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Pipistrelle
inactive member
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Posted: Fri Jan 28th, 2011 00:09 |
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Dr Marshall,
 to the Telmisartan experiment. But thank you! I hope it didn't knock you off for too long...
Pipistrelle
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Sarc lungs, uveitis '90 dx '92, pred 18 mo '93-'94; D25 31 Nov 06, D1,25 35 Nov 06, NoIRs Feb '07, D restrict Nov 06, cover up, light exp commute 70 mins/day Mon, Tues, Wed
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Limburg
Member
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Posted: Fri Jan 28th, 2011 03:17 |
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Dr. Daredevil, brave of you, are you allright?
 Annemarie
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MP Jan.2009.Break from september 2017-december 2017. MS.1997. AIH 2004. Muscles, Joints, Skin, various symptoms. 25D=25.6(nmol/ml)september 2014.From april 2016; blood and protein in urine. Skinrashes, several allergies.
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Phillyguy
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Posted: Fri Jan 28th, 2011 05:04 |
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Expert opinion on drug safety. 2011 Jan 23;
Safety and efficacy of olmesartan: an observational pooled-analysis of 156,682 hypertensive patients.
Scholze J, Schäfer A, Kreutz R
Background: Angiotensin type 1 receptor blockers are recommended for first-line antihypertensive treatment. Methods: We performed a pooled-analysis of 20 post-authorization surveys of olmesartan involving 156,682 hypertensive patients. Olmesartan was used as monotherapy or in combination with other antihypertensive drugs, for example, hydrochlorothiazide. Objectives: We assessed the safety of olmesartan by monitoring adverse drug reactions (ADRs). The number of patients achieving systolic and diastolic blood pressure (BP) targets (< 140/90 mmHg in the overall population, < 130/80 mmHg in high-risk patients) or responding to treatment (BP decrease of ≥ 20/10 mmHg) was also determined. Results: In all, 43.8% of patients received olmesartan monotherapy, 29% olmesartan with hydrochlorothiazide and 27.2% olmesartan in combination with other antihypertensives. The frequency of ADRs was 0.4% and not altered by dose, age ≥ 65 years or presence of co-morbidities. About 90% of patients were responders. Blood pressure targets were achieved in 52.8 and 35.7% of patients without risk factors and in the overall cohort, but only in 8.1 and 27.5% of patients with renal dysfunction or taking NSAIDs. Conclusion: Olmesartan was very well tolerated. Responder rates to olmesartan were high, although BP targets were only achieved in a minority of patients at high risk, with renal dysfunction or taking NSAIDs.
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Prof Trevor Marshall
Foundation Staff
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Posted: Fri Jan 28th, 2011 05:54 |
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Limburg wrote: Dr. Daredevil, brave of you, are you allright? Annemarie
It was a long time ago, Annemarie. I tried the other ARBs too, just to make sure my in-silico results were roughly in line with what could be observed in-vivo.
I still check out potential IP-modifying drugs today. All have had major side effects...
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Limburg
Member
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Posted: Fri Jan 28th, 2011 07:18 |
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Okay Dr. Marshall, so are you okay  ?
You still are a daredevil, even more, since you try so many ARB's 
Have a nice weekend,
Annemarie
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MP Jan.2009.Break from september 2017-december 2017. MS.1997. AIH 2004. Muscles, Joints, Skin, various symptoms. 25D=25.6(nmol/ml)september 2014.From april 2016; blood and protein in urine. Skinrashes, several allergies.
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Grateful Survivor
Support Team
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Posted: Fri Jan 28th, 2011 16:45 |
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| Amazing...
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MP Feb'07 (no breaks)| Lyme '98, Arrhythmia-Tachy-Vertigo '06, Appendicitis-Colon-Resection '89, Bipolar '83, Meningitis '47 | my progress | last 25D= 9ng/mL Aug'16
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Bane
Research Team
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Posted: Fri Feb 11th, 2011 00:25 |
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Blood Pressure Meds May Lower the Risk of Cancer, Study Finds
http://www.aolhealth.com/2011/02/04/blood-pressure-meds-cancer-risk/
"Even more surprising: The longer patients were on the medications, the better their chances of avoiding cancer, with those on ARBs for a year or more having a 50 percent lower risk, according to The American Journal of Cardiology findings"
"To me, it's very clear, but other groups have suggested the jury is still out on this topic," Sipahi said.
Guess he is still convinced Telmisartan cause cancer?
Last edited on Fri Feb 11th, 2011 00:47 by Bane
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Bane
Research Team
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Posted: Tue Mar 1st, 2011 14:04 |
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Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals
http://tiny.cc/c1cdp
Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks.
Objective: Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants.
Patients and methods: Individuals at high CVD risk were randomized to telmisartan (three trials, n = 51 878), irbesartan (three trials, n = 14 859), valsartan (four trials, n = 44 264), candesartan (four trials, n = 18 566), and losartan (one trial, n = 9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n = 42 403), the ARBs were compared to ACEi and in 11 trials (n = 63 313) to controls without ACEi. In addition, in seven trials (n = 47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n = 25 712).
Results: Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.
Conclusion: There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.
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Prof Trevor Marshall
Foundation Staff
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Posted: Tue Mar 1st, 2011 14:12 |
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By considering ARBs as a class of drugs, this study has drawn the wrong conclusions. I would be very surprised if Telmisartan alone exacerbated the long-term risk of cancers, as it suppresses VDR-mediated inflammation.
Then again, maybe the studies just didn't run for long enough to see the cause and effect relationships
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Phillyguy
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Posted: Tue Mar 1st, 2011 19:15 |
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Would't one also expect that people who are on ARBs in the first place probably have higher baseline systemic inflammation and are therefore probably more prone to develop cancers?
Its also important to consider that while some drugs may exert anti-proliferative effects in target tissue, they may also have similar anti-proliferative effects on certain aspects of the immune system.
An example of this would be the mtor inhibitors - immuno-suppressants with paradoxical anti-viral and anti-cancer effects. They work well in cell culture (anti-cancer effects in target tissues) but are associated with increased cancer in vivo (block proliferative ability of immune system). Mtor fuels cancer growth but is also required for an optimal cytotoxic adaptive response. Kind or a trade-off. This is my primary concern with 'longevity drugs' like resveratrol and rapamycin.
Its possible that the ARBs are similar in this regard. Anti-proliferative (in target tissue but also the immune system). It seems to me that if you are taking a drug that inhibits the adaptive response by inhibiting cytokinesis (All ARBs), its probably also a good idea that the drug exert anti-proliferative effects in target tissues (olmesartan).
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Prof Trevor Marshall
Foundation Staff
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Posted: Tue Mar 1st, 2011 22:25 |
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Phillyguy,
mTOR is at the heart of dozens, perhaps hundreds, of biological pathways. A lot of studies have been done in mice on mTOR, yet it was not obvious to me that the mouse studies will directly translate to humans. Since mTOR is short for "Mamalian Target of Rapamycin," and Wikipedia seems to consider the drug Rapamycin to be immunosuppressive, I have personally taken the drug on two separate occasions to see what its effects might be for people on the MP.
My assessment is that any of our members who take Rapamycin run the risk of their IP becoming totally unstable, and becoming very ill indeed. In my case, the postural hypotension that has been gone these past few years came back with a vengeance, general IP and malaise increased, and trying to wean was very difficult (and painful) with high vascular permeability (quite powerful migraines) and an overall IP surge..
Please stay away from mTOR inhibitors like Rapamycin. Even at quite low doses they affect the human body in far more profound ways than the more common corticosteroids, which have also proved to be dangerous. I fear the emphasis on Rapamycin and mTOR in the media might tempt MP members to experiment, members whose bodies are still too ill to withstand the cardiovascular effects of this drug.
It is important to understand that what you read in PubMed is written by people who (largely) have little idea what they are doing. They are trying to elucidate some individual pathway which interests science. Not one is looking for a cure (well, very few, anyway). They are looking for drugs which will make them famous and rich (sadly, this is what drives many research biologists these days). They tend to overlook potential risks from the drugs they are exploring.
It is also important to remember that "the overall death rate from Sarcoidosis is only 5%," well, at least that is what Clinical Medicine will tell you. You see, deaths from heart failure, stroke, liver failure, cancers, and other systemic maladies could not be due to the Sarcoidosis, as Medicine considers Sarcoidosis as a lung disease 
In other words, medical specialization tends to hide dangerous drug side-effects. Sarcies dying of cancer, heart-attack, etc are not determined to die from the Sarcoidosis, but from "another disease." Medicine buries its mistakes. When people are adversely affected by a complex drug like Rapamycin, I am sure that very few of the deaths are logged as being due to the drug...
I keep my eye open for anything which might help members recover more quickly, with less pain, or less disruption of lifestyle. But many of our members are desperate for quick solutions. Before posting about new drugs in future, why not drop me a note and see what I (and my colleagues) already know about it? There may be "primary concerns" that we already know about.
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appledrummer
member
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Posted: Thu Mar 10th, 2011 03:10 |
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http://www.nejm.org/doi/full/10.1056/NEJMoa1007994
"The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern." They only used 40mg once a day.
Physicians First Watch notes: "An editorialist writes that the finding of delayed microalbuminuria was not unanticipated. And given the increased cardiovascular mortality found with olmesartan, she asks why wouldn't other renin-angiotensin blocking drugs be prescribed if they are not associated with fatal complications?"
Why wouldn't they?? Huge assumptions/simplifications!
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Dx Fibromyalgia syndrome,depression w/chronic fatigue, photosensitivity. 2007/08 Cut D intake, NoIRs, avoided light. Started MP 2009. Stopped 2011. Restarted mid 2012 Olmesartan 4hrly, now plus NAC & cortef. Recovered better health
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roelof
Member
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Posted: Thu Mar 10th, 2011 21:34 |
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Hello,
I looked at the article, but the differences are hardly statistical relevant. I am used to take technical decisions. To draw conclusions from less than 10% difference in this test is less than 2 sigma. I probably have to become used to medical practice.
When you go to your doctor you hope to get a 99% sure cure, and not well it did 0.7% better than the other cure. But both did not help a big number of people.
Best regards Erik
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MP start Feb'11 (no breaks) | Sarcoidosis '10, hypertension '05 | lungs, heart, foot pain, hand pain, cognitive | last 25D= 4 ng/mL april 2014
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seanlane
Member
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Posted: Sat Mar 12th, 2011 08:14 |
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Trevor wrote~
My assessment is that any of our members who take Rapamycin run the risk of their IP becoming totally unstable, and becoming very ill indeed. In my case, the postural hypotension that has been gone these past few years came back with a vengeance, general IP and malaise increased, and trying to wean was very difficult (and painful) with high vascular permeability (quite powerful migraines) and an overall IP surge..
Wow...besides the obvious conclusion that this is dangerous for the MP, what other thoughts do you have as to why these reactions may have occurred?
It's particularly interesting as curcumin also inhibits mTORC1.
When my PhD friend Steve Creacy[ on MP] experimented with curcumin he went through terrible IP and developed open lesions on his face.
It seems odd that something that is considered immunosuppressive like Rapamycin would increase or bring back old symptoms...why would it do that?
Or maybe not. Everything that I used to suppress my immune system eventually seemed to bring out more symptoms and make me sicker.
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bipolar CFS neuropathy arrhythmia food sensitivities psoriasis MCS guillain-barre tinnitus 125D58 Ph1Jul/08 Ph2Oct/08 25D=17.8 Sept/08 25D=11.8 Jul/09 Ph3 Sept/09
Lyme positive Sept 2014
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scooker48
Member*
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Posted: Sat Mar 12th, 2011 09:07 |
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Seanlake--
My ideas about bacteria, fungi and viruses are simplistic. However, it appears they can go dormant for long periods of time, and then spring forth and multiply. One study I read somewhere dated the dormancy period to 34,000 years (no joke). We apparently do not understand their life cycles.
Understanding our own immune system is the best strategy I have ever read, thanks to the MP. I too have had issues with food: cinnamon, oregano, and yes mustard. So I respectfully stay away from the substances, or suffer.
And of course, I always honestly admit that I at much cinnamon as a child and young adult. Miss Gingersnap here. And plenty of oregano in Italian cooking. And my recipe box has an old favorite for "milk and half a cup of mustard" tossed onto a pork chop, a chicken breast, or even fish. And then baked. YIKES. Obviously, I do not eat that way any more.
Thanks to this community and ARF, I think we're providing some very useful information.
"Hold the mustard".
Sherry
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D25, Total: 12 measured 11/3/15 Started MP=01/04/05 Diagnosis: Sarc 12/04; "cat scratch disease" or necrotizing graunulomas 10/88; Raynaud's (diagnosed 1980?)
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GeorgeinRollaMO
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Posted: Sat Mar 12th, 2011 09:57 |
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Sherry,
Those products, "...cinnamon, oregano, and yes mustard.", will give me cramps in my lower legs at night if I consume them now. I used to consume them in goodly amounts when younger. The one common thing between them that I have found is that they contain salicylates. I have found that all products that contain salicylates, as well as artificial food dyes and flavors, most "natural flavors" such as the spices and mints [spearmints & peppermints] will do the cramps for me, too. The only thing that I have found to counteract the affect is to take quinine sulfate [260 mg tablet for which one needs a Rx order], and that ability is limited, also. I need to restrict my intake of the salicylates, etc. Someone else's symptom(s) may be different than mine, but an affect, nevertheless, IMHO. My list of foods/drinks that I can partake is rather limited because of that.
One can obtain a listing of the salicylate contain of most foods/drinks with doing a Google search. There are three such lists that I am aware of. Two of them give just a five-degree ranking, and a third list gives a listing by quantity of the salicylate.... most foods are under a numerical amount of twenty per unit of measure. The spices are in the hundreds.
Wishing all wellness!!!
Dark Vader...aka, George
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Borreliosis:7/14/04--125D=57,25D=61. Ben 9/1/04. Mino 10/5/04. 4/13/05--125D=58,25D=43. 8/17/05--125D=52,25D=36. April 06=125D=38,25D=29. 8/29/06--125D=37,25D=29. June 07 25D=23. Oct31'07,25D=19.
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Bane
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Posted: Mon Mar 14th, 2011 04:45 |
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ROADMAP published, but no news on FDA safety review of ARB
http://www.theheart.org/article/1196817.do
Haller told heartwire, "The data [published in the journal] are the same" as were presented at the European Society of Hypertension (ESH) meeting in Oslo last summer, but some of the analyses reported there do not appear in the manuscript; "there will be follow-up publications."
The results show there was a cumulative incidence of microalbuminuria of 8.2% with olmesartan and 9.8% with placebo; the primary end point, time to onset of microalbuminuria, was delayed by 23% with olmesartan (hazard ratio 0.77, p=0.01), with the majority of this effect being BP independent.
But in ROADMAP, there were 15 cardiovascular deaths in the olmesartan group—seven cases of sudden death, five fatal MIs, two fatal strokes, and one death related to coronary revascularization—compared with a total of three CV deaths—one sudden death and two fatal strokes—in the control group (0.7% vs 0.1%, p=0.01).
Most of the excess cardiovascular mortality in the olmesartan group occurred in those with preexisting cardiovascular disease (11 events vs one with placebo, p=0.03) and among patients in the lowest quartile of BP, the investigators point out.
In contrast, fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events, 3.6% vs 4.1% (p=0.37), they note.
"The fact that these signals go in opposite directions, together with the feeling that the study was underpowered to determine cardiovascular risk, has led many to comment that these results may well be due to chance," says Ingelfinger in her editorial. Haller et al agree, and last year, at the ESH meeting, Haller told heartwire: "It's clear-cut, it's not a problem of olmesartan; we are sure about that."
Nevertheless, Haller et al now appear to be hedging their bets somewhat, admitting in their paper that the CV mortality finding is "of concern." Excessive reduction of BP in some high-risk patients may confer a predisposition to an increased risk of death, a finding that is consistent with the well-known, somewhat-controversial "J-curve-effect," they observe, pointing out that the ESH states that doctors should avoid lowering BP excessively to values below 120/70 mm Hg in people with underlying CVD.
They also concede that "a direct effect of olmesartan cannot be ruled out" and point out that the FDA is currently reviewing the existing data on the drug.
Ingelfinger adds that olmesartan has been promoted as a medication that helps patients reach BP goals rapidly and that the dose used in ROADMAP, 40 mg, was higher than that used in many other studies. In the other smaller trial being looked at by the FDA, ORIENT, 500 patients were randomized to receive olmesartan at 10 mg/day to 40 mg/day or placebo. There were 10 cardiovascular deaths in the olmesartan group compared with three in the control group.
Target those with high BP, low eGFR or albuminuria for most benefit
Haller et al say their findings extend the results of other trials and suggest that olmesartan delays the time to onset of microalbuminuria in type 2 diabetes, "even when BP control is excellent according to current recommendations."
"These results provide hope that it may be possible to prevent chronic kidney disease in the many persons worldwide who have type 2 diabetes mellitus," says Ingelfinger in her editorial.
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TikBitten
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Posted: Tue Mar 15th, 2011 19:53 |
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Dr Trevor Marshall wrote: Well, it had to happen - FDA has at last noticed that Benicar is affecting Cardiovascular disease in Th1 individuals - specifically Diabetics.
Trevor-
It would seem [at least IMO] the MP disease model and treatment protocol continues to suffer greatly at the hands of the critics, including the FDA, for the simple fact no study data has been set forth correlating increased levels of antimicrobial peptides, including β-defensins (hBDs) and cathelicidins, as having been directly up-regulated solely by the introduction of therapeutic doses of Olmesartan. Unless, of course, I missed that some where along the way?
Given the sensitivity with which metabolites, and their by-products, can so easily be detected now a days, I have often wondered how this might dampen down speculation as to the efficacy of Olmesartan in modulating the innate immune response through VDR transcription.
TikBitten
p.s. BTW, today, 3/15/2011, is my three anniversary of being on the MP!!! I'm happy to report that significant progress has been made and would like to take a moment to express my deep gratitude to Dr. Marshall and all of the MP volunteers, past and present, for the time and effort they put forth so selflessly -- thank you all very much.
Last edited on Tue Mar 15th, 2011 19:59 by TikBitten
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Dx:Neurborreliosis 8/05|25D=46 1,25D=62 10/07|Avoid Sun&VitD since 10/07|Started Ph1&NoIRs 3/08|25D=18 3/08|25D=17 6/08|ModPh2 6/08|Ph2 9/08 stopped NoIRs|Ph3 1/09|25D=13 3/09|25D=10 5/09|25D=11 7/09|25D=15 9/09|25D=9 4/11
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Prof Trevor Marshall
Foundation Staff
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Posted: Tue Mar 15th, 2011 20:10 |
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Good to hear from you again And happy anniversary "Given the sensitivity with which metabolites, and their by-products, can so easily be detected now a days"
This is actually mistaken. It is very difficult to measure what is happening inside the phagocytic cells. With only a few exceptions (the video of HIV invasions, for example) all the current research is focused at much larger blobs of tissue. And much of it is performed in animals and cell lines, which are not the same as a living, breathing, human being...
As I sat and listened to the speakers at last week's NIH Human Microbiome conference, all bewailing the fact that their carefully done (expensive) experiments still had not produced firm hypotheses as to the cause of each disease, let alone confirm a cure, I couldn't help but feel a little warm about the success we achieved, and the way we achieved it - pure scientific understanding
We are keeping our eyes open for ways to definitively demonstrate the pathogenesis we have advanced, but no opportunities have arisen yet. Whenever I am contacted, it has always been by a scientist or physician who doesn't have a clue which foot to put in front of the other, and who hasn't even read our recent papers.
It is therefore not surprising that none of them have yet managed to knock down our hypothesis, which is, after all, the way that science is supposed to work...
ps: One of the microbiome studies showed that the ratio of microbial populations in the gut, an issue so exquisitely researched by Prof Jeff Gordon's group in mice, does not mirror the situation in humans. Obesity in humans is not related to gut microbial balance. You have no idea how sad that was making many of the delegates.. they have had to think it through again...
Last edited on Tue Mar 15th, 2011 20:14 by Prof Trevor Marshall
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TikBitten
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Posted: Tue Mar 15th, 2011 21:01 |
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Dr Trevor Marshall wrote: It is very difficult to measure what is happening inside the phagocytic cells. With only a few exceptions (the video of HIV invasions, for example) all the current research is focused at much larger blobs of tissue. And much of it is performed in animals and cell lines, which are not the same as a living, breathing, human being...
Very interesting response....
Little doubt you've thought long and hard on how to fully substantiate Olmesartan immune modulating properties. So I don't for a second question your response but, what came as surprise in your answer, however, is the manner by which you tied AMP production strictly to phagocytic cells.
My question, as previously posed, was formulated on my belief that the majority of human tissue expresses VDR and that Olmesartan not only up-regulates adaptive (Th2) immune response but innate (Th1) response as well. With the result being widespread increase in AMPs and, hence, potential plethora of readily detectable metabolites.
I have looked forward to the possibility that the West China study might reveal such a correlation. Am I wrong in all of my thinking here?
Quite concerned/TB
Last edited on Tue Mar 15th, 2011 21:04 by TikBitten
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Dx:Neurborreliosis 8/05|25D=46 1,25D=62 10/07|Avoid Sun&VitD since 10/07|Started Ph1&NoIRs 3/08|25D=18 3/08|25D=17 6/08|ModPh2 6/08|Ph2 9/08 stopped NoIRs|Ph3 1/09|25D=13 3/09|25D=10 5/09|25D=11 7/09|25D=15 9/09|25D=9 4/11
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