weeks (which I suggest is best given as 200 mg per week for more consistent
blood levels, less peak/trough effect, and reduced potential for side effects).
At 400 mg given every two weeks the men’s blood testosterone levels averaged
about 1100 ng/dL one week after the fourth injection (on a scale where the
normal range is 300 to 990 ng/dL). In private correspondence Dr. Rabkin said
that she is not sure whether 300 mg every two weeks would yield a satisfactory
result or whether the men would respond satisfactorily if their average levels
only reached 800 ng/dL. She said that some men did receive benefit at about 700
ng/dL though.[xx]
Remember, the bottom of the normal scale was 300, so the normal scale didn’t
seem to apply well to these HIV(+) men.
Free Testosterone
We
assert that some men’s apparent need for testosterone at higher than the standard replacement dose
of 100 mg per week (for HIV-negative hypogonadal men) may be the result of hormonal resistance
to testosterone. Hormonal resistance appears to happen with several hormones in
HIV pathology. However, studies suggest that the need for higher testosterone
doses is most likely caused by elevated sex-hormone binding globulins and
lowered free testosterone,
which is common in HIV.88 [xxi]
When this is the case, total testosterone measurements do not adequately
reflect the person’s state of health.
Supplementing
testosterone to bring free testosterone levels in the body into an optimal range may
be beneficial to hypogonadal men in general, by improving the partitioning
of nutrients more towards lean tissue and less toward fat tissue, especially
visceral fat.[xxii] Significant data also suggests
that appropriate testosterone supplementation can improve blood lipid chemistry
to reduce the potential for cardiovascular disease in men who are deficient.[xxiii]
Testosterone Patches or Creams
We
have reports that application of the Testoderm TTS or Androderm testosterone patches directly on the buffalo hump appears to shrink it. If this works,
testosterone creams or gels might work better as the dose of
testosterone can be much greater than in a patch. While a study of adipocyte
(fat cell) chemistry does provide a rationale as to why application through the
skin might work, application of a cream would not be likely to work to reduce
the belly because of the greater distance from the skin through the stomach
muscles to the fat cells inside.
Anabolic Steroid Improves Insulin Sensitivity and Glucose Disposal
One
study showed that the injectable anabolic steroid nandrolone decanoate (Deca
Durabolin) improved glucose disposal
and lowered insulin levels when administered at 300 mg per week,
while it did not have any effect at 100 mg.[xxiv]
While this injectable beta esterified anabolic steroid may have a beneficial
effect on insulin sensitivity another study found that it appears to enhance
non-insulin-mediated glucose disposal.[xxv]
This study and other studies state that oral 17-alpha alkylated anabolic
steroids, such as oxymetholone (Anadrol-50), oxandrolone (Oxandrin) and stanozolol (Winstrol)
promote insulin resistance because of their effect on liver metabolism.[xxvi]
[xxvii]
This raises questions about using oral steroids when lipodystrophy is present.
The Paradoxical Effects of Oral Steroids
However,
oral steroids can decrease triglycerides (fats) because of
their effect of increasing post-heparin hepatic triglyceride lipase, which
breaks down triglycerides. [xxviii]
[xxix]
For this reason oral steroids may help to decrease visceral fat, although they
promote insulin resistance, and I have heard reports of each
of the oral steroids stanozolol, oxymetholone and oxandrolone reducing the
protease belly in HIV(+) males. Indeed, data from a
retrospective study of 700 patients recently released by Dr. Douglas Dieterich gave indication that the use of oral and
injectable anabolic steroids may be effective in decreasing the potential for
lipodystrophy-associated body habitus changes.[xxx]More study needs to be done to confirm
this trend, though.
Human Growth Hormone (Serostim)
While
the relative ineffectiveness of GH as a muscle-building anabolic hormone is
detailed in later sections, GH does appear to have a role in reducing
lipodystrophy because of its effect on lipid oxidation (fat burning), as was
asserted by a poster presentation from Dr. Gabriel Torres of New York, that was presented at the XII
International Conference on AIDS in Geneva.[xxxi]
It
should be noted that Dr. Torres said that while five patients had partial of
total reduction of fat redistribution on 5 and 6 mg doses of GH, which I assert are overdoses
for most people, four of the patients (80 percent) had either elevated glucose,
elevated pancreatic enzymes, or carpal tunnel syndrome, so GH at these doses
increased the potential for serious health problems. Elevated blood glucose can lead to diabetes and the problems that result including
cardiovascular problems, eye damage, and neuropathy; elevated pancreatic enzymes
can lead to pancreatitis; and carpal tunnel syndrome
is quite painful and may require surgery.
I
suggest that if Serostim GH is implemented, it should be considered that
Serono’s full vial dose is an
overdose and this may be why 5 and 6 mg doses caused these problems. It is
advisable to adjust the dose down for each individual, in an attempt to gain
the benefit without increasing the problems. At this time I have reports of a
reduction of protease belly and other types of lipodystrophy with doses as
low as 1 mg per day and up to 3 mg per day with no side effects. I assert that
lower daily doses are safer than higher doses administered every few days, and
at a correct dose growth hormone can be an important part of the tools that
address the underlying metabolic problem. While growth hormone will have a less
powerful effect at a lower dose, at the proper individual dose there will still
be a significant effect on fat cell metabolism with significantly less
potential for side effects.
Exercise
Exercise,
too, improves insulin sensitivity,[xxxii]
so people with insulin resistance should consider some kind of regular exercise, especially weight-training,
which also builds lean body mass. Aerobic exercise does not build significant
lean body mass. Aerobics may be useful in an effort to reduce lipodystrophy but
if a person is losing lean body mass it should be avoided at least until the
person has regained any lost weight or stabilized. Aerobics will use energy
that the body would normally use for rebuilding lean body mass, only
accelerating the loss of lean body mass. If your weight is stable and not in
danger of losing weight, to optimally burn fat and reduce lipodystrophy I
suggest doing aerobics three times per week on alternate days to
weight training days, first thing in the morning on an empty stomach. (See the
exercise chapter on page 129.)
Nutritional Considerations
Carbohydrates
I
would also suggest altering your diet so that it is balanced somewhat like what
might be called an “evolutionary-type hunter-gatherer diet.” This means getting
more protein and a moderate amount of the healthy types of fats, while eating
fewer high-calorie, starchy, complex carbohydrates or high-glycemic, sugary,
simple carbohydrates.
Currently,
many progressive nutritionists are recommending that people with insulin resistance consider reducing their total
calorie intake and intake of high-calorie complex carbohydrates that can
release into the blood stream quickly,[xxxiii]
including wheat breads and most processed wheat products. These kinds of
carbohydrates actually are quite calorie dense and can upset insulin metabolism
as much as sweets.[xxxiv]
[xxxv]
They are even more problematic when included in high fat foods. (Think pizza
and ice cream.) Also on the list of carbohydrates to avoid is the sugar called
fructose, which is known to promote insulin resistance, and raise cholesterol.[xxxvi]
Look for it on ingredient panels as fructose or high-fructose corn syrup. I
also underline that some people will experience a reduction in insulin
resistance just by reducing the total calories in their diet, as many people
simply eat too many calories. However, if
you are having a hard time maintaining weight because of wasting
 or
infection, getting plenty of healthy calories is essential for keeping and
building lean body mass, so be careful about reducing your intake of food.
At
the same time, I recommend an increase in the intake of complex carbohydrates
sources that contain less total calories but lots of fluid and nutrients, like
vegetables. Compared to grains, vegetables are more nutrient dense, and less
calorie dense. While some glycemic indexes vegetables like potatoes and carrots have
high, they supply good amounts of nutrients per calorie, and they do not
contain a great amount of calories for their volume like grains or sweets do,
so their effect on insulin production, insulin resistance and body fat accumulation is not as great.
(Carrots contain only 195 calories per pound, boiled potatoes contain 450
calories per pound, while breads contain about 1200 to 1500 calories per pound,
and sugar and sweets contain about 1700 calories per pound.)
Other
good carbohydrate sources are beans, yams and green peas, and whole fruits like
oranges, grapes, apples, pears, and cherries. In other words try to eat natural
food carbohydrate sources that are one step away from nature.
If
you do want to include grains in your diet, barley, cream of rye, oatmeal and
brown rice have relatively lower glycemic indexes than most wheat products, but be careful to
moderate the total amount of these high calorie starch sources. If you include
them in your diet, I suggest eating servings that are about one third as much
you’d really like to eat. (Again, try to moderate your total carbohydrate
calories if your goal is to reduce insulin resistance.)
While
a high-carbohydrate diet has been recommended by some nutritionists for
conditions of insulin resistance (diabetes), a study by Chen of Stanford
University, showed that a lower-fat, higher-carbohydrate diet led to higher
day-long blood glucose, insulin, and triglycerides,
as well as post-prandial (after a meal) accumulation of triglycerides, and
increased VLDLs (very low density lipoproteins),[xxxvii] which can increase the risk of
cardiovascular disease. The idea that lower carbohydrates diets are superior is
supported in an article in Nutrition Reviews by dietitian Nancy Sheard, who
said, “Recent studies indicate that a
diet high in monounsaturated fat
 and
low in carbohydrate can produce a more desirable plasma glucose, lipid, and
insulin profile.”
[xxxviii] A study published in the Journal of
the American Medical Association further supported this approach when it showed
significantly elevated triglycerides and LDL cholesterol levels with a high carbohydrate
diet, while a high-monounsaturated fat diet let to a lower-risk lipid profile.[xxxix]
Fats
While
it is also best to reduce any excessive intake of fats, I don’t advocate a very
low-fat diet, but a reduction in excess saturated fats, found in animal fat
products like butter and lard, and excess omega-6 fats, which are found in common vegetable
oils, like corn, safflower, and sunflower oils. Excess saturated fats and
omega-6 fats can promote insulin resistance.115 [xl] [xli] [xlii] At the same time I recommend a
moderate intake of fresh food sources of the essential fatty acid called omega-3, which can reduce insulin
resistance,[xliii] and reduce the potential for
atherosclerosis and heart attacks.[xliv]
[xlv]
Omega-3 fats are found abundantly in cold water fish like salmon, sardines,
tuna, rainbow trout, anchovies, and herring, and in lesser amounts in flax seed
oil, some nuts and seeds and beans, like walnuts, pumpkin seeds and soy beans,
and in much smaller quantities in dark green leafy vegetables. Consider also
including some daily consumption of monounsaturated fats from sources like
olive oil. These too reduce the risk of cardiovascular disease.
Data
also suggests that high saturated fat in the diet promotes more bodyfat
accumulation compared to polyunsaturated fats like omega-3 fats,[xlvi]
[xlvii]
so if you want to be lean, eat clean.
Finally,
avoid eating any food that contain artificial fats or processed fats, like
hydrogenated or partially hydrogenated oils. Partially hydrogenated oils are
found in foods like margarine, french fries, potato chips, shortening, many
baked goods, and mayonnaise. Harvard researchers have found a very strong link
between these types of unhealthy fats and cardiovascular disease.[xlviii]
Protein
HIV
has protein malnutrition as a common theme; a lack of optimal protein
contributes to the loss of lean body mass and trouble maintaining it. To reduce
the loss of lean body mass and to increase it, I suggest that your diet include
extra protein that totals at least 3/4 gram per pound of body weight per day.
If you lift weights, studies of HIV(-) subjects by world-renowned protein
scientist Dr. Peter Lemon show that
you may need a total of at least 0.8 grams of protein per pound of body weight
per day for optimal increases in lean body mass.[xlix]
[l] If
you are not allergic to dairy protein, consider eating cottage cheese as a
“best” protein for building muscle, as it contains a great amount of the amino
acid L-glutamine, which is discussed below.
(Note: dairy allergy can cause diarrhea.)
Also
consider supplementing your food protein with a protein powder drink two or
three times per day. Note that the dairy protein called casein, seen on labels
as calcium caseinate, appears to have the potential to be
somewhat more effective for improving lean body mass than other proteins, like
whey.[li]
The Zone Diet
Although
I do not agree with some of his more dogmatic concepts, my recommendations for
nutrition have some similarities to the “zone” diet outlined in the book Mastering the Zone, by Dr. Barry Sears. While aspects of the zone
diet can be criticized scientifically, I have had numerous reports that the use
of the zone diet has helped people with HIV reduce cholesterol, the potbelly,
triglycerides, and lipodystrophy symptoms, in general.
The Atkins Diet
The
Atkins diet is a very low carbohydrate, high protein, high fat diet that can
decrease bodyfat significantly. I have reports of people successfully using the
Atkins diet to reduce lipodystrophy symptoms. Consider that it is basically
impossible to get the RDA of vitamins, minerals or fiber from this diet, so if
you use it, take strong multi-vitamins and extra fiber, and consider that it
shouldn’t be used long-term. Also be sure to favor monounsaturated and omega-3 fats over omega-6 and saturated fats.
Dietary Supplements
Supplements
that have been shown to improve insulin sensitivity include chromium,[lii]
and I recommend 200 to 400 micrograms (mcg) of chromium three times per day in
the polynicotinate or picolinate form, as one recent (non-HIV) study showed
that 1,000 mcg of chromium per day increased insulin sensitivity by about 40
percent without toxicity.[liii]
The
herb silymarin (milk thistle) as a standardized extract in
a dose of 200 mg three times per day has been shown to be effective in
improving liver function and improving insulin sensitivity.[liv]
There has been talk that silymarin can alter liver function in a way that might
affect the metabolism of protease inhibitors, so it is possible that people who
are taking protease inhibitors should not take silymarin. There is no
conclusive data on this yet.
But
the best supplement for improving insulin sensitivity and glucose disposal may be the antioxidant
called alpha lipoic acid (ALA), at 100 to 300 mg three
times per day.[lv]
In diabetic studies ALA improves insulin dependent and non-insulin dependent
glucose uptake, and it has been shown to effectively lower blood sugar
comparable to insulin itself.[lvi]
I believe this is one very important reason ALA is a must for anyone taking HIV
medications, especially protease inhibitors. HIV-nutrition expert Lark Lands, Ph.D., asserts that ALA is a
must for people with HIV because of its effect on improving glutathione production and recycling.[lvii]
Studies last year at Stanford University showed that glutathione levels
directly correlate with increased survival for people with HIV.[lviii]
As
noted by the late Canadian protein chemist Chester Myers, Ph.D., N-acetyl cysteine
(NAC) can be a valuable addition to the supplements
that address lipodystrophy, because of its effect on improving glutathione, which is necessary for
glucose metabolism. I suggest 500 to 1,000 mg of NAC three times per day.
Also
carnitine, as the prescription version
called Carnitor, would be beneficial in
higher doses, about 500 to 1,000 mg three times per day, as it helps to lower
triglycerides,[lix]
which are generally elevated when lipodystrophy is present. Note that the
acetyl-L-carnitine form of carnitine may be more effective than
plain carnitine, but it is more expensive.
Also worth
considering is the omega-3 dietary supplement called EPA (fish oil), which has been shown to reduce
insulin resistance,115 and lower triglycerides somewhat in a study
with HIV(+) men.[lx]
And
taking a strong multivitamin, multimineral supplement that includes chromium, vitamins A, D, E and calcium and magnesium will help improve insulin sensitivity.[lxi] [lxii]
[lxiii]
[lxiv]
[lxv] [lxvi]
I recommend taking a supplement that contains doses that are much higher than
the RDAs, though, as numerous studies have shown that higher nutrient levels
are required in HIV disease.[lxvii] [lxviii]
Finally,
high dose biotin supplementation is frequently prescribed by
nutritionally-oriented medical doctors to improve glucose metabolism in
diabetes.[lxix]
[lxx]
High dose biotin is also known to improve diabetic neuropathy.[lxxi]
The dose of biotin that is commonly used is 1,000 mcg three times per day.

Cardiovascular Disease

As I
mentioned in the beginning of this article, we are also beginning to see
cardiovascular disease in people on protease inhibitors. When cardiovascular
disease is a consideration, we want to make sure that specific preventive
nutrients are included. While there are many that can be included for this
purpose, to keep it simple I suggest the following: vitamin E at 400 to 800 IU
three times per day to reduce the potential for oxidation of blood fats that
can contribute to atherosclerosis;[lxxii]
vitamin C at 1,000 to 2,000 mg three times per day to assist vitamin E in
reducing blood fat oxidation;[lxxiii]
folic acid at 800 mcg three times per day to reduce the
potential for elevated homocysteine, which appears to be another
major contributory factor to cardiovascular disease.[lxxiv]
[lxxv]
It should also be noted that vitamins B6 at 50 mg three times per day and
vitamin B12 at 100 to 500 mcg three times per day help to reduce homocysteine.
Of course, all HIV(+) people should consider taking high doses of supplemental
B vitamins, as studies by Dr. Marianna Baum, of the University of Miami, showed
that HIV(+) people frequently require 6 to 25 times the RDA of these essential
nutrients to stay healthy.139 140

Glutamine

For
any loss of muscle, Judy Shabert,
M.D., M.P.H., R.D., asserts that supplementing with high doses of the amino
acid L-glutamine, will help reduce the
catabolic process of breaking down muscle tissue,[lxxvi]
and a recent study of wasting HIV patients by Prang showed that this might be true. (See Dr.
Shabert’s article in the August 1997 issue of POZ magazine.) For frank wasting,
HIV(+) people are using between 12 and 36 grams per day of L-glutamine. (One
tablespoon is 12 grams.) I have friends who have halted their random diarrhea and improved their lean body mass using these
kinds of L-glutamine doses, and in Prang’s study wasting and diarrhea and were
checked by using 30 to 40 grams of glutamine per day. Glutamine too, has been
shown to have a powerful effect on improving glutathione production,[lxxvii]
and glutamine improves insulin sensitivity.[lxxviii]
[lxxix]
If
you are losing weight I suggest that you supplement your diet with a tablespoon
of L-glutamine added to each serving of supplemental protein
two or three times per day between meals. If your weight is stable, L-glutamine
may be supplemented at lower doses, such as one or more teaspoons per day.
(Important
note: most dietary supplements only stay in the blood for a few hours, so it is
wise to take them several times per day.)
Metformin (Glucophage)
Realize
that while taking dietary supplements, especially alpha lipoic acid, may help,
it is wise to investigate the use of the drugs that are prescribed to improve insulin sensitivity. Ask your doctor about these
drugs, which include metformin.[lxxx] New data presented by Saint-Marc at
the 6th Retrovirus Conference, in February, 1999 indicates that metformin may
decrease visceral fat while decreasing blood glucose, insulin, and lipid levels. 102 Serostim can increase blood glucose, insulin and
insulin resistance.[lxxxi] [lxxxii] This means that metformin might be
found to be superior to Serostim growth hormone because it not only addresses
fat redistribution, but reduces some of the underlying metabolic problems that
growth hormone can promote. An important consideration is that while 6 mg per
day of Serostim is priced at about $6,000 per month, which makes it
inaccessible for a majority of people who have lipodystrophy, metformin is
available with a doctor’s prescription at any pharmacy, and if a person has to
pay for it themselves. Realize that while taking dietary supplements,
especially alpha lipoic acid, may help, it is wise to investigate the use of
the drugs that are prescribed to improve insulin sensitivity. Ask your doctor
about these drugs, which include metformin.152 New data presented by Saint-Marc at the 6th
Retrovirus Conference, in February, 1999 indicates that metformin may decrease
visceral fat while decreasing blood glucose, insulin, and lipid levels.102 Serostim can increase blood glucose, insulin
and insulin resistance.153 154  This
means that metformin might be found to be superior to Serostim growth hormone
because it not only addresses fat redistribution, but reduces some of the
underlying metabolic problems that growth hormone can promote. An important
consideration is that while Serostim is priced at $6,000 per month, which makes
it inaccessible for a majority of people who have lipodystrophy, metformin is
available with a doctor’s prescription at any pharmacy, and if a person has to
pay for it themselves, it only costs about $35 per month.
However,
cautions about the use of metformin are warranted. Dr. Michael Dube, of the University of
Southern California at Los Angeles says, “Lactic
acidosis
 is a
rare side effect of metformin that is more likely to occur when there is some
impairment of kidney function. Lactic acidosis, which can be fatal, is also a
rare side effect of use of nucleoside analogs. There is no way to know at this
time if using the two together might result in more frequent, or more severe
lactic acidosis problems. In my opinion anyway, metformin and NRTI’s therefore
should only be used together with great caution. Also, keep in mind that
metformin can lower vitamin B12 levels.”
I
should also note that some people are finding that switching antivirals causes
a marked reduction in some lipodystrophy symptoms. This is an area that is
currently receiving a considerable amount of study. 
For a good
and simple brochure on lipodystrophy, visit http://www.vhconcepts.com/pdfs/2002.changes.pdf
. For an update of lipodystrophy issues go to www.medibolics.com , www.powerusa.org and subscribe to
Nelson’s free email list by sending a blank email to pozhealth-subscribe@yahoogroups.com

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Update on Egrifta for the reduction of visceral fat accumulation associated with HIV lpodystrophy

Serono launched Egrifta this month.
Doctors are calling in the number included in the link below to get the paper work started for insurance reimbursement.
It seems that some insurance companies are  already starting to pay for it, but high copays may be required. Serono has a $200 copay assistance per prescription.
The total yearly cost is $23,900.   It is injected once a day under the skin (2 mg).  After 26 weeks, some people lose anywhere from 15 to 25 % (avg 18%). You will regain the fat if you stop using i.
I encouraged Serono to fund studies with exercise and the use of Metformin, two approaches that may enhance fat loss.
They could not tell me if any Medicare Part D program has already paid for drug yet.  There is no copay assistance for Medicare Part D patients due to a federal law that prohibits them.
The patient assistance program provides free drug to people with incomes lower than 6 times the poverty level ( around $68,000 per year for a single person with no dependents). Your doctor has to contact them, per the following link:
I encourage that people on this list try to apply for the patient assistance program. The Fair Pricing Coalition ( a group of activists that I am part of) needs to find out if there are any problems in applying for this program, so please help us audit it and report to this list.
More info in Egrifta.com

FDA Committee Unanimously Recommends Egrifta for Lipodystrophy

FROM POZ.COM

May 27, 2010
FDA Committee Unanimously Recommends Egrifta for Lipodystrophy

A U.S. Food and Drug Administration (FDA) advisory committee has unanimously recommended that Egrifta (tesamorelin), Montreal-based Theratechnologies’ experimental product for the treatment of excess abdominal fat in HIV-positive people with lipodystrophy, be approved by the agency.  Though the FDA is not required to follow the recommendations of its advisory committees, it usually does so.

Several of the 16 panelists making up the Endocrinologic and Metabolic Drugs Advisory Committee, which met May 27 at the University of Maryland University College (UMUC) Marriott Conference Centers in Adelphi, Maryland, stressed that there is a need for additional follow-up studies to monitor the long-term safety and efficacy of the drug.

Egrifta is a synthetic human growth hormone-releasing factor. Phase III clinical trials of the drug indicate that it decreases visceral adipose tissue (VAT)—fat deep within the belly—by about 17 percent.

According to Christian Marsolais, MD, vice president of clinical research and medical affairs at Theratechnologies, who reviewed the Phase III efficacy results at today’s hearing, 57.4 percent of patients taking Egrifta experienced an 8 percent or greater reduction in VAT—the primary goals of the studies—compared with 29.3 percent of the placebo group.

Unlike Serostim (recombinant human growth hormone), an earlier contender for treating excess VAT, Egrifta has long been suggested to have fewer side effects when used for at least a year, including a minimal effect on blood sugar (glucose) levels.

There were, however, conflicting reports at today’s hearing regarding the risk of diabetes in people receiving Egrifta in the Phase III clinical trials.

Graziella Soulban, MD, director of clinical research at Theratechnologies, reported higher rates of pre-diabetes and diabetes among those receiving Egrifta, compared with placebo, during the first 26 weeks of the studies. But between weeks 26 and 52 of the studies, however, the number of people with glucose intolerance and diabetes dropped. 

Ali Mohamadi, MD, a clinical reviewer from the FDA, unveiled a slightly more detailed analysis. According to the FDA safety analysis reported this morning, 49.2 percent of patients receiving Egrifta had no instances of raised blood-glucose levels. However, 17.3 percent of those receiving Egfrifta had three or more increased blood-glucose measurements during the clinical trial, compared with 7.3 percent of those receiving placebo.

Mohamadi also reported that 25 percent of patients in the tesamorelin group who started off as pre-diabetic eventually went on to develop frank diabetes in the studies. Among those who began treatment without a history of diabetes and had normal glucose levels, Mohamadi confirmed, the risk of diabetes during the study remains low.

Increases in insulin-like growth factor 1, or IGF-1, was another safety issue discussed at length during today’s meeting. Though increases in IGF-1 are considered to be an indicator of Egrifta’s activity, IGF-1 has also been suggested to promote tumor growth, which can be problematic in a population of individuals—including people living with HIV—who already face a higher risk of cancer. According to Mohamadi, a third of patients receiving Egrifta had significantly elevated IGF-1 levels. However, according to Soulban, these increases were not found to be associated with an increased risk of any type of cancer in the 52-week Phase III studies.

Mohamadi reiterated that decreases in decreases in VAT associated with the use of Egrifta have not been shown to decrease the risk of cardiovascular disease—an important potential benefit of any drug that treats abdominal obesity—and several panelists reiterated that future studies should explore this goal. And though the panelists were divided on the data submitted to the FDA regarding improvements in body image and body perception in the studies, many were clearly impressed by the mid-day public testimony offered by three people living with HIV—Jeff Berry of the AIDS Treatment Activists Coalition and two Egrifta clinical trial participants—who emphasized the detrimental effects of lipodystrophy in people living with HIV.

As the clock approached 4 p.m., the final vote was cast by the advisory committee members, in response to a single question put forth by the FDA: Does the risk-benefit assessment support approval of Egrifta? Sixteen voted “yes”—there were zero “no” votes and no abstentions.

Several panelists stressed that follow-up data should be collected to better understand the long-term risks of glucose abnormalities and IGF-1 increases. Theratechnologies noted that it is already planning a safety monitoring program that will go into effect if the FDA agrees with the advisory committee panel and approves the drug for use in the United States.

A final decision from the FDA is expected within the next two months. The agency has until July 27 to notify Theratechnologies of the drug’s approval status and of any post-marketing studies that must be conducted.

An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults

I bet this could compete with Theratecnologies/Serono’s Tesamorelin eventually. But Merck is smart going after baby aging boomers

An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults
ScienceDaily (Nov. 5, 2008) — Researchers at the University of Virginia Health System report that a daily single oral dose of an investigational drug, MK-677, increased muscle mass in the arms and legs of healthy older adults without serious side effects, suggesting that it may prove safe and effective in reducing age-related frailty.

Published in the November 4, 2008 issue of Annals of Internal Medicine, the study showed that levels of growth hormone (GH) and of insulin-like growth factor I (IGF- I) in seniors who took MK-677 increased to those found in healthy young adults. The drug restored 20 percent of muscle mass loss associated with normal aging.

“Our study opens the door to the possibility of developing treatments that avert the frailty of aging,” explains Dr. Michael O. Thorner, a nationally recognized researcher of growth hormone regulation and a professor of internal medicine and neurosurgery at UVA. “The search for anti-frailty medications has become increasingly important because the average American is expected to live into his or her 80s, and most seniors want to stay strong enough to remain independent as they age.”

Funded by the National Institutes of Health, the two-year, double-blind, placebo-controlled, modified-crossover study involved 65 men and women ranging in age from 60 to 81.

The study drug, MK-677, mimics the action of ghrelin, a peptide that stimulates the growth hormone secretagogue receptor (GHSR). Drug developers are focusing on GHSR because it plays an important role in the regulation of growth hormone and appetite. They think it may prove to be an excellent treatment target for metabolic disorders such as those related to body weight and body composition.

According to Dr. Thorner, the UVA research was a “proof-of-concept” study that sets the stage for a larger and longer clinical trial to determine whether MK-677 is effective in people who are frail and to assess its long term safety.

——————————————————————————–

University of Virginia Health System (2008, November 5). An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults. ScienceDaily. Retrieved November 10, 2008, from http://www.sciencedaily.com /releases/2008/11/081104132902.htm