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Dr. Bob is Robert Hsiung, MD,
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Posted by raybakes on November 29, 2004, at 6:30:58
Was looking up the effects of horny goat weed (epimedium) after I tried it and felt wonderful. Found it reduces an inflammatory chemical called interleukin 6 that is involved osteoporosis...think interleukin 6 also regulates tsh, acth and vasopressin.
Role of Interleukin-6 and Its Receptors in the Osteoporosis of Sex-Steroid Deficiency
The production of interleukin-6 by cells of the stromal-osteoblastic lineage is inhibited in vitro by estrogen and androgen [51,75] through receptor-mediated actions on the transcriptional activity of the interleukin-6 gene promoter [51,76-78]. Conversely, estrogen loss results in increased production of interleukin-6 by ex vivo bone marrow cell cultures, and increased production of interleukin-6 follows the withdrawal of estradiol from primary cultures of calvarial cells [79]. In agreement with in vitro evidence, circulating levels of interleukin-6 are elevated in estrogen-deficient mice, rats, and humans [74]. Direct support for the contention that interleukin-6 is responsible for increased bone resorption after loss of sex steroids is derived from studies showing that injections of an interleukin-6-neutralizing antibody in female or male mice that have had gonadectomy prevents the increase in osteoclastogenesis in bone marrow and the increase in the number of osteoclasts in sections of trabecular bone [51,80]. Furthermore, unlike wild-type controls, interleukin-6 knockout mice do not show cellular changes in the marrow and trabecular bone sections and are protected from the loss of trabecular bone after the loss of sex steroids [48,51].
Posted by raybakes on November 29, 2004, at 6:39:43
In reply to osteoporosis and hormones, posted by raybakes on November 29, 2004, at 6:30:58
and a bit more...
Integration of the Immune and Endocrine Systems by Interleukin-6
Dr. George P. Chrousos (Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH): The stress system has a central nervous system component and a peripheral component [95]. The central component consists of the hypothalamus, which includes corticotropin-releasing hormone and vasopressin neurons of the paraventricular nucleus, and the brain stem, which includes the noradrenergic neurons of the locus ceruleus and other autonomic centers. The peripheral component consists of the hypothalamicpituitary-adrenal axis and the peripheral autonomic nervous system, which also includes the adrenal medullae. Activation of the stress system leads to suppression of the growth and reproductive axes [96], alterations in thyroid function recognized in the euthyroid sick syndrome [40], and suppression of the immune-inflammatory reaction associated with a shift from the Th1 to the Th2 profile [97].
Interleukin-6 has a profound stimulatory effect on the stress system [20-22] and is secreted when the system is activated during inflammatory [98,99] and (to a lesser extent) noninflammatory stress [25,35,36,100]. Interleukin-6 may play a pathogenetic role in conditions related to chronic stress and physiologic aging. Aging is characterized by progressively increasing concentrations of glucocorticoids and catecholamines and decreasing production of growth and sex hormones, a pattern reminiscent of that seen in chronic stress (Figure 4). Recent studies [101,102] have shown that plasma levels of interleukin-6 increase with age, probably as the result of catecholamine hypersecretion and sex-steroid hyposecretion, and that interleukin-6 levels correlate with the functional disability of elderly persons [103]. Therefore, interleukin-6 may contribute to the increased morbidity and mortality seen in chronically stressed or physiologically aging persons. The potential involvement of interleukin-6 in the pathophysiology of aging and chronic stress calls for research on ways to suppress its secretion or effects.
Posted by raybakes on November 29, 2004, at 6:46:53
In reply to Re: osteoporosis and hormones » raybakes, posted by raybakes on November 29, 2004, at 6:39:43
'Epimedium (horny goat weed) can inhibit the expression of IL-6 mRNA, which may contribute to its anti-resorptive effect.'
Posted by Tabitha on December 1, 2004, at 0:33:40
In reply to and how to inhibit it.... » raybakes, posted by raybakes on November 29, 2004, at 6:46:53
Wow. I want to take it just so I can go to the store and ask for "horny goat weed".
Thanks for the info. All the reports about preventing osteoporosis are so confusing. I'm not sure what to do besides take calcium supplements.
Posted by raybakes on December 1, 2004, at 12:26:47
In reply to Re: and how to inhibit it.... » raybakes, posted by Tabitha on December 1, 2004, at 0:33:40
> Wow. I want to take it just so I can go to the store and ask for "horny goat weed".
>
> Thanks for the info. All the reports about preventing osteoporosis are so confusing. I'm not sure what to do besides take calcium supplements.Interleukin 6 isn't all bad, only in excess - too low is bad as well. It's an indication that the body has excess inflammation, that's the real problem, but reducing it can help.
It is really confusing reading the reports about osteoporosis as they do contradict.
Estrogen protects bone by blocking the action of interleukin 6...
"The major physiological effect of estrogen is to block activation of the bone metabolic unit. Estrogen effects may be mediated in part by growth factors and interleukins. For example, interleukin 6 is a potent stimulator of bone resorption, and estrogen blocks the osteoblast's synthesis of interleukin 6. Estrogen may also antagonize the interleukin 6 receptors. Transgenic mice without interleukin 6 do not develop osteoporosis after oophorectomy."
Also found this interesting as it shows high dairy intake can increase the chance of hip fractures in the elderly - can too much calcium cause osteoporosis - most studies use bone mineral density as an indicator, but it may not be appropriate, except to sell dairy products!
"Dairy-product intake and hip fracture among older women: issues for health behavior"
and vitamin D is important as well...
Ray
Posted by tealady on December 1, 2004, at 13:57:08
In reply to Re: and how to inhibit it.... » raybakes, posted by Tabitha on December 1, 2004, at 0:33:40
The main thing is exercise..preferably load bearing(like walking maybe with a pack on)..with a small to moderate dairy diet if possible too. (like milk on brekkie, cheese occasionally, butter, small yoghurt occasionally, gotta be some in chocolate..about 1to 2 glasses milk per day total approx?)
Calcium supps are OK too but too much can maybe cause kidney stones, so dietary calcium is usually preferred..depending on how much water you drink of course(lots of water like I've been drinking is not good, but it does stop any possiblity of kidney stones, and then you need the calcium supps)
Vit D helps or preferably say 15 mins sunshine a day if warm climate, oherwise fish liver oil maybe?I got from Z=-1.75(in 30's) to Z=-1.1 on BMD's..not great I know with the above.
I think the study on BMD and hip fractures and dairy consumption may ppossibly be biased as I know that if one is questioned about dairy intake if found to have hip fracture a lot of people will tend to "up" their dairy intake in their answers..just a "protective" answer...but who knows
Otherwise keeping this IL-6 down to normal levels is the thing :-)
I'm trying to understand this now.
Jan
Posted by raybakes on December 1, 2004, at 17:10:13
In reply to Re: and how to inhibit it.... Raybakes » Tabitha, posted by tealady on December 1, 2004, at 13:57:08
> >
> I got from Z=-1.75(in 30's) to Z=-1.1 on BMD's..not great I know with the above.
>
> I think the study on BMD and hip fractures and dairy consumption may ppossibly be biased as I know that if one is questioned about dairy intake if found to have hip fracture a lot of people will tend to "up" their dairy intake in their answers..just a "protective" answer...but who knows
>
> Otherwise keeping this IL-6 down to normal levels is the thing :-)
> I'm trying to understand this now.
>
>Hi Jan, just wonder if there's something missing in the equation as I keep seeing abstracts like this..
'Fractures, calcium, and the modern diet.'
"Why do populations who consume low-calcium diets have fewer fractures than do Western societies who consume high-calcium diets?"
Just worry that the dairy industry and drug companies are pushing research one way when the answers are perhaps more subtle? Could be wrong, but I love a mystery!
ray
Posted by raybakes on December 1, 2004, at 17:24:09
In reply to Re: and how to inhibit it.... Raybakes » Tabitha, posted by tealady on December 1, 2004, at 13:57:08
and this abstract shows some good data...
as a risk factor for fractures in women in asia, low calcium intake was a risk factor of 2, use of sedatives was a risk factor of 2.5, high alcohol 2.9, low excercise in youth 7.2, and thyroid drugs 7.1
'Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study.'there may be confounding factors between different societies but medication, alcohol and low excercise appear to be large risk factors.
Ray
Posted by tealady on December 1, 2004, at 18:46:32
In reply to Re: and how to inhibit it.... Raybakes » tealady, posted by raybakes on December 1, 2004, at 17:24:09
> and this abstract shows some good data...
>
> as a risk factor for fractures in women in asia, low calcium intake was a risk factor of 2, use of sedatives was a risk factor of 2.5, high alcohol 2.9, low excercise in youth 7.2, and thyroid drugs 7.1
>
>
> 'Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study.'
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11277276
>
> there may be confounding factors between different societies but medication, alcohol and low excercise appear to be large risk factors.
>
> RayHi Ray,
Re Thyroid meds:
it appearas that IL-6 is probably the issue here again
Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism
Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not decrease in euthyroid state. The lymphocyte number and ratio in differentials increased significantly in the hyperthyroid state (P < 0.001). In euthyroidism they decreased significantly (P < 0.001) but it was significantly higher than the baseline value (P < 0.05). Our findings showed that the deleterious effect on bone metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism
my comment - It's a pity they did not also retest at 12 weeks after reversal to eurothyroidism....as this is when they say that typically the hypothalmic/piuitary feedback are usually normalised
--------------------------------This is one of my many "look into sometime " articles.
I'm on thyroid meds too..but so far have kept levels much the same(Z=-1.1 to Z=-1.2 over 3 years) ..with a lot of hard work..pretty disappointing actually.also
-------------------
Interleukin-6 production and secretion by human parathyroids
Clin Exp Immunol. 2004 Apr;136(1):145-56.
PMID: 15030526 [PubMed - indexed for MEDLINE]Parathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption
________________________________
so it looks to me like IL-6 may "possibly" be the thing that causes the bone resorption..and thyroid hormones(T3 , T4) increase IL-6 if thyroid hormone levels are allowed to get too high as in hyperthyoid.
-----------
Jan
Posted by tealady on December 2, 2004, at 2:07:29
In reply to Re: and how to inhibit it.... Raybakes » tealady, posted by raybakes on December 1, 2004, at 17:10:13
> > >
> > I got from Z=-1.75(in 30's) to Z=-1.1 on BMD's..not great I know with the above.
> >
> > I think the study on BMD and hip fractures and dairy consumption may possibly be biased as I know that if one is questioned about dairy intake if found to have hip fracture a lot of people will tend to "up" their dairy intake in their answers..just a "protective" answer...but who knows
> >
> > Otherwise keeping this IL-6 down to normal levels is the thing :-)
> > I'm trying to understand this now.
> >
> >
>
> Hi Jan, just wonder if there's something missing in the equation as I keep seeing abstracts like this..
>
> 'Fractures, calcium, and the modern diet.'
>
> "Why do populations who consume low-calcium diets have fewer fractures than do Western societies who consume high-calcium diets?"
>
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11684522
>
> Just worry that the dairy industry and drug companies are pushing research one way when the answers are perhaps more subtle? Could be wrong, but I love a mystery!
>hmmm well I'm getting slightly tired of too many mysteries...overwhelmed I guess
Definitely the dairy industry is pushing and powerful!
The Z=-1.75 was on a good diet of veges, fruit, high meat, wholegrains..no junk, no artifical colors, flavors, preservatives..exercised as teenager until mid 20's ..about 10 years after, feeling very hypothyroid in symptoms.
(in case anyone doesn't know, Z of less than -1.0 is osteopenia and Z=-2.5 is where you fracture hips etc..not good for someone then in their 30's.)
Ray, do you think that for someone with a light build..say 50kg most of their life(although 45kg up to about 30) that a Z=-1.75 is still like "normal"? I mean I know there is a difference in bone density and a Z of 1 is only 1 standard deviation, so do you think that maybe I was normal in bone density anyway?
It seemed a bit too far out to me.
For all I know I may have been hyperthyroid earlier in life and then I may have lost bone density due to the excess thyroid hormones..it's possible from symptoms.3 years earlier than the test in my 30's for BMD where I gt a Z=-1.75, had slightly raised TSh=3.6...but untreated.
Had up to that time tried soy and low dairy...also tried hypoglycemic diet, small meals about 5 a day with pritikin type diet and something closer to "cave-man type diet " these days for a years...
Did test out as hypoglycemic..both types(relative and absolute) about age 30, but didn't get any better after years of diet.all I did to get the BMD up was take a calc/mag most nights and increase dairy slightly.
I do have a problem in that I drink now(and all my life) too much water..so I guess increased calcium consumption was needed to keep my blood levels up (as with everything)
After starting on thyroid hormones which increased metabolism, I needed to supplement on all salts even more as the thyroid hormone ncreases one's metabolism.
If you are low on calcium in the blood, your body just extracts the needed calcium from the bone.
It's been a while since I looked but I did gather at the time that high dairy was bad..like over 2 glasses milk /day equivalent..and low to moderate seemed to be best from the studies I read...but as you say...dairy industry has big interest and funding for a lot of these studies. It may have been just the calcium supps I guess. I was already eating healthily..even to the point during those years of growing own veges organically etc...making own soy milk at one stage even
I was definitely going downhill without calcium supps in some form.
Got my blood tests back today.
My calcium levels are finally great. I've been having a break at present from supps but not as yet from the dairy.
I achieved this but drastically cutting water intake to 4 Litres a day..need to reduce to 3 litres a day sometime.
Actually cutting back to 4L and cutting all salts to normal levels..all my levels of all electroyltes are finally good...so it was the excess water I was struggling with.
Even albumin has came up to a good level..was too low!
Problem is I'm still very thirsty and have just temporarily stared drinking again, sigh...very hot weather.
Jan
Posted by raybakes on December 3, 2004, at 6:04:21
In reply to calcium and osteoporosis??.... Raybakes » raybakes, posted by tealady on December 2, 2004, at 2:07:29
> all I did to get the BMD up was take a calc/mag most nights and increase dairy slightly.
>
> I do have a problem in that I drink now(and all my life) too much water..so I guess increased calcium consumption was needed to keep my blood levels up (as with everything)
>
> After starting on thyroid hormones which increased metabolism, I needed to supplement on all salts even more as the thyroid hormone ncreases one's metabolism.
>
> If you are low on calcium in the blood, your body just extracts the needed calcium from the bone.
>
> It's been a while since I looked but I did gather at the time that high dairy was bad..like over 2 glasses milk /day equivalent..and low to moderate seemed to be best from the studies I read...but as you say...dairy industry has big interest and funding for a lot of these studies. It may have been just the calcium supps I guess. I was already eating healthily..even to the point during those years of growing own veges organically etc...making own soy milk at one stage even
>
> I was definitely going downhill without calcium supps in some form.
>
> Got my blood tests back today.
> My calcium levels are finally great. I've been having a break at present from supps but not as yet from the dairy.
> I achieved this but drastically cutting water intake to 4 Litres a day..need to reduce to 3 litres a day sometime.
> Actually cutting back to 4L and cutting all salts to normal levels..all my levels of all electroyltes are finally good...so it was the excess water I was struggling with.
> Even albumin has came up to a good level..was too low!
> Problem is I'm still very thirsty and have just temporarily stared drinking again, sigh...very hot weather.
Hi Jan, didn't want to give calcium too much of a bad name! just wanted think about the bigger picture in bone metabolism. There was one theory that the osteoblasts can prematurely age if we have too much calcium in our lives, so that even if we have sufficient calcium, there aren't enough healthy osteoblasts to repair the microfractures from normal excercise. Looking at a lot of the articles, it might be the quality of the bone matrix rather than the quantity that might be important.
Good luck with the water intake!
Ray
Posted by Larry Hoover on December 10, 2004, at 11:00:30
In reply to Re: and how to inhibit it.... Raybakes » tealady, posted by raybakes on December 1, 2004, at 17:24:09
> and this abstract shows some good data...
>
> as a risk factor for fractures in women in asia, low calcium intake was a risk factor of 2, use of sedatives was a risk factor of 2.5, high alcohol 2.9, low excercise in youth 7.2, and thyroid drugs 7.1
>
>
> 'Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study.'
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11277276
>
> there may be confounding factors between different societies but medication, alcohol and low excercise appear to be large risk factors.
>
> RayThis one shows other risk factors, and none for calcium intake:
Int J Epidemiol. 1995 Aug;24(4):771-82.
Diet and hip fracture risk: a case-control study. Study Group of the Multiple Risk Survey on Swedish Women for Eating Assessment.
Michaelsson K, Holmberg L, Mallmin H, Sorensen S, Wolk A, Bergstrom R, Ljunghall S.
Department of Orthopaedics, Central Hospital, Vasteras, Sweden.
BACKGROUND. The role of diet as a risk factor for osteoporotic fractures is unclear. Earlier studies have yielded conflicting results. METHODS. In two counties in central Sweden we investigated the association between dietary intake and the risk of proximal femoral fractures in a case-control study nested in a cohort. Women born in 1914-1948 were asked to fill out a food frequency questionnaire when invited to attend for mammographic screening between the years 1987 and 1990. More than 65,000 women completed the questionnaire. Those who had participated in the enquiry and subsequently sustained a first hip fracture were defined as cases. For every case, four individually matched controls, by age and county of residence, were selected from the cohort. A second questionnaire concerning confounding factors was mailed to controls and cases. In all, 247 cases and 893 controls could finally be included. Monthly intake of foods and daily intake of nutrients were calculated. RESULTS. When highest quartile of intake was compared to lowest, intakes of iron (adjusted odds ratio [OR] of 3.3, 95% confidence interval [CI]: 1.6-6.9), magnesium (adjusted OR = 2.7, 95% CI: 1.3-6.0) and vitamin C (adjusted OR = 1.9, 95% CI: 1.2-3.1) were found to be independent risk factors for hip fracture. High calcium intake did not protect against hip fracture. Smoking, low physical activity in leisure time, low body mass index, earlier fracture of the distal forearm and diabetes were all risk factors while postmenopausal hormone replacement therapy protected against hip fracture. DISCUSSION. This large study indicates new dietary risk factors for hip fracture. The association between high dietary intake of iron, magnesium and vitamin C and risk of hip fracture has not been reported previously. Further clinical and experimental studies are needed to confirm these findings and to investigate their mechanism of action.
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