Gary Jackson’s “Psoriasis as a disease of Syndrome X or The Metabolic Syndrome” web page

A review of Gary Jackson’s Syndrome X Theory about psoriasis.

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For over four years, Gary Jackson (aka Evetsm or Steve M) has become more and more convinced of a strong link between psoriasis and “Syndrome X.” Late in the Summer of 2000, he created a web site describing the evidence he’s gathered,and the conclusions he’s made.[1] This article is a point-by-point rebuttal of the arguments Jackson makes.

From the very first sentence on Jackson’s web page, it is obvious that there are definition and evidence problems. Jackson claims that psoriasis is a “skin plaque disease,” which does little but trivialize it. Psoriasis is most likely a complex disease of the immune system, with a probable genetic basis.[2] There are five main types of psoriasis, but Jackson fails to make any distinctions.[3]

(Jackson also neglects to offer any evidence whatsoever to support his assertion that psoriasis “tends to first appear after the late teens in most people.” Although it is a true statement, it also trivializes the interesting age-of-onset curve of the disease, with its two distinct peaks, and the differing genetic profiles between “early onset” and “late onset” psoriasis.[4] Actually, why Jackson mentions age-of-onset at all is puzzling.)

The definition situation becomes even more challenging when Jackson says, “Psoriasis is probably a disease of Syndrome X,” and promises to show this in four ways. The first method, “using an accepted definition of Syndrome X and showing that psoriasis fits this defintion,” is fatally flawed because Jackson uses a defintion of Syndrome X accepted by nobody but Jackson himself. Why? Because Jackson fails to use a complete definition of Syndrome X. The only definition he provides us with is that it “…includes the simultaneous presence of hypertension, dyslipidemia, abnormal glucose metabolism and insulin resistance and hyperinsulinemia…” Dr. Gerald Reaven, the man who fathered research into this “metabolic syndrome,” wouldn’t stop there, however. According to Reaven, “Syndrome X is a cluster of metabolic risk factors for heart disease, separate from high total cholesterol.”[5]

Nowhere does Jackson give us a hint as to what other conditions might be considered “diseases of Syndrome X.” And in no place does he ever hint at what is cause and what is effect. Reaven often cites the “diseases of Western civilization” (high blood pressure and cardiovascular disease) as the “effects” of Syndrome X. Polycystic ovarian syndrome may also now be considered an “effect.” And all of these metabolic disturbances can be traced back to insulin resistance (IR) and compensatory hyperinsulinemia (CHI).

Jackson claims that just the concommitant risk factors are “sufficient” to show that psoriasis is a “disease ofSyndrome X,” but I doubt very much that Reaven would feel the same way. Reaven himself has shown, for example, that smoking can induce IR, and therefore Syndrome X metabolic disturbances. Smoking, according to Jackson, would then have to be considered a “disease of Syndrome X” since smoking is correlated with many of the Syndrome X risk factors. The absurd implication behind the language Jackson uses is that by treating the insulin resistance, a person should stop smoking! If Jackson were more clear about his own definitions of Syndrome X and its diseases, this rebuttal might not have been necessary.

Jackson’s definition also suffers from the fact that he fails to cite Reaven at all. Reaven is widely published and is often refered to as the expert on Syndrome X, its causes and its consequents. Jackson chooses to cite a French review of the literature[6] and a study from a single Micronesian island[7] to support his definition. The abstract of the French review gives a decent, but short definition largely matching Reaven’s.

Jackson’s grammatically-bizarre assertion that only three out of the five main markers need to be present to show that a person has Syndrome X is completely unsupported by the abstracts he’s provided, and appears to contradict Reaven’s work.

Of course, Jackson’s evidence follows his definition. He shows that a few of the metabolic disturbances associated with Syndrome X exist more often in psoriatics than in the general population. However, the way he’s written it, “In psoriasis there has been shown to be an endogenous hyperinsulinism, with insulin resistance and hypertriglyceridemia with dislipidemia in statistically significantly elevated values above normal,” would make one think that this is true for all people with psoriasis. It isn’t, and some of his own citations bear this out.

What does Jackson show us, specifically, as evidence? Given his style, it isn’t possible to say very quickly. He presents his conclusions, then follows with a list of links to Medline abstracts. He expects that, given these abstracts (and through personal communications with him, it’s obvious that he’s only ever read the abstracts of these articles, never the full text) we’ll draw the same conclusions that he has. Here, I look at each abstract, and describe what it says to me. I will do so chronologically, since it’s important in this discussion to remember that Reaven’s “breakthrough” in Syndrome X research happened in 1988.

1976 — Pfahl, et al[8] show that “major endogenous hypertriglyceridaemia” is found in 39% of psoriasis patients (although how many patients were studied is unknown — due to rounding, 39% could mean a sample size as small as 18 patients). “This study would tend to integrate psoriasis into the category of the metabolic diseases, coinciding with the notion of troubles with glucose metabolism in psoriatics,” the abstract says, “since it is now accepted that [80%] of [people with this abnormality] are pre-diabetic.” What did “pre-diabetic” mean in 1976? The abstract doesn’t say. If it means, 12 years later, that they’ve got Syndrome X, then, well, 80% of 39% is 31.2%, or well within the “1 out of 3 or 4” people in the general population with Syndrome X as stated by Reaven. We also don’t know anything about the study participants. For example, were they all French? Jackson, as we will see, has a penchant for generalizing from tiny and/or specializied samples to the global psoriatic population.

1976 — Meynadier and Guilhou[9] publish a review of all sorts of interesting metabolic changes in psoriasis. The abstract contains not a single number or percentage. I’m fairly certain Jackson includes this review solely for its mention of Syndrome X markers, but there’s so much more in it that’s also interesting and has little to do, directly, with Syndrome X. Systems other than insulin/glucose are hypothesized as perhaps being responsible for all the changes noted.

1977 — Pelfini, Jucci, Fratino et al[10] publish “preliminary results” which “seem to indicate” that psoriatics are insulin-resistant. The abstract doesn’t mention sample size, or degree of resistance at all.

1979 — Pelfini, Jucci, and Fratino, again, with a few new authors[11], publish the results of a study they did to figure out which kind of insulinogenic index best suits their desire to demonstrate the relationship between hyperinsulinemia and the diseases they have studied. This particular citation, on Jackson’s part, is worthless, as the abstract itself shows nothing in the way of new or different evidence from the study above.

1980 — Wach et al[12] publish a paper describing normal glucose levels with hyperinsulinemia in psoriatics after glucose loading — a classic sign of insulin resistance — but conclude that a connection between psoriasis and diabetes “must be denied.” Given the date, it is quite possible that the authors simply did not know that chronic IR can lead to type-II diabetes. There is no information in this abstract about sample sizes.

1987 — Valquist et al[13] show that in 20 middle-aged men, possible markers for occlusive vascular disease exist, and that the levels are correlated with psoriasis severity. To me, the wording suggests that the authors believe that the psoriasis drives the levels of triglycerides. Jackson would likely suggest the opposite is true.

1988 — Neugebauer and Weber[14] publish a study on yohimbine treatment, which reduces the secretion of insulin, in 59 psoriatics. The abstract appears to say that perhaps 88% of psoriatics are hyperinsulinemic, but without reading the full paper, it isn’t possible to say for sure. What really strikes me about this study, though,is that it appears that no thought is given to the effects of lowering insulin levels. If psoriatics have high levels due to IR, then reducing insulin secretion should make the patients hyperglycemic, and long-term treatment with yohimbine would then lead to serious type-II diabetes. Dangerous stuff, given what we know now.

1989 — Rakhmatov[15] says that 49 of 64 psoriatics (77%) are hyperinsulinemic, and states that the level of hyperinsulinism depends on the severity of psoriasis. Again, as with the Valquist study above, the abstract implies that the metabolic disturbances are caused by psoriasis, rather than the other way around.

1989 — Abramovich[16] publishes something titled “The clinical significance of dislipidemia in psoriasis patients.” Medline has no abstract for this, but Jackson cites it anyway, even though it is highly unlikely that he has read the full article. For all we know, Abramovich might say that there is no clinical significance. This citation, therefore, is absolutely worthless as support for Jackson’s point.

1994 — Offidani et al[17] publish an article describing increased lipid peroxidation — in vitro, in the presence of copper sulphate — of lipoproteins from psoriatics, and how this might suggest an increased risk for atherosclerosis. How this study methodology supports the Syndrome X hypothesis at all, I have no idea (since increased lipid peroxidation in the presence of copper sulphate isn’t something I’ve seen Reaven describe as a common condition in Syndrome X) and Jackson doesn’t say, either. In short, this is another worthless study.

1995 — Brenelli et al[18] publish a study showing no differences in glucose levels after tolerance testing, but higher insulin levels. Again, this is to be expected in IR. However, the authors tested more than just IR, and suggest that “the insulin resistance observed in psoriasis is not only related to glucose metabolism, but also to another important action of insulin, namely extrarenal potassium homeostasis.”

So, from Jackson’s own evidence (and considering the limitations of Medline abstracts), what can we safely conclude? One, that IR appears to be present in more psoriatics than in the general population. Two, that low- and very-low-density lipoprotein profiles in psoriatics may match that expected in Syndrome X. And three, that high triglyceride levels might also be present. Given the lack of concrete numbers in many of Jackson’s citations, along with the fact that not one of the studies appear to have been double-blinded, or even had a large (100 plus) sample size, jumping to further conclusions would be inadvisable.

What can we not conclude? That psoriasis is caused by IR or any other Syndrome X metabolic disturbance. Two of his abstracts imply the opposite by saying that Syndrome X marker levels are dependent upon psoriasis severity, and not theother way around.

Jackson’s second “test” of his hypothesis deals with the expression of the gene for the creation of peroxisome proliferator-activated receptors (PPARs) amongst various cell types, and drugs which activate one particular kind of PPAR (PPAR-gamma), the thiazolidinediones (TZDs). Jackson believes that since TZDs have an insulin-sensitizing effect, and are clinically effective in both IR and psoriasis, that psoriasis must be due to IR. This is naïve, as I’ve pointed out to him on several occasions, since many drugs have more than one biological effect (aspirin, thalidomide, etc).

Jackson’s first piece of evidence is a 1998 study by Rivier et al[19]. The authors were interested in learning which PPARs were expressed in differentiating skin cells. To nobody’s surprise, PPAR-alpha and PPAR-gamma mRNAs aren’t expressed as much in the keratinocytes of active psoriatic lesions as they are in normal skin. This is to be expected, since psoriatic keratinocytes don’t differentiate much at all.[20] (It is important to note that Rivier et al also showed that PPAR expression can be effected by things other than TZDs.)

Coincidentally, PPAR-gamma mRNA is also down-regulated in IR states, according to Itoh et al.[21] Hydrogen peroxide and tumor necrosis factor alpha can both suppress expression of the PPAR-gamma gene. The authors show that TZDs can recover “TNF-alpha-induced down regulation of PPAR-gamma mRNA expression.” Their abstract doesn’t mention whether or not PPAR-alpha is likewise affected, but as per Rivier et al, it too is down-regulated in psoriasis.

So, why are two PPARs down-regulated in psoriatic skin? Jackson doesn’t say, but it appears he assumes that it is due to IR and nothing else. He does not explain why this IR state does not often affect 100% of the keratinocytes (full-body psoriasis is fairly rare). He is talking about systemic IR, after all, and Rivier et al don’t specify any particular body part (such as elbow skin) in their abstract.

However, one piece of evidence that Jackson has pointedly overlooked is the TNF-alpha aspect. TNF-alpha is a potent pro-inflammatory cytokine, abundant in psoriatic skin.[22] It seems obvious that TNF-alpha-induced down-regulation of PPAR genes can be explained quite easily by the inflammation which is a characteristic of psoriasis.

Jackson’s other evidence, that one particular TZD improves psoriasis, and that TZDs have a whole host of varying actions in different metabolic pathways, does very little to support his point of view, and in some instances, contradicts it.

Jackson also reinforces his limited view of TZD action by citing a book review found in the New England Journal of Medicine (he links to Amazon.com, which has the review, but it doesn’t say what he claims it says). He also needs to learn the definition of the word “postulate.” His conclusion reads:

Based on the postulation of thiazolidinediones activity as a useful tool to identify diseases of SyndromeX, psoriasis must be seen to be a disease of Syndrome X.

Since “postulate” means “to assume without proof,” Jackson’s conclusion is that we must see psoriasis as a disease of Syndrome X based on nothing more than an assumption.

Jackson’s third point is that other diseases of Syndrome X are found more often in psoriatics than in the general population. To follow his other apparent lines of argument, we should take these findings as meaning that Syndrome X causes psoriasis. However, he once again neglects cause-and-effect entirely, since obesity, according to Reaven, is not caused by insulin resistance.[23] Obesity, especially abdominal obesity, is a recognized cause of IR.

On the other hand, since obesity is more prevalent among psoriatics, can that not explain the higher incidence of IR, Syndrome X, and heart troubles in psoriatics by itself? How about when coupled an increased incidence of smoking, or alcohol consumption, which are other lifestyles which increase the odds of Syndrome X?[24] As Poikolainen et al wrote, “Smoking and negative life events were more common among psoriasis patients than among controls, perhaps as consequences of the disease.”

So, given that psoriatics tend to weigh more, smoke more, and drink more than the general population, is it any wonder that there is increased risk of IR, and thus Syndrome X?

Also, for the sake of the argument, let’s say that psoriasis is caused by IR, and the reason we see lots of obesity among psoriatics is because the IR caused by obesity in turn causes the psoriasis. Again, the question of why the psoriasis often only affects small patches of skin becomes paramount. Why would systemic IR due to obesity affect only a few square inches of skin? Are the keratinocytes so vastly different millimeters apart? On the other hand, what makes scalp skin and elbow skin so similar that psoriasis frequently appears first in those locations? Jackson may or may not have even thought of these questions.

Jackson’s fourth point is that psoriatic mothers tend to have babies with a higher birth weight than other mothers, which fits right in with the “thrifty genotype” hypothesis. Of course, since IR can be induced by environmental factors alone (Reaven only claims that 50% of the IR picture can be attributed to genetics[25]), then there’s ample reason to believe that a mother who is IR for any reason during the course of pregnancy could give birth to a heavier baby (since if the baby is not IR, then the increased insulin coming across the placenta will have a fat-storing effect on the developing child).

Jackson then, in a “footnote,” responds to Ed Anderson’s page responding to Jackson’s newsgroup posts.[26] Jackson begins badly by claiming that Anderson believes there is “no substance” to the hypothesis, which as far as I can tell, is simply untrue and nothing more than a straw-man attack. Anderson clearly feels, as I do, that there is evidence, but it’s neither very strong nor all in Jackson’s favor.

Jackson begins with the coincidence of the two diseases. While Jackson’s own evidence shows that there is a higher incidence of type-II diabetes among psoriatics, the opposite claim, that there’s a lot of psoriasis among diabetics, is not strongly in evidence — especially as the American Diabetes Association fails to mention psoriasis as a possibility among its list of dermatological diseases that can occur in uncontrolled diabetes. This says quite a lot, actually, but Jackson has ignored it.

Even more unfortunate for Jackson, he chose to cite Bernstein once again, as he’s done several times on the psoriasis newsgroup. Jackson has letters from two of Bernstein’s patients who say that Bernstein claims that 100% of the diabetics he sees have psoriasis. The letters themselves, however, paint a very different story: we hear of Bernstein claiming that “dry skin patches” or lines in the fingernails are psoriasis. Were this actually the case, I’d hazard a guess that psoriasis incidence would jump to 50% or more of the general population, considering the booming business in sales of moisturizing products. A friend of mine frequently applies moisturizer to his hands (more than twice a day) because they become dry and annoying. It would appear that Bernstein would claim that he has psoriasis.

Such a “diagnosis” is patently absurd given the tremendous volume of medical literature on psoriasis. It shows that either Bernstein has some sort of diagnostic bias towards psoriasis, or that he’s never heard of a differential diagnosis. That Jackson continues to cite Bernstein as a reliable source of psoriasis information, despite repeated entreaties to stop doing so in the face of this absurdity, demonstrates that Jackson has a dogmatic desire to show a linkage between the two diseases, rather than, as he’s stated publicly, a desire to promote the truth.

On the site Jackson mentions, diabetes-normalsugars.com, I can find no mention of psoriasis, nor any confirmation of Jackson’s claim that Bernstein “studied diabetic dermatology for 7 years.”

Second, Jackson attempts to tackle an apparent contradiction to his theory. If, as is widely known, psoriasis often clears up during pregnancy, and pregnancy can lead to IR (gestational diabetes), doesn’t that mean that IR cannot cause psoriasis, since in pregnancy-induced IR, psoriasis should get worse, not better? Jackson tries to answer this concern with some new research into corticosteroids and IR, but fails to interpret the studies he cites correctly.[27,28] He also tosses in some blatantly incorrect guesswork about possible similarities between insulin and steroid feedback loops in the endocrine system. It’s been known for quite some time that steroids can induce insulin resistance, Bjorntorp and Rosmond are doing little more than suggesting that a genetic susceptibility exists in men for the HPA axis to go haywire and produce chronically-high amounts of corticosteroids — thus inducing IR. Not, as Jackson seems to think, for there to be some sort of “cortisol resistance” akin to IR. The researchers clearly state that the faulty receptors are central to the feedback loop (whereas the fault in IR is widespread throughout the body’s muscles and fat). In other words, only the hypothalamus need be “broken” (and thus “reading” a lower level of steroids than actually exists in the blood) for overproduction of steroids to occur. Jackson says, “There is strong evidence that in Syndrome X the cortisol feedback loop is damaged,” again confusing cause and effect, since his own references on this point state that Syndrome X exists because of an abnormal cortisol feedback loop.

And while Jackson agrees with Anderson that “immune system factors are present during pregnancy,” he then disagrees that they are present at other times. This single sentence appears to show that Jackson would completely deny what is widely recognized about psoriasis: that it is, at all times, an immune-mediated disease. Inflammation is an immune response. Steroid treatment of psoriasis inhibits the inflammation, thus clearing up psoriasis, but in large doses (usually only orally-administered) can actually induce IR.

Finally, Jackson prejudiciously dismisses another potential problem for his theory with a bunch of questions for which he largely knows the answers already. In populations with high level of IR, such as Native Americans, there is also a very low rate of psoriasis. Jackson pleads ignorance on this point, as he has for over two years despite repeatedly being shown the evidence. He’s even cited some of the answers to his own questions in the past. He knows quite well that Native Americans in general have a very high incidence of IR and the disturbances of Syndrome X — and has pointed out the Pima Indians as an example, with their 50% rate of type-II diabetes.

In the past, Jackson has also dismissed this point based on the fact that concommitance of Syndrome X diseases is unpredictable, but he obviously feels it’s okay to use disease concommitance in making his main argument. All we hear from Jackson on this question is side-stepping, stonewalling, and self-contradiction — he has no answer.

In conclusion


· Jackson uses a unique definition of Syndrome X, and doesn’t bother with the real meaning of Syndrome X at all. The best spin anyone could put on this is that all he is attempting to do is show that there is a risk of cardiovascular disease with psoriasis, but he fails to ever state his ultimate intent in any way. It has been clear, through communicating with Jackson, that he believes that IR causes psoriasis, and thus fixing the IR should also fix the psoriasis — he’s shown this belief by repeatedly suggesting that an IR-reducing diet should help reduce psoriasis symptoms. He has no evidence of this whatsoever.

· Jackson’s evidence of metabolic abnormalities in psoriasis is actually fairly scant and not highly controlled. The fact that he relies on interpretations of short abstracts — guessing as to what the researchers mean — leaves much to be desired.

· Jackson’s ideas about TZDs are naive and incomplete. He neglects the fact that TZDs have more than one biological action and that IR may be caused by more than just a “thrifty genotype.”

· Both the disease concommitance data and the heavier-birth-weight data is far from compelling when psoriatics live with risk factors for IR, possibly as a consequence of having psoriasis.

· Jackson’s attempts to answer Anderson’s criticisms of the Syndrome X hypothesis are based on number games, guesswork which appears to contradict the intent of some researchers, and a deft ability to avoid answering at all. His “answers” are completely meaningless.

Overall, Jackson fails to even postulate a mechanism whereby IR might induce psoriasis. No other “diseases of SyndromeX” are mediated by the immune system. Not one. No other disease or metabolic disturbance caused by IR appears to be inflammatory in nature. Jackson fails to state what would, in light of these facts, make psoriasis so different from other inflammatory or immune-mediated diseases that it should be included among the other diseases of Syndrome X, while the rest should not.

On the other hand, Jackson fails to mention why he believes anyone should be interested in knowing that psoriasisis a disease of Syndrome X. Giving him the benefit of a doubt for a moment, if it is because he’d like to make psoriatics aware that there is a risk of heart disease, high blood pressure, polycystic ovarian syndrome, and, in extreme cases, type-II diabetes associated with psoriasis, he could do so with just a few good references to the facts that we tend to be fat smokers and drinkers who don’t exercise, and that all of these are recognized risk factors for IR and Syndrome X.

However, all the fuss in his article, along with his communications in the psoriasis newsgroup really indicate that he believes that psoriasis is caused by IR, and that an IR-reducing diet or other lifestyle modifications aimed at eliminating this silent killer will have a beneficial effect on our psoriasis symptoms (but not Jackson’s — he doesn’t have psoriasis). He provides no evidence that Reaven’s dietary suggestions, or losing weight, or quitting smoking or drinking, or getting more exercise will have any effect on psoriasis at all. If psoriasis is caused by IR, then all five should be statistically correlated with a reduction in psoriasis symptoms, and Jackson should be highlighting such evidence as conclusive.

August 23, 2001, Update


Jackson announced an update to his page (in response to this page) on the Newsgroup, in a fairly nasty message. His update is little but a list of misunderstandings, to put it mildly.

He begins with,

DaveW has made claims that there is no substance to this IR-psoriasis hypothesis.

This is simply untrue, and Jackson knows it’s not true, because I’ve told him so, many times. The evidence shows a correlation between IR and psoriasis, there’s no dispute over that. What I’ve attempted to show is that Jackson’s evidence (and his interpretation of that evidence) does not support jumping to the conclusion that psoriasis is a disease caused by IR and CHI, which is what his page, and his newsgroup posts, either imply or state outright.

His key arguments are summarized:

Jackson is quite incorrect about what he thinks my “key arguments” are, as should be obvious by what he picks to summarize.

a) “Jackson also neglects to offer any evidence whatsoever to support his assertion that psoriasis “tends to first appear after the late teens in most people”.” Davew then says in the next sentence that “Although it is a true statement”....I guess if he knows it is true I don’t need to supply the evidence.

When critiquing Jackson’s page, I was unaware that he meant it only for me to read. Since I read it with the idea in mind that he was presenting his ideas to the world, every claim should be backed up with supporting evidence for those who aren’t as knowledgable about the subject.

b) “There are five main types of psoriasis, but Jackson fails to make any distinctions”.” Not one study that speaks of psoriasis and any factors of Syndrome X makes this distinction either.

If I believed for one moment that Jackson had read the studies he cites, instead of just the abstracts (which are summaries that don’t specify all the details), then I might believe this. Jackson’s “rebuttal” of this point is simply ludicrous in light of the fact that he relies on the abstracts.

Does this invalidate all of the studies and all other studies that mention psoriasis without typing ? This would leave us with very few psoriasis studies of any sort.

Of course it doesn’t invalidate the studies. My statement that Jackson makes no distinction is simply to point out the fact that he is making broad generalizations, and since he doesn’t appear to read full articles, he’s doing so from very little data.

c) Davew says that I don’t use Reaven’s definition of syndrome X : “Syndrome X is a cluster of metabolic risk factors for heart disease”.” Well, Davew, what are “includes the simultaneous presence of hypertension, dyslipidemia, abnormal glucose metabolism and insulin resistance and hyperinsulinemia” if not risk factors for heart disease ?

When has psoriasis been considered to be a metabolic disease? Also, as I pointed out above, Jackson makes no claims about cause-and-effect. He’s never come right out and said, “psoriasis increases the risk of heart disease,” for example. Without showing how psoriasis adds to the risk of heart disease, calling it a “disease of Syndrome X” makes no sense. And if the basis for calling it such is simply disease concomitance, then why psoriasis is linked to other diseases like it is becomes of the utmost importance. Jackson has shown little interest in “why?” however.

d) “Nowhere does Jackson give us a hint as to what other conditions might be considered “diseases of Syndrome X”. I do they are listed above under “Diseases of Syndrome X with significantly above normal co-commitance in psoriatics”

And as I have already shown, obesity is not caused by Syndrome X, but is a cause of Syndrome X. According to Reaven, the claims that insulin resistance makes a person obese (or just makes it more difficult to lose weight) are “Not True!”[23] If both the causes and effects of IR and CHI are “diseases of Syndrome X,” it makes the term almost meaningless.

e) “Smoking, according to Jackson, would then have to be considered a “disease of Syndrome X”. No, smoking may contribute to the cause of diseases of Syndrome X. It is an external input that exerts influence on IR and other factors in Syndrome X.

But if it fits the “definition” that Jackson puts forth (“includes the simultaneous presence of hypertension, dyslipidemia, abnormal glucose metabolism and insulin resistance and hyperinsulinemia”), then why isn’t smoking a “disease of Syndrome X?” This is an example of why it is a poor definition.

f)“In psoriasis there has been shown to be an endogenous hyperinsulinism, with insulin resistance and hypertriglyceridemia with dislipidemia in statistically significantly elevated values above normal,” would make one think that this is true for all people with psoriasis. It isn’t, and some of his own citations bear this out.” Statistical observations NEVER include the word ALL, they contain only statistical significance. That is why they are called statistical observations.

This response misses my point. Jackson’s own citations show that some psoriatics do not show significantly elevated values of these conditions. Also, his citations point these things out independently of one another, for the most part, so his use of the words “with” and “and” are inappropriate.

g)DaveW claims that all 11 studies that I cite that make statements connecting psoriasis with insulin resistance are wrong.

This statement is a perfect example of how Jackson fails to understand what I write. I never claimed that even one of those studies was “wrong,” and I challenge Jackson to point to any sentence I’ve ever written on this subject that says that. In fact, I believe that for the most part, they are as “correct” as they could be at the times and conditions under which they were completed. What I think is “wrong” is Jackson’s interpretations of those study abstracts, and the conclusions he jumps to because of those interpretations.

First the fact that there are at least 11 studies linking psoriasis and insulin is in itself significant.

I never said it wasn’t.

Second all his critisizms are of the statistical methods employed. The correctness of statistical methods used are implied in the the concluding statements in the abstract, since in order to make those statements the statistical criteria must have been met and reviewed before publishing.

Absolutely. But meeting some sort of statistical criteria does not mean that the data itself is any good. Small studies with no blinding can show “statistically significant” results quite easily without being correct, and still be published in major medical journals. Otherwise, there would be no need for further testing. Jackson’s insistence that peer reviewers are somehow god-like in their ability to sort truth from falsehood is absurd, given the number of published studies which have turned out to be wrong upon further investigation.

Davew, , [sic] who admits to having not a single day of math statistical training. . .

When did I ever admit to any such thing? It’s not true, why would I “admit” to a lie?

. . .show us the statistical math explaining why all those studies have the wrong conclusion or are insignificant.

See above. Jackson’s challenge here is for me to prove what he and I both know to be wrong. It’s absurd.

h) “Jackson believes that since TZDs have an insulin-sensitizing effect, and are clinically effective in both IR and psoriasis, that psoriasis must be due to IR. This is naive”. This is a postulate, made in two published papers, one review pulished in the NEJM, and are entirely reasonable and they are not my own. The TDZs are proposed as tools to show that a disease is likely to be a disease of Syndrome X and is merely one data point among many in my postulate.

Again, Jackson is obviously unaware of what the word “postulate” means. That he calls his own ideas “postulates,” when he certainly is backing them up with evidence, just proves my point. From the book review Jackson cites: “The availability of thiazolidinediones that act directly to reduce insulin resistance may prove the most rapid route to defining unambiguously the role of insulin resistance in the pathophysiology of the diverse disorders to which it has been linked.” Emphasis mine, as it means that taking the use of this “tool” as a given is unreasonable.

i)“This is to be expected, since psoriatic keratinocytes don’t differentiate much at all”. What does this mean ? I’m sure that they don’t differentiate. They probably don’t even discriminate or pontificate.

This illustrates Jackson’s lack of basic medical knowledge about psoriasis[20].

j)“However, he once again neglects cause-and-effect entirely, since obesity, according to Reaven, is not caused by insulin resistance.23 Obesity, especially abdominal obesity, is a recognized cause of IR.” Davew keeps seeing IR and psoriasis, or IR and any diseases of Syndrome X, in a simplistic cause and effect unidirectional relationship. This mechanism is not linear with one factor strictly proceeding the other, rather, it is an example of the positive feedback loop in effect, where cause and effect are interchangeable and are self-reinforcing.

Interchangeable?!? Jackson fails to see here that some things are, indeed, recognized as causes of the abnormalities in the insulin/glucose feedback loop, and that those abnormalities cause other conditions, without feeding back into the root problem(s). To see the whole gamut of conditions as a whole slew of interconnected feedback loops is to make the term “Syndrome X” meaningless. Jackson also fails to provide any evidence that cause-and-effect are truly interchangeable. For example, evidence that supports the contention that insulin resistance is caused by hypertension, or dyslipidemia, or a heart attack, or any evidence that obesity is caused by insulin resistance.

However, the origins of Syndrome X are given by the thrifty genotype hypothesis

http://www.mercola.com/2000/nov/19/genotype.htm

Jackson apparently hasn’t read this in detail. Neel provides evidence that Syndrome X diseases are probably not due to the same genetic disorder. Even then, the Thrifty Genotype Hypothesis is just one of many root causes of insulin resistance, but it seems that Jackson believes it is the main cause. The Mercola article Jackson cites here shows that, perhaps, a Thrifty Gene can explain 33% of the occurances of the diseases under study. It’s quite obvious that physical activity and obesity play a large role in causing insulin resistance, with or without any Thrifty Gene.


I dealt with this study he cited in response to Ed Anderson above. Jackson appears to think that this is a “refinement” to the Thrifty Gene hypothesis, when all it really is, is another, different, feedback loop which can induce insulin resistance, with its own genetic basis.

In conclusion, until Davew understands the difference between a linear, uni-directional, cause and effect and the interchangeable cause and effects of a positively disturbed feedback control loop, he will always search in vain for IR as an absolute cause or effect of diseases of Syndrome X.

Considering that I am not searching for IR as an asolute cause or effect of anything, the above is absurd. Just another example of Jackson putting his own words in my mouth.

Understanding the Thrifty-Genotype hypothesis will help him grasp how this feedback control loop is originally disturbed and what people are likely to be susceptible.

I already know this, and more, as should be obvious from the above.

Second, until Davew stops thinking in absolutes and starts thinking statistically and probabilistically, and until he graps the implications of the phrase “statistical significance”, he will forever believe that I have to be either completely wrong or completely correct.

Again, Jackson is inventing beliefs for me, and nothing more. Right now, I believe he is only a little bit correct, but mostly wrong. For example, he’s completely wrong in thinking that I think only in absolutes.

I won’t go into the rest of his document, because based on the spuriousness of what he has already said, the rest is moot.

It’s quite obvious that “I won’t go into” means “I stopped reading.” Had Jackson kept reading, he would have, for example, picked up on the fact that I’d already shown his ideas about the “cortisol hypothesis” to be without support from the studies he cited. (Jackson has admitted that he stops reading my Newsgroup posts halfway through, and believe I can safely assume he did nothing different with regards to this page. The fact that he says in his announcement of his update that he “stumbled yesterday upon more of the accusatory dreck that you litter over the internet,” means he never once followed the link to this page that I provided for him at least twice, but instead probably found this page through some search engine.)

To conclude this update, I believe it’s fairly obvious that Jackson doesn’t know or understand what my “key arguments” are, even after years of open and honest discussion, and is therefore making “conclusions” about my position without a full comprehension of my points. This “rebuttal” of his is little but falsehoods, straw men, and more of the same willful ignorance that Jackson has used throughout the years. It does nothing to either support his own argument or discredit mine.

March 14, 2002, Update


On February 26, I wrote in the Newsgroup about how a couple of Jackson’s own citations seem to state that insulin-resistance markers are driven by the severity of psoriasis, and not the other way around. I wrote about this in the main article, above, as well. Thirteen days later, Jackson replied with another wave of his “feedback” magic wand, and seemed to think that would suffice for an explanation.

So, I made a comment that such an idea seemed to indicate a rather different attitude from previous discussions, in which Jackson had soundly ridiculed the idea that psoriasis could, in any way, cause insulin resistance. I also asked for any evidence he might have of the feedback loop he mentioned.

He chose to restate his overall hypothesis about the Thrifty Gene, Syndrome X, and psoriasis, which is completely irrelevant to the comment I’d made about his position softening, and not any sort of answer to the question of evidence I’d asked him. When I pointed these things out to him (and finally got around to putting the first update, above, here on this page), he chose to reply to a single sentence of the update:

This is an example of just how confused you are on this. Now you write on that webpage of yours :

“Without showing how psoriasis adds to the risk of heart disease,
calling it a “disease of Syndrome X” makes no sense.”

You ask the wrong questions because you obviously believe that
psoriasis initiates all this and that people with psoriasis have
Syndrome X because of the psoriasis via the induction of heart
disease. No ?

How can that be ?

As far as I know, it isn’t. The proper scientific/skeptical viewpoint of the Syndrome X link to psoriasis is that until more information and evidence is gathered, the current evidence cannot support, on its own, the conclusion that psoriasis is caused by insulin resistance, or that it is “a disease of Syndrome X.” Even Reaven seemed uninterested in the question (but perhaps only for practical reasons).

If I “obviously believe” anything, it’s that Jackson has jumped to conclusions. I certainly do not believe that psoriasis “initiates all this.” It seems, to me at least, that Jackson finds it necessary to exaggerate my beliefs (or even fabricate them) in order to attack them. This is a classic straw man — instead of responding to what I actually say, Jackson is making mincemeat of oversimplified or overblown positions which I do not hold. While this makes it much easier on him, it does absolutely nothing to refute my arguments.

Also, I haven’t been asking “wrong questions,” I’ve simply been asking questions which Jackson refuses to answer. Given his tendency to not read what I write, it seems likely that he is not even aware of most of the questions I’ve asked him over the years.

But Jackson continues, stating a couple of “FACTS” which, as I’ve already shown in the main article, above, aren’t so much “facts,” but are instead misleading, context-free abbreviations of actual facts. Jackson appears to be comfortable throwing away “the big picture” in favor of making arguments based on half-truths, but I’m not. Since I’ve already dealt with these two “facts” (see the main article, above), I won’t bother doing so again here.

Jackson then says,

These 2 facts say that psoriasis is LIKELY to be a disease of Syndrome X.

Jackson continues to imply that insulin resistance causes psoriasis, without stating it outright. If that’s not his intent, then all this talk of psoriasis being a “disease of Syndrome X” is meaningless. Why? Because if you remove both the cause (insulin resistance) and the effect (heart attacks — as he does, below), then all you’re left with is a label which carries with it no suggestions for prevention, treatment, or consequences. Since this would mean that six years of his posts to the newsgroup — presenting evidence, arguing his case, etc. — would have been worthless, medically, I cannot accept that the implication isn’t there. This is further backed up by another newsgroup post of his, which I will get to in a few paragraphs.

So, what does it mean if psoriasis is a disease caused by insulin resistance? It means that we should be able to treat the disease by controlling that resistance, possibly even through a careful diet and exercise, without drugs, messy ointments, or the like. There is no good evidence that this is the case. It would be wonderful if there were.

Jackson again:

Don’t get your pyramid head into a knot wondering if psoriasis causes heart disease. It may, it may not. It does not further the argument that psoriasis is a disease of syndrome X. It is a non sequiter. [sic] It is beside the point. It is superfluous.

The funny thing about this is that the whole heart attack angle, while definitely important, is really beside my main point. That Jackson wastes so much time on calling it a waste of time, time he could have better spent answering the other issues both in my main article and the first update, says quite a bit about him. He is once again stonewalling on the really central questions, and appears to be purposefully evading all attempts at reaching an understanding.

Its the definition, stupid !

And the fact that he is, again, stooping to base insults strongly suggests that he really has no good response to any of the important points.

Now let us not disrupt this group with this crud !

This was the last sentence of that newsgroup post. Jackson was unable to follow his own suggestion, however, and just a few hours later, before I had a chance to reply, he posted another message, which begins by listing a bunch of studies which show that a specific type of fat is a probable cause of insulin resistance. I can only guess that he’s done this because he thinks I don’t believe this is true. If so (and I don’t know of any other reason why he would do such a thing), then he is, of course, wrong, but since he doesn’t read what I write, he wouldn’t know.

Once again, Jackson shows how easy it is to get confused by all these articles. Regardless of the good evidence he’s been shown (and has shown himself) that insulin resistance can be caused by a number of things, what does he claim? He claims that “visceral adipose tissue […] is the cause of insulin resistance” (emphasis mine). This is not a conclusion supported by the evidence he provides.

For example, one of the citations he provides (Peng and Gao, 2000) states, “The abdominal subcutaneous adipose tissue of type II diabetic patients, as visceral adipose tissues, contributes to their insulin resistance” (emaphasis mine, again). Not “causes,” but “contributes to.” Another, Lebovitz, 2001, relates three distinct possible causes of insulin resistance.

This is a case where the reality of the situation (already known to Jackson) is simply ignored in favor of preaching dogma. After all, if there exist causes of insulin resistance other than visceral adipose tissue, then he could not make his latest attempt at an argument very convincing at all. After quoting nine articles, none of which state anything as strong as Jackson’s claim, he finally gets around to his point:

Isn’t it coincidental ?

Psoriatics are often overweight. Psoriasis improves with weight loss.
Insulin resistance improves with weight loss. Psoriasis lesions, as
you claim, is NOT likely the cause of IR.

I don’t believe I’ve ever once claimed that psoriasis lesions were a “likely” cause of insulin resistance. I presented the idea as a possibility. There is evidence that the inflammation of psoriasis can contribute to insulin resistance (through tumor necrosis factor alpha), but that’s irrelevant to this point: Jackson is once again inventing claims for me. Claims with which I do not agree. This is just more evidence that Jackson does not understand my objections. Or, if he does understand, then he’s doing nothing but constructing more straw men to attack.

I’ll spell it out, once again, in terms related to the above argument: nothing that Jackson has shown or argued to date makes it likely that insulin resistance is the cause of psoriasis. The very fact that psoriatics tend to be obese is, to me, the likely cause of the increased prevalence of insulin resistance among us. The fact that we tend to smoke and drink more than the general population also contribute to the findings of insulin resistance. Apply Occam’s Razor, and the idea that insulin resistance causes psoriasis is sliced into tiny pieces.

Of course, in the above argument, he’s inventing much more than just claims for me. The claim,

Psoriasis improves with weight loss.

is completely unsubstantiated. There has been no good evidence of this presented in the medical literature, and no scientific evidence whatsoever (of any quality), since, at the latest, 1969. At least, I have yet to find any, and I’ve been looking for more than two years. One would think that if the claim were true, it’d be widely publicized. It isn’t. I don’t know where (or even if) Jackson has found evidence for this statement, but it’s not the first time he’s made it. Repeated requests for citations supporting the idea that psoriasis improves with weight loss were met with no response. Once again, we can see that Jackson is uninterested in trying to find out what the truth of the psoriasis/IR relationship is, but instead uses a fabrication to support what appears to be a flimsy position.

Jackson ends this particular assault on logic with:

Maybe you will take that rubbish off the internet now ?

I’ll leave it to the reader to decide who is publishing rubbish. And, even if Jackson is correct, since his own writings on the Internet lack rigor and support, I’ll be leaving this page up for at least as long as he leaves his up, or changes it to provide better information.

Then, the next day, again ignoring his own suggestion that we avoid “disrupting this group,” Jackson posted another abstract which shows, yet again (this is getting tiresome), that psoriasis is correlated with the metabolic disturbances of Syndrome X (Rocha-Pereira et al, 2001). While we know this already, this study is perhaps the best of the bunch that Jackson has presented.

But, again (and I know this also is getting tiring), Jackson’s reason for posting this abstract, and making a big “stink” over it, is most likely because he refuses to believe that I believe that psoriasis is, indeed, correlated with Syndrome X abnormalities. My only point since putting up this page has been that none of the evidence presented so far, not even this latest study, shows any sort of cause-and-effect relationship, but it’s clear that Jackson thinks that insulin resistance causes psoriasis. Otherwise, why spend so much time and effort?

Concluding this update, it’s clear that Jackson is answering questions I no longer ask, and haven’t asked in quite a long time. I guess now I’ll wait to see which single sentence he chooses to reply to next. I hope he’ll surprise me, by presenting something new, relevant, and perhaps even compelling, but I won’t be holding my breath.

March 17, 2002, Update


I was wrong. Jackson didn’t reply to a single sentence of my latest update, he didn’t bother to reply to the update at all. Instead, Jackson is further disrupting the Newsgroup (as he said we shouldn’t) with posts about how visceral fat causes insulin resistance and how visceral fat is a source of tumor necrosis factor alpha (TNFa).

We know these things already. This is old, boring stuff.

That Jackson chooses to bring up a post of mine from September of 2000 shows that he’s completely confused about who’s arguing what today. It appears, however, by his insistence on this connection to adipose tissue, that he still believes that “visceral triglycerides” are “uniquely necessary for the existance of TNF.” If Jackson wants to roll the clock backwards 19 months, I’m game (especially since he is so very incorrect on that point).

TNFa is a potent pro-inflammatory cytokine, which means it may be partially responsible (along with other pro-inflammatory cytokines) for the inflammation which is a characteristic of psoriasis. It is not produced only by adipose tissue, but from a large number of sources. From Jackson’s own citations, for example, we can learn:

TNF is produced primarily by macrophages, however it has also been demonstrated to be synthesized and secreted by adipose tissue.

Philip H. PekalaBroken Link

Are macrophages (white blood cells which engulf and destroy invading organisms) involved in psoriasis? Absolutely:

T-lymphocytes and macrophages were the predominant inflammatory cells [found in psoriasis lesions].

Bjerke et al, 1978

We also know that the T-lymphocytes are capable of producing TNFa, from Austin, et al (1999). And Lange, et al (1998) showed that even keratinocytes (skin cells) are capable of producing TNFa (presumably in order to begin an inflammatory immune response to a threat, or perceived threat). In light of this evidence, Jackon’s old position on the source of TNFa is simply ludicrous.

Jackson’s citations also tell us:

Thus, adipose TNF-alpha and ASP seem to be important autocrine factors that inhibit and stimulate triglyceride storage in the adipocyte, respectively.

Vanessa van Harmelen

and:

In fact, only 5-6% of insulin sensitivity variation is explained by circulating levels of TNF-alpha. Rather, the action of TNF is local (i.e., autocrine or paracrine), shown through studies of explanted SAT, in which the higher the level of TNF-alpha, the more inhibition of insulin-stimulated glucose transport into the adipocytes was seen.

Peter AmerBroken Link

The above two quotes confirm what I learned when I first began researching TNFa in relation to psoriasis. Insulin forces adipocytes (fat cells) to take in glucose, and store it as triglycerides. When the fat cells get too fat, they begin producing TNFa in order to force themselves to become insulin resistant, and thus stop or slow intake and storage of glucose. After all, the “auto” part of “autocrine” in the above quotes means “self.” This is a nifty feedback loop, but has very few implications for the disease progress seen in psoriasis, since TNFa is produced on its own, locally to psoriasis plaques. It also does little to foster overall insulin resistance, which is mostly a function of skeletal muscle.

Psoriasis lesions probably produce much less TNFa than fat cells. But, any TNFa produced by the immunological processes in a psoriasis lesion which happen to get to the general blood flow can, indeed, contribute to insulin resistance in adipose tissue. How much this contributes is not known. Several studies have found no correlation between blood levels of TNFa and severity of psoriasis, but these appear to be contradicted by later studies. Also, Ljungqvist, et al (1998?)Broken Link claim that any major injury, including surgery, induces insulin resistance. Injury invariably involves inflammation, as does psoriasis.

Until further research is done, the TNFa aspect of psoriasis is a dead end as far as insulin resistance is concerned. There’s not enough evidence to show that TNFa produced in psoriasis plaques causes significant insulin resistance (although theoretically it can exacerbate insulin resistance, and thus Syndrome X). And while blood-borne TNFa produced by adipose tissue can conceivably exacerbate psoriasis, there doesn’t appear to be any evidence whatsoever that it is involved in the pathogenesis of the disease.

To conclude this update, the idea that TNFa is only produced by visceral adipose tissue is the only position Jackson can take which would help him show that psoriasis is caused by insulin resistance, much like his false statement that psoriasis is relieved through weight loss (see the March 14, 2002, update, above). Contradictory evidence from his own citations was ignored in favor of this fabrication. It would seem, therefore, that Jackson is a victim of Morton’s Demon:

Morton’s demon was a demon who sat at the gate of my sensory input apparatus and if and when he saw supportive evidence coming in, he opened the gate. But if he saw contradictory data coming in, he closed the gate. In this way, the demon allowed me to believe that I was right and to avoid any nasty contradictory data.

…Morton’s demon makes it possible for a person to have his own set of private facts which others are not privy to, allowing the [victim] to construct a theory which is perfectly supported by the facts which the demon lets through the gate. And since these are the only facts known to the victim, he feels in his heart that he has explained everything. Indeed, the demon makes people feel morally superior and more knowledgeable than others.

The demon makes its victim feel very comfortable as there is no contradictory data in view. The demon is better than a set of rose colored glasses…


Talk.Origins Archive Post of the Month for February 2002

Jackson’s insistence that I keep this page on the web “for posterity” is a clear indication he thinks I am just plain wrong about everything I write. That he refuses to read and understand what I write shows that Morton’s Demon is working up a sweat in his head. In short, at this point in time (while the demon is functioning), Jackson appears to be beyond reason. An open, honest discussion with him is an exercise in futility, regardless of his previously-stated desire for such a debate.

March 18, 2002, Update


Morton’s Demon has been hard at work again. Jackson writes:

Davew, you are right, not only is their [sic] little evidence that psoriasis produces TNF that causes IR, there is NO evidence.

That’s part of the reason why this avenue of thought is, currently, a dead end. Jackson doesn’t appear to agree that the other part of the TNF scenario is also a dead end.

There is some evidence that TNF is marshalled from adipocytes to produce inflammation in wounds…

There is? Where? What evidence is there that the TNFa which induces inflammation in wounds comes from adipocytes? This would mean that injury-induced insulin resistance follows a convoluted pathway: wound occurs, something signals from the wound to the adipocytes that the wound occured, the adipocytes respond by dumping out lots of TNFa, which would somehow preferrentially induce inflammation at the wound site. Jackson has yet to show what the “something” and the “somehow” are.

What’s more likely (without resorting to “somethings” or “somehows”) is that a wound induces the local skin cells and local immune cells to produce lots of inflammation, in order to defend the body from invasion by pathogens from outside. The massive amounts of TNFa released in this process could coincidentally cause insulin resistance, since TNFa has more than one function in the body. And to drive this point home, relative to the skin, Michael I. Luster wrote an editorial titled “Inflammation, Tumor Necrosis Factor, and Toxicology” (1998) which says, in part,

In the skin, TNFa gene expression occurs in the epidermis within minutes after either physical disruption (UV irradiation, burns, wounding) or application of chemical sensitizers or irritants. The function of TNFa in allergic and irritant contact dermatitis is similar to its role in other organ systems and involves regulation of immune and inflammatory processes. An additional role for TNFa in the skin is to provide a signal for Langerhan’s cell migration from the epidermis to the draining lymph node, an event required for induction of an immune response. Similar to other organ systems, diminished responses to contact allergens and irritants are observed in the skin of mice rendered deficient in TNFa responses either through genetic alterations or administration of neutralizing agents.

It’s important to note that Luster is talking about cells in the skin expressing the gene for the manufacture of TNFa, and not about the general levels of TNFa itself (which Jackson could otherwise claim comes from fat). The only conclusion a reasonable person can draw is that TNFa is created in the skin itself, at the start of an immune and inflammtory response. And, in contrast to Jackson’s postulates, Luster fails to mention adipocytes or adipose tissue (visceral or otherwise) at all in an otherwise highly informative editorial.

Jackson’s sentence continues:

…and that there is transitory IR…

Yes…

…but there is however volumes of concrete, iron cast evidence, that adipose fat causes IR…

Well, 5 to 6% of the variation in insulin resistance can be explained by serum TNFa levels. Since visceral adipose tissue appears to be the primary source of free-floating, serum TNFa, then one might conclude that only 5-6% of the variation in IR can be explained by variations in total visceral adipose tissue.

…and inflammation…

Systemic inflammation, yes, as shown by Jonkers, et al (2002). But what about the massive, localized inflammation of psoriasis? After all, people who are insulin resistant aren’t walking around as red as lobsters from the inflammation, are they? Is a chronic blush often found in type-II diabetics? Where is the mechanism through which visceral adipocytes trigger the tremendous immune response seen in psoriatic skin, local to the plaques, and absent from skin just millimeters away?

…and reducing fat reduces IR…

Definitely.

…inflammation…

Again, systemic inflammation. I haven’t seen any evidence that localized inflammation, from wounds or other immune-system processes, is any less severe in lean people than in fat people. Jackson will need to provide such evidence in order to make this point valid in relation to psoriasis.

…AND reduces psoriasis !

Again, there is no “concrete, iron cast evidence” that this is true. See above, in the March 14, 2002 update. Jackson must either show this to be the case, or stop using this made-up “fact” in his arguments.

AND using drugs that specifically act on adipose to reduce IR clears psoriasis.

The TZDs again. The fact that TZDs have many different effects on human biology is ignored by Jackson, as shown above, in the main article. See also Pershadsingh, et al (1998) for a host of possible mechanisms through which TZDs can have direct effects on the disease process of psoriasis, independent of their effects on insulin resistance.

You see the pathway of action ? They do not act directly on the inflammation (psoriasis etc) they act on the fat to clear the psoriasis. ie the source of the mediators of inflammation is in the fat.

I see a convoluted and bizarre pathway of action. A much more direct pathway of action for TZDs in psoriasis is that they up-regulate the gene for PPAR-gamma receptors of keratinocytes in the skin (which is down-regulated by TNFa generated by macrophages, T-cells, and keratinocytes in the skin), thus allowing the skin cells to differentiate properly. This action of improving keratinocyte differentiation is also key to the action of Dovonex, so this method of treatment is not without precedent.

If psoriasis inflammation produced IR then clearing IR cannot clear psoriasis !

The implication here is clear: Jackson believes that clearing insulin resistance does clear psoriasis. Since that is, in effect, what Jackson is trying to prove, his argument has become circular. Using the conclusion one wishes to reach as an assumption in the argument you present (in order to reach that conclusion) is simply bad logic.

You cannot clear a cause by clearing the effect.

This is simply irrelevant, since the premise is logically flawed.

Here’s why :

Jackson goes on to quote two papers, neither of which mention psoriasis, but instead talk about one of the many effects of TZDs. He is simply blinding himself to simpler explanations which cover much more of the available data, than just the tiny, select sub-set of facts and fabrications he’s looking at.

So far, Jackson has committed several of the “fallacies in logic and rhetoric” which Carl Sagan pointed out the chapter “The Fine Art of Baloney Detection” in his book, The Demon-Haunted World: Science as a Candle in the Dark:

Ad Hominem: calling me “stupid,” a “taskmaster,” etc.

Argument from Authority: citing Bernstein as the only evidence that “all diabetics have psoriasis”

Begging the Question: assuming that psoriasis clears if insulin resistance is lowered

Observational Selection: believing that TNFa comes from only one source, or that TZDs act in only one way

Statistics of Small Numbers: the use of studies with low numbers of participants as evidence

Excluded Middle: since I disagree with Jackson, he appears to think that I must always believe that psoriasis causes insulin resistance

Confusion of Correlation and Causation: the idea that since psoriasis is correlated with insulin resistance, it must be caused by insulin resistance (Jackson’s premise, as far as I can tell — see also “begging the question,” above)

Jackson also fails to employ several of the “tools” which Sagan advises we all learn:

Independent confirmation of the facts: Jackson has yet to provide good evidence that psoriasis improves with weight loss (see “Begging the Question,” above)

Encourage substantive debate on the evidence: attempts at good debate are often met with one or more of the fallacies listed above — especially Ad Hominem — which discourage debate through their irrationality

Spin more than one hypothesis: it’s obvious Jackson has only one hypothesis

Try not to get overly attached to one hypothesis just because it’s yours: Jackson’s ad hominems (see above) in response to criticisms of his hypothesis suggest that he takes this very personally

If there’s a chain of argument, every link in the chain must work: the logical chain Jackson tries to follow is broken in several places — and in the past, he’s asked us to ignore breaks in that chain in favor of the “overall” evidence

Occam’s Razor: Jackson’s ideas fail to explain the data equally well as other hypotheses, so the Razor doesn’t even need to come into play, except for particular details

Can the hypothesis be falsified?: given that Jackson begs the question (see above), then no, it cannot be falisfied

Nothing Jackson has shown indicates anything other than that Syndrome X and psoriasis are independent conditions which can complicate each other through interactions of TNFa (and perhaps other cytokines). A similarity in risk factors easily explains their comorbidity.

Jackson postulates no mechanism through which insulin resistance might cause psoriasis (which involes many biological changes other than inflammation). His hypothesis makes no testable predictions which aren’t already assumed to be true by him (the hypothesis cannot, with Jackson’s apparent point of view, be falsified). This is amatuer-level pseudo-science — easily-detectable “baloney” — illustrated also by the fact that of all the studies (well, abstracts) showing a correlation between Syndrome X metabolic changes and psoriasis, not a single professional researcher (who’s medical knowledge is far beyond either Jackson’s or my own) even hints that psoriasis might be caused by insulin resistance.

Footnotes


1. Psoriasis as a disease of Syndrome X or The Metabolic SyndromeBroken Link, Jackson G, 2000

2. What is Psoriasis? from the National Psoriasis Foundation

3. Types & Severity of psoriasis from the National Psoriasis Foundation

4.Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris.” Henseler and Christophers, J Am Acad Dermatol 1985 Sep;13(3):450-6

5. What is Syndrome X?Broken Link from the Syndrome X Universe

6. “[The importance of syndrome X in daily practice.]” Daubresse, Rev Med Brux 2000 Dec;21(6):473-7

7.Epidemiology and factor analysis of obesity, type II diabetes, hypertension, and dyslipidemia (syndrome X) on the Island of Kosrae, Federated States of Micronesia.” Shmulewitz et al, Hum Hered 2001;51(1-2):8-19

8. “[Hyperlipoproteinemias in psoriasis.]” Pfahl et al, Ann Dermatol Syphiligr (Paris) 1976;103(1):15-22

9. “[The biochemistry of psoriasis.]” Meynadier and Guilhou, Ann Dermatol Syphiligr (Paris) 1976;103(5-6):525-45

10.Psoriasis and insulin secretion. Preliminary results.” Jucci et al, Arch Dermatol Res 1977 Jan 31;257(3):239-46

11.Insulinogenic indexes in psoriasis.” Pelfini et al, Acta Derm Venereol Suppl (Stockh) 1979;87:48-50

12. “[Glucose assimilation, insulin secretion and insulin sensititivy in psoriasis patients.]” Wach et al, Z Hautkr 1980 Apr 1;55(7):421-32

13.Serum lipoproteins in middle-aged men with psoriasis.” Vahlquist et al, Acta Derm Venereol 1987;67(1):12-5

14. “[Somatostatin deficiency, hyperinsulinism and thrombocyte aggregation in psoriasis.]” Neugebauer and Weber, Z Hautkr 1988 Jul 15;63(7):585-6, 589-90

15. “[Characteristics of basal insulinemia in patients with psoriasis.]” Rakhmatov, Vestn Dermatol Venerol 1989;(10):44-7

16.The clinical significance of dislipidemia in psoriasis patients.” Abramovich, Acta Derm Venereol Suppl (Stockh) 1989;146:216

17.Lipoprotein peroxidation in adult psoriatic patients.” Offidani et al, Acta Derm Venereol Suppl (Stockh) 1994;186:38-40

18.Insulin resistance in psoriasis.” Brenelli et al, Braz J Med Biol Res 1995 Mar;28(3):297-301

19.Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes.” Rivier et al, J Invest Dermatol 1998 Dec;111(6):1116-21

20. “[Psoriasis. Pathogenesis.]” Ortonne and Ortonne, Presse Med 1999 Jun 26;28(23):1259-65

21.Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma.” Itoh et al, Clin Exp Pharmacol Physiol 1999 Jul;26(7):558-60

22.The Cytokine Network in Lesional and Lesion-Free Psoriatic Skin is Characterized by a T-Helper Type 1 Cell-Mediated Response.” Uyemura et al, Journal of Investigative Dermatology 1993 Nov;101(5):701-5

23. A comment from ReavenBroken Link from the Syndrome X Universe

24.Smoking, alcohol and life events related to psoriasis among women.” Poikolainen et al, Br J Dermatol 1994 Apr;130(4):473-7

25.Syndrome X: Ten Years After”, Reaven G, Drugs 1999; 58 Suppl. 1: 19-20

26. Psoriasis as a risk factor for type II diabetes Anderson E, 2000

27.Hypothalamic origin of the metabolic syndrome X.” Björntorp and Rosmond, Ann N Y Acad Sci 1999 Nov 18;892:297-307

28.Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus.” Björntorp et al, Diabet Med 1999 May;16(5):373-83