Just found this.. really interesting.. Sorry guys. threadjacking.com lol Too interested in IGF-1 now and hair loss..
Truth is that Accutane is a bit of a paradox. It actually INCREASES Insulin Resistance while on treatment, but the effects usually disappear afterwards.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11747145&dopt=Abstract While on treatment you can get High LDL levels, poor glucose disposal rates, increased Insulin Secretion, and low SHBG. Wow, it seems to go against everything that we are trying to accomplish (clear skin) by going on these diets and medications etc.
On the other hand, Accutane still treats acne, but the effects are only during treatment (supposedly). Anyway, apparently it does so because the effects of 13-cis-retinoic acid (causes the above) possibly overrides certain aspects of IR, so that it can still inhibit DHT conversion in the sebaceous follicles, decrease sebum production, and slow skin cell shedding, etc. Therefore, it does still work positively along the hormonal aspect of the Insulin Resistance pathway. Meanwhile, Roche hasn't entirely figured this out and that's OK because
there are several articles out there that explain WHY:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11880314&dopt=Abstract (nothing to do with acne but proves that retinoic acid increases IGFBPs)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9064277&dopt=Abstract (vit. A and it's role)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11404231&dopt=Abstract (proves that it depends on the form of Vitamin A as to whether a certain type of IGFBP hormone will be increased).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7518821&dopt=Abstract ( I think this is also a good one to read)
Of course, if you can't understand that, then this is my version of how Acne, Insulin Resistance, & Accutane all tie together:
OK, so you're at lunch and you eat something, lets say a SANDWHICH (meat, vegetables, grain bread), and it enters your digestive system where it's broken down. Now, depending on it's glycemic load, a certain amount of glucose will be available for your body's energy needs. This prescence of glucose will cause your pancreas to produce insulin to enhance glucose utilization and sometimes it will be a HUGE amount of insulin! Insulin works by binding to insulin cell receptors to allow glucose to pass through the cell. Now, if your body (cells, tissues) doesn't need the glucose, it will be converted into glycogen and fat for storage in your liver, skeletal muscle, adipose tissue, and skin.
Now, if your liver can NOT store the glycogen & fat and your cells & tissues will not accept the glucose then you have a problem. This is known as Insulin Resistance, which can later lead to Type I Diabetes (don't make enough or ANY insulin), Type II Diabetes (unable to use the insulin you do make), Heart Disease (due to high LDL cholesterol levels, free fatty acids), Hypertension, Dyslipidemia (lipid imbalance in blood stream), Obesity etc. all prevalant in most Western societies. So anyway, IR occurs because your cells are either too full of glucose or they don't RECOGNIZE the insulin you do have. As a result, you not only have all this extra insulin, but glucose, free fatty acids & amino acids floating around in your blood stream with no where to go....
Now, some of us do not have the same gene defects (read middle of article on CYP450 for specifics). Therefore the PATHWAY to this next part, is different for all of us depending on what our defect, or in other words, hormonal disorder is. Examples of hormonal disorders with acne as a POSSIBLE Symptom are Hypothyroidism, Hyperadrenalism, Insulin Resistance, Polycystic Ovarian Syndrome (PCOS)-Syndrome X, Hyperandrogenism, Congenital Adrenal Hyperplasia (CAH), Hypercortisolism - Cushings Syndrome, etc.
So depending on the pathway, this extra or free insulin is going to cause your Adrenal Glands and Ovaries OR Testicles to produce the followingSteriod Hormones: Estrodial, Estrone, Progesterone, Testosterone, Androstenediol, DHT (5-alpha-dihydrotesterone) and DHEA (Dihydroepiandrosterone). These hormones in excess or in deficiency create your...hormonal imbalance.
Obviously, if it's in excess you know why you have the problem, but what about if you are deficient in a hormone (vitamin, enzyme, etc) right? What happens is that your body is looking for this hormone and if it can't find it, and is capable of making it, will produce MORE. At least it thinks it's producing more, but sometimes it's unable to produce the hormone and as a result, OTHER hormones get overproducedin the process.
The same thing applies to IR, if your cells don't recognize the presence of insulin (can't bind to cells), then your body keeps making more insulin, "thinking" that you don't have enough in your system. Unfortunately, it doesn't matter how much your body produces or tries to produce of a hormone, because there is a problem in the pathway that makes this mechanism work perfectly. Therefore, until the defective pathway is FIXED, the viscious cycle will continue...or get worse (burnout, tumors, cancer).
One of the results of this would be testosterone conversion into DHT (a super androgen) in your blood stream and in your sebaceous glands & hair follicles. There are several enzymes responsible for this conversion such as, 5-alpha reductase, 3-alpha-hydroxysteroid dehydrogenase, and 3-beta-hydroxysteroid dehydrogenase. As a result of DHT conversion, there's an increase production of sebum, skin cell proliferation, inflammation, etc. all thought to contribute to the production of acne in SUSCEPTIBLE individuals.
Does any of the above sound familar? Well it should considering that by now we should have learned that during Puberty, we ALL go through a state of INSULIN RESISTANCE! The only way our tissues can grow is if they become insulin resistant (IR). Therefore, IR increases the proliferation of not just tissue cells, but skin cells, etc. Now through your DIET you will accquire or overproduce IGF-1 (Insulin-like Growth Factor) and Insulin, both of which increase our male hormones. However they do this because we have DECREASED levels of IGFBP-3 (Insulin-like Growth Factor Binding Protien) and SHBG (Sex Hormone Binding Globulin). Both of which bind steriod hormones and growth factors that are responsible for the production of acne and certain other hormonal & health (cancer, tumors) problems.
Now, this is the pathway to which Accutane (13-cis retinoic acid) works. It increases your IGFBP-3 hormone which prevents IGF-1 from binding to the androgen receptors. In turn, this prevents the production of Androgen which means a decrease in the amount of DHT (5alpha-dihydrotestoterone) that will be converted in the sebaceous follicles. Furthemore, it also DIRECTLY prevents the conversion of DHT by inhibiting the enzyme (3alpha-hydroxysteroid dehydrogenase) neccessary for this function.
So Vitamin A, Natural Accutane (program by which you create your own 13-cis retinoic acid), and Accutane are going to attack acne by INCREASING IGFBP-3. Which prevents IGF-1 from binding to androgen receptors, decreases androgen production, DHT conversion, skin cell proliferation, and sebum production. While various other medications, supplements (like the popular B5) and also various DIETs are going to attack acne along other Insulin Resistance pathways.
So if we continue discussing diet, then by avoiding certain problematic foods for YOU, like High Glycemic Load Carbohydrates, etc you can naturally INCREASE SHBG and IGFBP-3. Now, we already know what IGFBP-3 does by reading the above articles, and SHBG works by having a higher affinity to binding male hormones over female hormones in your system. In fact, in the presence of Estrogen (birth control pills), SHBG will be further synthesized in the liver, but in the presence of Insulin, it won't be produced and Obesity, Acne, Hirusitism, PCOS, Hypothyroidism, ovarian tumors, and enlarged prostates, and gigantisism can result.
Furthermore, just by lowering or balancing your insulin levels which HAVE been done through dietary changes and/or medications/supplements, you will also prevent the conversion of DHT by inhibiting enzyme (5-alpha reductase and 3-beta hydroxysteriod dehydrogenase) function, skin cell proliferation, inflammation, and sebum production. However, not everyone notes a complete decrease in sebum production, despite dramatic improvements in clarity. Which indicates that sebum production isn't neccessarily NEEDED to have acne. If you think about people with dry skin with acne and others with ingrown hairs, the problem isn't sebum but skin cell proliferation, poor exfoilation, and inflammation, right?
Of course that aspect can be controlled or prevented, topically anyway, by following a regimen similar to the "Acne Cure" I've been doing the Acne Cure for years now and I didn't even know it...lol. Using (gentle) acids and exfoliants on your skin is great way to help unglue the clogged pores (sebum helps here), and encourages faster skin cell turnover & shedding. Not to mention, taking certain vitamins will also enourage faster healing and skin cell sheddingwhich I guess is what makes an acne sufferer's skin different from someone that happens to just have "Oily" skin.
Now, I would like to clarify once and for all (LOL) that we don't all experience the same SYMPTOMS and that is also why Diabetics (type 2) and kids going through PUBERTY (medically defined state of Insulin Resistance)don't ALL get acne, hirsutism, etc. Symptoms can be external or internal and they vary WIDELY depending on what ENZYME/GENE is defective (usually somewhere on a CYP450 gene [link=drnelson.utmem.edu/P450lect.html]drnelson.utmem.edu/P450lect.html[/link] ) and they could occur at the age of 10 or possibly catch up to you in late adulthood. I guess that's what makes people feel safe and comfortable to do whatever they please DESPITE the scientific evidence behind it all.
For example, did you know that Insulin Resistance is not only genetic but can also simply be passed on if the Mother is in an state of Insulin Resitance during pregnancy? Perhaps that's why some kids have terrible problems that their parents didn't have. Of course, the research wasn't there 50, or even 30 years ago, but it is here now! So in terms of general good health, that right there is the reason we should be getting the Willett's Food Pyramid in 2004. Yes, thankfully, they have admitted that the USDA Food Pyramid was not based on much scientic research and may be the reason behind increasing Obesity and Diabetes rates.
Therefore, I understand one's skepticism and distrust, but you've got to learn to research and connect the dots for yourselves. For when you do, you'll discover that while there are MANY different ways to attack acne, there are also treatments in existence that are SAFE & effective, but were never fully publicized (like topical spironolactone)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2972662&dopt=Abstract and
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2150020&dopt=Abstract . Nevertheless, the majority of the topicals, medications, supplements (like B5), dietary changes (allergic or not), and alternative methods (meditation, exercise, etc) b]all work on some hormonal level[/b]. As such, they are all attempting to either fix your homonal imbalance by Controlling your Insulin, by preventing the Conversion of DHT in sebaceous follicles, by preventing the proliferation of skin cells, or by reducing your free testosterone/androgen in the blood stream, etc. ALL of which could be caused by a lack of Insulin sensitivity or Insulin Resistance.
So once again, prolonged hormonal imbalances are due to some sort of lack of an enzyme, which explains why SOME people cleared when taking Probiotics, Digestive Enzymes or doing Liver Cleanses & Detoxes. Not to mention, that since most of us use treatments ranging from topical anti-androgens to Internal Anti-androgen medications, supplements, diets or exercise programs we have found ways to reduce, control or ELIMINATE acne (and other hormonal problems). Therefore, you must analyze your body's own "blue print" and depending on YOUR own external and/or internal factors and [/b]personal sensitivty level[/b], you may need to use one or ALL of these methods to solve your problems.
Also, I am not ALWAYS entirely for dietary changes only. Not everyone HAS to do that. I believe that many factors (Environmental, External, Internal-Mental) are involved with acne and just because one is irrelevant to you, doesn't mean that it is for someone else. Unfortunately because there are NUMEROUS choices out here, at some point we have ALL chosen the wrong ones. The truth is, whether some of you like it or not, certain methods work BEST for certain people. Hence, one must know their body and understand just what hormones & enzymes are involved in causing THEIR problems. Once they do that, it is easier to find a treament (natural or traditional) that will be more effective than anything they've done before. Unless of coure they simply GROW OUT OF IT, as I'm more often wondering is the case with Accutane...
If you don't know what is wrong inside, then you should discuss your problems & "symptoms" with your doctor so that you can be referred to a Gastroenterologist, Endocrinologist, Allergist, Nutritionist, Naturopath, or some other Specialist that will help you find out. For most of you this is, thankfully, only puberty (still suxs), but for others this can continue for several decades. While I know some of you tend to worry & overdo things, thanks to the angst acne can put us in, please note that it's impossible to eliminate ALL DHT or ALL sugar from your system and still function (normally). Therefore, when trying to find the connection for yourself, PLEASE don't obsess over avoiding every possible problematic food or give up too quickly. Remember, we are all different and our bodies will decide when we've done the RIGHT things, not us ;-) So, the sooner you find out the truth for you, the less hormonal and health problems you may have to deal with in the future.
Oh and one more thing, the reason it's Important to know how Accutane, the "greatest discovery for acne in the past 30 years," they say, works, is because now we know how to implement this for ourselves. Now that we know how it relates to diet, we can take that information and find a way to increase those chemicals "naturally." So instead of orally taking 13-cis-retinoic acid or finding a natural way to convert this in our system, we can jump straight into what's REALLY doing the job. Remember, Accutane inhibits the actions of IGF-1 by INCREASING IGFBP-3! We already know that we can accomplish this through diet as well. Therefore, we need to eat right, take the right supplements, or find some miracle pill that will effectively increase IGFBP-3 at a safe level for us. Then we have the acne controlling effects of accutane, only permanently and hopefully without any negative side effects.
IGF-1: Is It the Real Deal?
February 3, 2010 by Jerry Brainum
Insulinlike growth factor-1 is so named because of its resemblance to insulin. It consists of 70 bonded amino acids, which makes it a protein-peptide hormone. That means that like growth hormone, IGF-1 must be injected. Otherwise it degrades in the gut, rendering it useless.
IGF-1 is considered the key to growth hormone’s anabolic effects, and GH release promotes its synthesis in the liver. The liver also synthesizes six binding proteins that work with IGF-1, with one, IGFBP-3, being the primary IGF-1-bonding protein in the blood. A substance called the acid-labile subunit prevents the premature degradation of IGF-1. The complex of IGF-1, binding protein and the acid-labile subunit extend the time that IGF-1 lasts in the blood to 15 hours or more—compared to the 10 minutes that unbound IGF-1 lasts.
Because IGF-1 is so similar to insulin, it can interact with insulin cell receptors and produce some of the same effects as insulin. In fact, the primary side effect of both excess insulin and IGF-1 is hypoglycemia, or low blood glucose, although insulin is 10 times more potent than IGF-1 in that effect. When you train for an extended time—more than one hour—the liver upgrades its release of IGF-binding protein 3 to prevent the onset of hypoglycemia that would otherwise ensue because of the increased release of IGF-1. IGF-1 also amplifies the action of insulin, even at low doses.
Insulin helps maintain blood IGF-1 by boosting the synthesis of IGFBP-3.
The next challenge was to manipulate endocrine functions at the GH/IGF-1 Axis to override the negative feedback inhibition of IGFBP-3 (Insulin-Like Binding Growth Factor Protein-3) to supercede the narrow physiological range and achieve the maximum IGF-1 output threshold. Approximately 98% of IGF-1 is typically bound to one of 6 binding proteins (IGFBP). IGFBP-3, the most abundant protein, accounts for 80% of all IGF binding. This means that most of the IGF-1 that you produce is bound to IGFBP-3 and not able to bind to specific IGF-1 receptors present on muscle cells and carry out its anabolic actions.
To overcome this MuscleMeds researchers found that there was a direct correlation between TSH (Thyroid Stimulating Hormone) and IGFBP-3. (Insulin-Like Binding Growth Factor Protein-3)
Occurrence of the male hair pattern is considered to be an
androgen-mediated process that depends on circulating testosterone and
dihydrotestosterone concentrations as well as on local conversion of
circulating testosterone to dihydrotestosterone in the skin (catalyzed
by the enzyme 5alpha-reductase). Our data confirm that there is a
stronger link between circulating testosterone and baldness, whereas
testosterone has a less obvious function in regulating the relatively
less androgen-dependent chest hair density. Androgen action stimulates
vellus hair to develop into coarse, pigmented hair on the body, but
prolonged exposure to androgen leads to regression to vellus hair and,
frequently, balding of the scalp. Little is known about the specific
function of SHBG or estradiol in male hair growth or hair loss, and
the results of our study, in this respect, must be replicated before a
credible conclusion can be reached. It is conceivable, however, that
high SHBG levels reduce the bioavailability of testosterone and thus
modulate its effect on hair patterning.
Our findings suggest that high levels of IGF-1 may be associated with
increased risk of vertex baldness. Substantial clinical evidence
appears to support this finding. The efficacy of testosterone
treatment on hair growth in children with hypopituitarism is enhanced
by GH, the effect of which is largely mediated through IGF-1. In
adults with hypogonadism, a combination of GH and gonadotropin
treatment improves testosterone secretion and reproductive function.
It has also been recently reported that GH treatment of GH-deficient
men increases hair scores in androgen-dependent areas. These effects
can be explained either by IGF-1 directly stimulating the androgen
receptor, or by IGF-1 increasing local 5alpha-reductase activity and
thus stimulating the local conversion of testosterone to
dihydrotestosterone. It has been postulated that IGF-1 modifies
post-receptor effectors of the androgen receptor, but this is not
clearly established.
[…]
In conclusion, we have found evidence that high levels of testosterone
and IGF-1 increase the likelihood of vertex baldness, whereas neither
of these hormones appears significantly or suggestively associated
with chest hair growth. SHBG is inversely associated with vertex
baldness as well as with chest hair growth, although the association
is significant only with respect to the latter. It appears that the
effect of SHBG, if genuine, could be explained by the involvement of
this compound in the modulation of bioavailability of testosterone.â€
Hormones and hair patterning in men: A role for insulin-like growth
factor 1?
Lisa B. Signorello, Joanne Wuub, Chung-cheng Hsiehb, Anastasia
Tzonouc, Dimitrios Trichopoulos, Christos S. Mantzoros
Journal of the American Academy of Dermatology
Volume 40 • Number 2 • February 1999
Copyright 1999 American Academy of Dermatology, Inc.
“We observed that middle-aged and elderly men who reported modest to
substantial vertex balding at age 45 have lower circulating levels of
IGFBP-3 and higher levels of IGF-1 when controlling for IGFBP-3 level.
Growth factors are beginning to emerge as contributors to hair growth
and loss. IGF-1 is an abundant endocrine, paracrine, and autocrine
growth control factor that promotes proliferative activity in
epithelial and mesenchymal cells in numerous organ systems, including
the hair organ.â€
[…]
“In the hair organ, IGF-1 is produced by connective tissue
constituents,10 and IGF-1 gene expression is enhanced by androgens.11
In androgen-responsive tissue, IGF-1 may act locally to positively
mediate the induction of 5-reductase by dihydrotestosterone.12 This
action of IGF-1 may be consequential for the development of balding
because conversion of testosterone to dihydrotestosterone in the scalp
by 5-reductase type 2 is essential for androgenetic alopecia.13
Indeed, oral 5-reductase type 2 inhibitors are now used to prevent
further hair loss and to induce hair regrowth in men with male pattern
balding.13 Experimental administration of the 5-reductase type 2
inhibitor finasteride results in diminished expression of IGF-1 and
its receptor and enhanced expression of IGFBP-3 in the rat prostate,
an androgen-dependent tissue.14 IGFBP-3 is the major carrier protein
that modulates the bioavailability of IGF-115 and thus may also be a
regulator of mediators of hair growth and cycle control. Our findings
are compatible with both the direct association of IGF-1 and the
modulating effect of IGFBP-3 on male pattern balding.â€
