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haidut

Member
Joined
Mar 18, 2013
Messages
18,214
Location
USA / Europe
I have always been suspicious of PPI drugs. There are many reasons for it, including the falsified clinical trial data to conceal increased risk of gastric cancer, the idiotic premise that gastric acid increases with age, the kidney failure side effects, and the calcium/magnesium depletion being the among the main. I have a few colleagues who are all on PPI drugs and they have all started to look rather feminine. In addition, a few of them developed gyno and all of them have pretty bad mood swings, poor libido, with one developing severe depression. The official explanation is that it is probably due to the magnesium deficiency which PPI drugs are known to cause. But that is usually not enough to cause feminization, gyno or poor libido. So, while researching the effects of various steroid inhibitors I came upon this gem. As you can see, PPI drugs inhibit steroidogenesis from cholesterol at the very top - i.e. the side cleavage enzyme that converts cholesterol into pregnenolone inside the mitochondria. About as nasty as it gets.


In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis. - PubMed - NCBI
"...The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole. Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 beta hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and alpha cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 alpha hydroxycholesterol was inhibited by 83% in the presence of 100 micrograms omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 alpha hydroxylated derivatives was inhibited by 20-40% whereas cortisol production from added 11 deoxycortisol was not affected. These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 beta hydroxysteroid dehydrogenase, 17 alpha hydroxylase or 11 beta hydroxylation; 21 hydroxylase activity may be marginally attenuated."
 

aguilaroja

Member
Joined
Jul 24, 2013
Messages
836
...As you can see, PPI drugs inhibit steroidogenesis from cholesterol at the very top - i.e. the side cleavage enzyme that converts cholesterol into pregnenolone inside the mitochondria.

Good one. Haidut has other posts describing problems with the PPI’s. It’s a long list. Certainly, the steroid suppression effect may be a big part of these problems.

There were reports of problems with PPI’s from the beginning of their use, that got squashed by the bulldozer of a new, profitable drug. It is good to recall that the PPI’s replaced fairly effective (in medical-industrial terms) H2 blockers [see haidut’s posts on famotidine]. And both, in turn, replaced the much safer antacids [calcium carbonate or magnesium carbonate, anyone?] which also worked but needed to be used more frequently.

haidut posted earlier on the association between PPI’s and dementia:
Anti-acid Drugs (ppi) May Cause Dementia

Research describes impaired thinking from PPI use, dementia or not:
Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software. - PubMed - NCBI
“Studies have shown that proton pump inhibitors (PPIs) increase the brain burden of amyloid-beta (Aβ) and also create vitamin B12 deficiency. However, these two phenomena have deleterious effect on cognition and Alzheimer's disease (AD).…
“We found statistically and clinically significant impairment in visual memory, attention, executive function, and working and planning function.”

PPI’s are associated with lower magnesium:
Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study. - PubMed - NCBI
“PPI use is associated with hypomagnesemia in the general population.”

PPI’s may be associate with muscle pain (myalgia, myopathy):
Proton Pump Inhibitors: Risk for Myopathy? - PubMed - NCBI
“A limited body of published data suggests that PPI use has been associated with myopathy-like symptoms without long-term effects following discontinuation. Although myopathy is a rare adverse effect observed with PPIs, it can be a serious side effect to be considered when starting a patient on acid suppression therapy.”

PPI’s are associated with greater risk of headache:
Proton pump inhibitor-related headaches: a nationwide population-based case-crossover study in Taiwan. - PubMed - NCBI
"PPI usage is associated with an increased risk for acute headache. Female patients and use of lansoprazole or esomeprazole present the greatest risks of headache."

The evidence continues to accumulate that PPI’s may increase fracture risk and osteoporosis:
The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: A prospective c... - PubMed - NCBI
“…osteoporosis and fracture risks were increased in this cohort of elderly females subsequent to PPI prescription.”
Use of proton pump inhibitors is associated with fractures in young adults: a population-based study. - PubMed - NCBI
“PPI use was associated with fracture in young adults…. adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.”
Use of proton pump inhibitors is associated with lower trabecular bone density in older individuals. - PubMed - NCBI
“PPI use might increase the risk of fractures in older subjects through its detrimental effects on trabecular bone. “

And older patients sent home from hospital on high dose PPI’s were more likely to die within one year:
Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. - PubMed - NCBI
“In older patients discharged from acute care hospitals, the use of high-dose PPIs is associated with increased 1-year mortality. Randomized controlled studies including older frail patients are needed.”

I am not a public health expert, but I am guessing accelerated mortality can be classified as a major side effect.
 

forterpride

Member
Joined
Jun 7, 2013
Messages
239
I have always been suspicious of PPI drugs. There are many reasons for it, including the falsified clinical trial data to conceal increased risk of gastric cancer, the idiotic premise that gastric acid increases with age, the kidney failure side effects, and the calcium/magnesium depletion being the among the main. I have a few colleagues who are all on PPI drugs and they have all started to look rather feminine. In addition, a few of them developed gyno and all of them have pretty bad mood swings, poor libido, with one developing severe depression. The official explanation is that it is probably due to the magnesium deficiency which PPI drugs are known to cause. But that is usually not enough to cause feminization, gyno or poor libido. So, while researching the effects of various steroid inhibitors I came upon this gem. As you can see, PPI drugs inhibit steroidogenesis from cholesterol at the very top - i.e. the side cleavage enzyme that converts cholesterol into pregnenolone inside the mitochondria. About as nasty as it gets.


In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis. - PubMed - NCBI
"...The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole. Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 beta hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and alpha cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 alpha hydroxycholesterol was inhibited by 83% in the presence of 100 micrograms omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 alpha hydroxylated derivatives was inhibited by 20-40% whereas cortisol production from added 11 deoxycortisol was not affected. These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 beta hydroxysteroid dehydrogenase, 17 alpha hydroxylase or 11 beta hydroxylation; 21 hydroxylase activity may be marginally attenuated."

so what's the alternative? I've have horrible acid reflux and nothing else works! It's incredibly disheartening.
 
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