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Sugar, testosterone and oestrogen

Posted: Mon Nov 12, 2007 5:53 am
by TwistedHelix
I thought this new discovery might have some relevance to MS: we know that the level and ratio of oestrogen to testosterone is important in neuroprotection, and finding that a diet high in sugar can destroy that balance fits in very nicely with the fact that MS seems to go hand in hand with a modernised, (and therefore high sugar), lifestyle. The only spanner in the works is that this article suggests high levels of hormones whereas men with MS tend to have a lower level of testosterone, but anything outside the normal range can be harmful to the central nervous system,

Too much sugar turns off gene that controls the effects of sex steroids
New research supports advice to eat complex carbs and avoid sugar

(Vancouver – November 8, 2007) – Eating too much fructose and glucose can turn off the gene that regulates the levels of active testosterone and estrogen in the body, shows a new study in mice and human cell cultures that’s published this month in the Journal of Clinical Investigation. This discovery reinforces public health advice to eat complex carbohydrates and avoid sugar. Table sugar is made of glucose and fructose, while fructose is also commonly used in sweetened beverages, syrups, and low-fat food products. Estimates suggest North Americans consume 33 kg of refined sugar and an additional 20 kg of high fructose corn syrup per person per year.

Glucose and fructose are metabolized in the liver. When there’s too much sugar in the diet, the liver converts it to lipid. Using a mouse model and human liver cell cultures, the scientists discovered that the increased production of lipid shut down a gene called SHBG (sex hormone binding globulin), reducing the amount of SHBG protein in the blood. SHBG protein plays a key role in controlling the amount of testosterone and estrogen that’s available throughout the body. If there’s less SHBG protein, then more testosterone and estrogen will be released throughout the body, which is associated with an increased risk of acne, infertility, polycystic ovaries, and uterine cancer in overweight women. Abnormal amounts of SHBG also disturb the delicate balance between estrogen and testosterone, which is associated with the development of cardiovascular disease, especially in women.

“We discovered that low levels of SHBG in a person’s blood means the liver’s metabolic state is out of wack – because of inappropriate diet or something that’s inherently wrong with the liver – long before there are any disease symptoms,” says Dr. Geoffrey Hammond, the study’s principal investigator, scientific director of the Child & Family Research Institute in Vancouver, Canada, and professor in the Department of Obstetrics & Gynecology at the University of British Columbia.

“With this new understanding, we can now use SHBG as a biomarker for monitoring liver function well before symptoms arise,” says Dr Hammond, who is a Tier 1 Canada Research Chair in Reproductive Health. “We can also use it for determining the effectiveness of dietary interventions and drugs aimed at improving the liver’s metabolic state.”

Physicians have traditionally measured SHBG in the blood to determine a patient’s amount of free testosterone, which is key information for diagnosing hormonal disorders. In addition, SHBG levels are used to indicate an individual’s risk for developing type 2 diabetes and cardiovascular disease.

The discovery dispels the earlier assumption that too much insulin reduces SHBG, a view which arose from the observation that overweight, pre-diabetic individuals have high levels of insulin and low levels of SHBG. This new study proves that insulin is not to blame and that it’s actually the liver’s metabolism of sugar that counts.

Source of article?

Posted: Mon Nov 12, 2007 12:31 pm
by lyndacarol
Dom--you know that I found this article very interesting!!!

What is the source of this article? Might you be able to tell me how to get access to the original Journal of Clinical Investigation material mentioned here?

Posted: Mon Nov 12, 2007 12:50 pm
by Lyon
H Lynda,
Forget this "sugar" crap and join me on the "dark" side with the parasites!

If you really MUST persist:
http://www.jci.org/current.shtml
It says it's a freely accessible journal and I was able to view, what I THINK is the article...

The central melanocortin system directly controls peripheral lipid metabolism
J. Clin. Invest. 2007 117: 3475-3488. First Published on September 20, 2007; 10.1172/JCI31743 [Abstract] [Full Text] [PDF]

Bob

Thanks, Bob

Posted: Mon Nov 12, 2007 2:15 pm
by lyndacarol
With your help, Bob, I got to the Journal of Clinical Investigation, but by the way, the research article is:

ONLINE FIRST PUBLICATION:
David M. Selva, Kevin N. Hogeveen, Sheila M. Innis, and Geoffrey L. Hammond
Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene
J. Clin. Invest., Nov 2007; doi:10.1172/JCI32249

Thank you, friend.

(You know I can't give up the insulin angle--I have a reputation to uphold!)

Re: Thanks, Bob

Posted: Mon Nov 12, 2007 2:51 pm
by Lyon
lyndacarol wrote:(You know I can't give up the insulin angle--I have a reputation to uphold!)
OK, I guess. To each, her own :roll:

This might be the time to do a lot of reading and downloading. I was just over at Art's site and it says that Sage publishing is allowing free access this month. Sage's journals include the journal "Multiple Sclerosis", so search "insulin multiple sclerosis" to your widdle heart's content http://www.acceleratedcure.org:8080/node/2966

(when given the choice of html or pdf, save the pdf because they're self contained. Bookmarking won't be good enough because you won't be able to access them next month).

Bob

Posted: Mon Nov 12, 2007 4:08 pm
by gwa
Women tend to avoid fats and go towards low fat things to eat. The problem with low fats is that they usually contain added high fructose corn syrup and other carbohydrates to mask the crappy taste of low fat foods.

Yogurts are one example of many foods that women eat that are drained of fat and sold as low fat or not fat while containing a lot of added sugar.

Is it possible that the increase in female with MS is due to overeating high sugar diets while trying to cut down on fats? Seems to me that the incidence of MS increase in women is also tied to the introduction of the guidelines for eating a low fat diet.

Men aren't as concerned with eating low fat foods and they may be getting less sugar as a result and therefore less MS.

gwa

gwa

Posted: Wed Nov 14, 2007 6:23 am
by TwistedHelix
Hi Lynda,
I hoped you'd like that! The article you found did seem to be the full version of what I had posted, although it isn't what I had originally read. Interesting, isn't it?
Bob,
I feel the good in you, father! I'm sorely tempted to join you with the parasites on the dark side, but I don't want to condemn those poor, defenceless little creatures when I suspect they may have other accomplices like hormones, diet, stress etc.. The road to MS has many lanes. Complicated it is.
gwa,
That's an excellent point: I think with every scare story that comes along we try to process the latest " baddie" out of our food, and end up either adding something worse or removing something good. That's why I made the decision to remove as much processed food and non organic ingredients from my diet as I can, although I haven't gone overboard because I think I'm too late-stage for it to make that much difference. If I was recently diagnosed I think I'd be more evangelical about it,

Posted: Wed Nov 14, 2007 1:35 pm
by Lyon
TwistedHelix wrote:I'm sorely tempted to join you with the parasites on the dark side, but I don't want to condemn those poor, defenceless little creatures when I suspect they may have other accomplices like hormones, diet, stress etc..
Hi Dom,
I should have stayed out of that one but I just love to pick on Lynda!

I've got all I can handle with the argument that the loss of evolutionary normal conditions was the source of immune dysfunction. I'm trying to wean myself from speculating regarding whether or not experiencing some part of evolutionary normal conditions in adulthood could ever amount to a cure.

What I will say, is that despite a major factor of the hygiene hypothesis dictates that exposure during childhood "trains" your immune system to behave correctly through the rest of life (in the "wild" children are much more parasitized than adults) and that exposure in adulthood could be considered "too" late to do any good, it should be an eye opener that adults with MS found better results from parasite infestation than our best "medically accepted" treatments.

Unlike anything else in the history of MS research, "helminth immunomodulation" isn't part of the normal "throwing everything in the broom closet at MS with the hopes that sooner or later you'll run across something which shows positive results". In this case, the positive results caused researchers to look into it.

Not that one coincidental situation makes my case, but doesn't it seem more than a little coincidental that MS researchers and hygiene hypothesis researchers independently arrived at the age of 14 or 15 as a turning point over a decade before anyone considered allergy, asthma and autoimmunity to be related?

MS research lore:if you are raised in an area of low MS incidence and don't migrate to a high incidence area until after age 15, you carry the low incidence risk through life.

Hygiene Hypothesis lore: If you experience "evolutionary normal conditions" through the age of 15, your immune system is able to mature or "learn" to behave correctly through life.

C'mon over to the wild side baby........I mean, the DARK side 8)
Bob

Sugar, Testosterone and Estrogen

Posted: Wed Nov 14, 2007 7:23 pm
by Shayk
Dom

Just wanted to add my thanks as well for this very interesting info and to you also Lynda Carol and Bob for the article reference. I haven't read it yet but definitely will. That sugars impact hormone levels certainly seems relevant to me.

I'm so glad and really appreciate Dom that you're able to capture the essence of this and other research in a way I can understand.

Take care

Sharon

Posted: Thu Nov 15, 2007 6:56 am
by TwistedHelix
Hello Dark Lord, (I mean Bob),
I am very, VERY convinced by the hygiene hypothesis, but there's just one small question mark which you describe exactly: why isn't it too late after the age of about 15? I have heard of some adults with chronic asthma experiencing what amounts to a "cure" after exposure to parasites, (remember the guy who walked barefoot through latrines?), but the fix isn't permanent and re–exposure is often necessary so I just wonder if there's something else during childhood which establishes the immune system change permanently for life, (hormones, diet etc. – all the usual suspects). After all, not every child who lives free of parasites will go on to develop disease, so I'm guessing that there must be some other contributing factor.
Sharon,
I'd love to take the credit for my original post but I'm afraid not all the words were mine. I don't know why, but the formatting buttons, (quote, Italics etc.), don't seem to be working correctly at the moment. If ever you see the word "oestrogen" in my posts with the American spelling, you'll know I've lifted it from somewhere else!

Posted: Thu Nov 15, 2007 2:20 pm
by Lyon
Hi Dom,
TwistedHelix wrote:I am very, VERY convinced by the hygiene hypothesis, but there's just one small question mark which you describe exactly: why isn't it too late after the age of about 15?
What we are seeing involves two completely different situations.

1. Evidence leading to the postulation of the hygiene hypothesis pointed towards "evolutionary normal" conditions before puberty "teaches' or "matures" the immune system, so that in adulthood your immune system behaves appropriately, even without the presences of parasites. I think a "proof" is to be found in the difference in incidence between developed and non developed populations.

2. The other situation we are familiar with involves adults who hadn't experienced "evolutionary normal" conditions pre puberty and had developed immune dysfunction in adulthood and were then exposed to parasites.

#2 is among the reasons that I point out that the alleviation or opposite of the cause is not always the cure. Considering that one of the key factors of the hygiene hypothesis is enabling a "mature" immune system for entrance into adulthood, it's not expected, or fair to expect to be able to "teach" the immune system after adulthood. When I said that we were lucky that helminth treatment worked on adults already experiencing immune dysfunction, I meant that we were lucky to have found positive results and not that the adult immune system could be trained at that point, ie: one time treatment.
TwistedHelix wrote: I have heard of some adults with chronic asthma experiencing what amounts to a "cure" after exposure to parasites, (remember the guy who walked barefoot through latrines?), but the fix isn't permanent and re–exposure is often necessary
One thing that has become eminently clear is the inadequacy of the terms "cure" and "disease". They are so vague and all encompassing as to be absolutely worthless in what we would like to use them for. I use the word "cure" about 15 different ways, you and everyone else does and none of us have any way of knowing what the other means when they use it. Considering your above use of the word "cure", I again argue that he was an adult, already experiencing immune dysfunction. He did experience positive results but because of reasons mentioned above, at this point it's unfair to expect the opposite of the cause to be the cure in this case (if "cure" is considered to be a one time treatment.

Further muddying the situation, for someone trying to understand, is the fact that the T trichiura (human whipworm) lives up to 20 years in humans......providing the "cure" for 20 years. For someone 70 years old that would assuredly be a "lifetime" treatment, but through the rest of their lifetime they would have parasites controlling their immune system, as opposed to someone who had experienced evolutionary normal conditions and wouldn't need parasites in their system to avoid immune dysfunction.
TwistedHelix wrote: so I just wonder if there's something else during childhood which establishes the immune system change permanently for life, (hormones, diet etc. – all the usual suspects). After all, not every child who lives free of parasites will go on to develop disease, so I'm guessing that there must be some other contributing factor.
My above arguments have pretty much answered this to the best of my ability. With that said, I think it's a situation involving what I can't help but think of as a "predominant" predisposition. One key factor without which it would be impossible for the disease process to start, and after that other factors come into play. It's important to always realize that the only view we've ever had of MS is AFTER it's started, so we're seeing evidence of all the factors and makes it seem like stopping the disease involves some nightmare situation of having to know and correct multiple different factors, when in reality we only need to reverse the key factor.

Have I mentioned that those who cannot learn from history are doomed to repeat it? :lol: Just keep in mind the long frustrations involved in the search for the causes of the vitamin deficiency diseases and that those people were convinced that the cure HAD to be terribly complicated. Now think about how many lives could have been saved by eating an orange.

Judging by the odds, which in the absence of fact otherwise, is the best way to go, MS is not as complicated as it has always "seemed". Despite initiation of and adherence to the peer review process, which was found necessary to get MS research away from what "seemed" to be logical, MS research is still primarily driven by what "seems" and what has "seemed".

Yours truly,
Darth

Posted: Fri Nov 16, 2007 8:04 am
by TwistedHelix
Hello DV,
I absolutely see and accept your points: the immune system does not learn after puberty but merely responds to the controlling efforts of parasites, and I think all of us use the word "cure" as convenient shorthand for all of the ifs, buts and maybes which encompass potential treatments, therapy or prevention of MS.
What I am trying to understand is what exactly defines " maturity" in the immune system? What is it that stop or starts during puberty which prevents the immune system from learning lifelong lessons afterwards? Sex differences in autoimmune diseases only show at or after puberty, (Basic and Clinical Endocrinology, Greenspan and Gardner), and there are strong indications that sex hormones have a direct influence on the immune system, ("Various lines of evidence suggest that immunological responses and sex steroid hormones are linked at physiological and cellular levels" – from "The Maturing Immune System" by Heather B. Jaspan; Stephen D. Lawn; Jeffrey T. Safrit; Linda-Gail Bekker), so I'm inclined to believe that it is the hormonal effects of puberty, such as changes in the thymus, which are responsible. There are even sex and age differences in the response to vaccines: for example, responses to the BCG vaccine vary according to pubertal stage and testicular volume, and even the timing in the menstrual cycle can have an effect, (same source).
I am further convinced because the thymus involutes, (atrophies), in response to testosterone, and since this is where T cells mature and some autoreactive cells are deleted, it could partly explain this loss of learning function.
We are in absolute agreement that the root cause of MS is very likely to be a single, perhaps simple event,(like missing helminths), and that the opposite of cause is not necessarily cure, but until we are able to cut it out at the root it is my hope that interrupting some of the events which occur later on in this ghastly, complicated chain, we might find a way to ameliorate some of its effects,

Posted: Fri Nov 16, 2007 1:52 pm
by Lyon
Hi Dom,

http://www.nbc10.com/video/4566179/index.html

There are a multitude of examples showing that, system wide, youth is an evolutionized time of learning. Us "old dogs" can learn, but in many aspects of the human system, any time after adolescence is just "too late". I'm not saying that it's impossible to work around that situation, but things get harder at that point.
TwistedHelix wrote:I am further convinced because the thymus involutes, (atrophies), in response to testosterone, and since this is where T cells mature and some autoreactive cells are deleted, it could partly explain this loss of learning function.
The aspect of where the immune system's education is "stored" and what mechanism signals the end of the immune system's adolescent education is interesting, but is something I've never considered before and I can't even speculate, although it's coincidental that you mention the thymus because think in the past, you and I have discussed other reasons to suspect the thymus.

Bob