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Old 08-10-2003, 07:48 PM   #1
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Post The ACCUTANE - DIET connection

Ok, well I originally goofed on my initial Accutane, Insulin, Puberty post [url="http://www.healthboards.com/ubb/Forum1/HTML/016428.html"]http://www.healthboards.com/ubb/Forum1/HTML/016428.html[/url] , but I am now about to correct that. ;-)

Truth is that Accutane is a bit of a paradox. It actually INCREASES Insulin Resistance while on treatment, but the effects usually disappear afterwards. [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=11747145&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11747145&dopt=Abstract[/url] 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: [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=11880314&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11880314&dopt=Abstract[/url] (nothing to do with acne but proves that retinoic acid increases IGFBPs) [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=9064277&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9064277&dopt=Abstract[/url] (vit. A and it's role) [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=11404231&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list _uids=11404231&dopt=Abstract[/url] (proves that it depends on the form of Vitamin A as to whether a certain type of IGFBP hormone will be increased). [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=7518821&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7518821&dopt=Abstract[/url] ( 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) [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=2972662&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2972662&dopt=Abstract[/url] and [url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_u ids=2150020&dopt=Abstract"]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2150020&dopt=Abstract[/url] . 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. Whadda you think? ;-)




[This message has been edited by SweetJade1 (edited 08-10-2003).]

 
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Old 08-10-2003, 07:57 PM   #2
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sounds good. you don't by any chance know how to increase IGFBP-3 do you? sign me on!

 
Old 08-10-2003, 09:02 PM   #3
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You know, I know of various anti-androgens and other hormonal balancers. Some are prescriptions, supplements, or are based on your diet. In this case we want to increase IGFBP-3 becaue it will reduce IGF-1. Well, so far I know that through dietary changes you can not only increase IGFBP-3 (captures IGF-1) but also SHBG (captures free steriod hormones).

Surprisingly, EXCESS protein, carbohydrates, saturated fats, and Dairy products will increase your levels of IGF-1 and decrease your levels of IGFBP-3 and SHBG. Therefore, that would explain why acne sufferers that correctly altered their diets greatly improved or cleared, even though they didn't eliminate the same exact foods.

Now as to how else to increase IGFBP-3, I don't know. I know that you can also do this through accutane, and Vitamin A, but outside of diet, I am currently unaware (but looking). Although, there are still several ways we can get at the androgen issue that causes our problems.

IGFBP-3 is what is needed to prevent IGF-1 because it used to increase your androgen levels. So you can actually stop the process of having extra androgens with SHBG. This can be increased not only through a healthy diet but also....estrogen. Um, but I guess that is actually more important for us women to know ;-)

So the next possibility is to just plain old inhibit the conversion of DHT (last minute approach). We do this by stopping certain enzymes from producing this form of super testosterone. This is actually the more popular method that all of us are familar with and has produced a variety of anti-androgenic treatments. From Accutane, to RetinA, to Spironolactone, to Diet, this is one of the reasons why they help reduce or eliminate acne.

Hope that helped you some. If you are interested in other antiandrogens, I'll post some for you later =)

 
Old 08-10-2003, 09:14 PM   #4
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Hi!sweetJade, nice and interesting article, a bit long though, lol. Do you know if i can go to doctor or endocrinologist and ask them to perfomr a test for checking my levels of IGFBP or SHBG. I want to know if there are tests like these so i can find out what exactly is causing this flareup.

 
Old 08-10-2003, 11:19 PM   #5
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Great job with all the info ...i think my head would explode for trying to find all that and put it together. we need more people to study like this, i really think some of us do more research on acne than any dermatologist or scientist in the entire world. I heard that not even the people who make accutane know exactly how it works...

 
Old 08-11-2003, 07:01 AM   #6
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Looks like I better eat lunch before I start to read all this, but I definately will!

 
Old 08-11-2003, 08:48 AM   #7
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Sweet Jade, you're awesome. If I remember correctly, you are doing a lot of this research for college (??) and possibly going into the career of nutritionalist or ??? I hope that you do, I wish that the doctors that I've been to understood 1/2 of what you've figured out!

 
Old 08-11-2003, 09:39 PM   #8
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Knut and Boardguy,
LOL, that actually did happen a few times. Of course once my head started to hurt, I either did what T-Zone did or just took a nap. ;-)
Some of this research was due to having to do papers for school, but since I'm not doing that anymore, it's really out of the sheer fun of helping all of you out or to see if I can answer some of these many & mysterious questions.

Faisaljawed007,
Since studies were performed and they were measuring the levels of IGFBP-3 and SHBG, I'm certain there are tests out there. Now as to whether your regular doctor or even an Endocrinologist will test you for these, I don't know. Looking back at my old test results, neither of these were looked at, but there were plenty of other hormones & enzymes they did look at.

There's definately more than one way to find out if you have a hormonal imbalance. Those are just one aspect, but the best way would just be to go see an Endocrinologist and have he or she run some tests on you. Here's a link I posted awhile back that shows the kinds of hormones they'll look at:


 
Old 08-11-2003, 09:49 PM   #9
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Ooops, that link doesn't exist anymore, so here it is:

This will help you know what tests to ask for, TSH, Thyroxine, cortisol, DHEA and other steroid hormones... Unfortunately I don't have ALL my test results so I can't give you the levels for Free & Total Testosterone, Androstenedione, Dehydroepiandrosterone (DHEA) and other hormones. Although, I took a Female Check hormone analysis by Body Balance and it does give me the normal saliva (free?) levels of estrogen, progesterone, and testosterone when you are at days 20-23 of your cycle. Those are:

Body Balance (Great Smokies Diagnostic Labs)
Estrodial: 5.50 - 13.20 pmol/L
Progesterone: 259 - 979 pmol/L
Testosterone: 25 - 135 pmol/L

Below are hormonal tests that should be run to help with a variety of hormonal diagnosis. This is just a fraction of what my endocrinologist tested me for, but these are the ranges from my hospital's lab, unless otherwise noted:

Cortisol:
AM (7-9pm) serum 4.30 - 22.40 ug/ml
PM (3-5pm) serum 3.09 - 16.66 ug/ml

17-Hydroxycorticosteroid Progesterone (17-OHPS): serum
Male 0.4 - 3.3 ng/ml
Follicular Phase 0.1 - 1.2 ng/ml
Luteal Phase 0.4 - 4.8 ng/ml
(Brook Army Medical Center)

17- Alpha Hydroxycorticosteroid Progesterone (17A-OHPS): serum
Male 0.4 - 3.3 ng/ml
Follicular Phase 0.1 - 1.2 ng/ml
Luteal Phase 0.4 - 4.8 ng/ml
Oral Contraceptives up to 1.2 ng/ml
Postmenopausal up to 0.6 ng/ml
Children (1 - 15 years) up to 3.0 ng/ml
(Brook Army Medical Center)

11-Deoxycortisol (11-DOC)
Males and Females 20 - 130 ng/dl
Post Metyrapone >5000 ng/dl (5 ug/dl)
Post ACTH (60 min. after stimulation)
Males & Premenopausal Females (Follicular) 82 - 290 ng/dl
(Quest Laboratories)

Adrenocorticotrophic Hormone (ACTH):
Plasma 10 - 52 pg/ml

Glucose: Serum 70 - 105 mg/dl

Prolactin (Serum):
Males 2.1 - 17.7 ng/ml
Nonpregnant 2.8 - 29.2 ng/ml
Pregnant 9.7 - 208.5 ng/ml
Postmenopausal 1.8 - 20.3 ng/ml

Follicle Stimulating Hormone (FSH):
Males (13 -70 years) 1.4 - 18.1 mIU/ml
Normally Menstruating
Follicular Phase 2.5 - 10.2 mIU/ml
Midcycle Peak 3.4 - 33.4 mIU/ml
Luteal Phase 1.5 - 9.1 mIU/ml
Pregnant <0.3 mIU/ml
Postmenopausal 23 - 116.3 mIU/ml

Luteinizing Hormone (LH):
Males
20 -70 years 1.5 - 9.3 mIU/ml
>70 years 3.1 - 34.6
Normally Menstruating
Follicular Phase 1.9 - 12.5 mIU/ml
Midcycle Peak 8.7 - 76.3 mIU/ml
Oral Contraceptives[/u] 0.7 - 5.6 mIU/ml
Pregnant <0.1 - 1.5 mIU/ml
Postmenopausal 15.9 - 54 mIU/ml

Estrodial:
Males ND - 52 pg/ml
Postmenopausal (untreated) ND - 37 pg/ml
Menstruating
Follicular Phase
(-12) 11 - 69 pg/ml
(-4) 63 - 165 pg/ml
Midcylce (-1) 146 - 526 pg/ml
Luteal Phase
(+2) 33 - 150 pg/ml
(+6) 68 - 196 pg/ml
(+12) 36 - 133 pg/ml

ND = No detection


Thyroid Stimulating Hormone
(TSH) Sensitive
: Serum 0.35 - 5.5 uIU/ml

T4 FREE: serum 0.89 - 1.76 ng/dl

T3 FREE: serum 230 - 420 pg/dl
(Smithkline Laboratories)

Thyroxine Total: serum 4.5 - 12.5 mcg/dl
(Quest Laboratories)

Inhibin: serum
Males < 21 pg/ml
Postmenopausal < 98 pg/ml
Premenopausal < 10 pg/ml
(Quest Laboratories)

DHEA Sulfate: serum
Adult Male 80 - 560 ug/dl
Adult Female 35 - 430 ug/dl
Postmenopausal 10 - 190 ug/dl

BETA HCG (Human Chorionic Gonadotropin): serum pregnancy test
Positive >25 mIU/ml
Indeterminate 5 - 25 mIU/ml
Negative <5 mIU/ml

Well, I hope that gives you a better idea. I've gotta get some for now.

Take care

[This message has been edited by SweetJade1 (edited 08-12-2003).]

 
Old 08-30-2003, 08:21 PM   #10
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Just wanted to mention that for those of you that get an initial breakout on accutane, it MAY be because it causes Insulin Resistance in your system. Yet because it's designed to halt extra testosterone and DHT production, eventually the problem it causes (increasing those hormones) will be prevented by it. Does that make any sense?

For those that are futher interested, yes there is a gene/enzyme (possibly CYP26B1) that converts Vitamin A into 13-cis retinoic acid, but it can be defective. There's also a gene that doesn't recognize 13 cis retinoic acid (possibly CYP26A1) and that obviously will cause us various problems as well. So I suppose that's something that most or all acne sufferers lack is proper functioning of one or both of these enzymes.

Also, please remember that accutane is a TEMPORARY solution. While it has the ability to shrink sebum glands for several months or years, if Insulin Resistance is your problem, that may be why I've read on these boards people taking up to 5 courses or staying on a maintence dose. If you are one of these people, if may be in your best interest to try another way to control your hormones that does that SAME job that accutane does.

Take care =)

 
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