haidut

Member
Joined
Mar 18, 2013
Messages
17,435
Location
USA / Europe
About a month ago, I made a post in regards to aspirin becoming a new treatment for osteoporosis. Several months ago, I made another post about an in-vitro study demonstrating powerful anabolic effects of pregnenolone (P5) on bones. Apparently, the protective effects of P5 on bone health are known in certain circles and there have been attempts to synthesize synthetic P5 derivatives to use as anti-osteoporosis agents, despite the fact that plain P5 works quite well. Now, a new study has been published, which successfully demonstrated the bone-anabolic effects of P5 in-vivo, and at physiological doses too. Perhaps the most important result is that P5 managed to prevent/reverse osteoporosis driven by BOTH chronic inflammation driven by endotoxin/LPS and menopause (ovariectomy model). The mechanism of action of P5 was through dampening of inflammation driven by endotoxin/LPS, and prevention of osteoclast formation (and thus bone resorption). The effective HED used in the study was about 0.8 mg/kg daily and duration of treatment was 4 weeks, but the administration was every other day instead of daily. That means on a daily basis one could take half the dose (0.4 mg/kg) or maybe use the once weekly dose the size of an aspirin tablet as Peat mentioned in one of his articles. Those are perfectly physiological doses as most young, healthy people produce up to 50mg daily. Also, the 4-week treatment was only needed for the menopause-driven osteoporosis. The protective effects of P5 on endotoxin/LPS induced bone loss were visible after only 7 days of treatment. Finally, a lower dose (HED of 0.08 mg/kg every other day) did not have protective effects in the menopause model but still had strong protective effects in the endotoxin/LPS model.
As an interesting side note, the study below raises serious doubts about estrogen as a protective factor for bones and its role in menopause-driven osteoporosis. P5 is known to have NO effect on estrogen levels in rodents, and in fact it has been known to act as an estrogen antagonist, partially through its conversion to progesterone.

Pregnenolone Inhibits Osteoclast Differentiation and Protects Against Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Indu... - PubMed - NCBI
"...On the other hand, Preg treatment (both low and high doses) significantly lessened the destructive effects of LPS, reducing inflammatory cell infiltration and osteoclast activity. In particular, treatment with high dose Preg (10 mg/kg bodyweight) almost completely prevented LPS-induced bone destruction and bone loss, with bone volume almost comparable to that of sham controls (Figures 6A, C). The number of TRAP+ve osteoclasts in high dose Preg treated group were also comparable to sham controls indicating the inhibition of osteoclast formation and therefore activity (Figure 6E)."

"...Apart from the local suppressive effect of Preg on osteolysis, we further investigated whether Preg can be systemically used to prevent bone loss. Similar protective effects were seen in the OVX-induced bone loss model but only when mice were given high-dose of Preg (10 mg/kg bodyweight). No significant protective effects were observed when mice were given low dose of Preg (1 mg/kg bodyweight) over the 4 week experimental period (Figure 8). Three-dimensional reconstructions of the tibial bone tissue shows significant reduction in bone volume and trabecular bone loss after bilateral ovariectomy (Figures 8A, B). TRAP staining of the tibial bone sections shows significant enhancement in the total number of TRAP+ve osteoclasts and the number of osteoclasts lining the trabecular bone surface (Figures 8C–E). However, treatment with low dose Preg did not protect against OVX-induced bone loss and trabecular bone deterioration. Only at high doses of 10 mg/kg did Preg demonstrate its protective effect against OVX-induced reduction in trabecular bone via the suppression of osteoclast formation and activity. In addition, there was no significant difference in cortical bone thickness between OVX and Preg treatment groups. (Figure 8B). Thus collectively, and in general, Preg particular at high doses demonstrates protective against inflammatory bone destruction as well as postmenopausal bone loss via the inhibition of osteoclast formation and bone resorption. It is worth noting that no adverse effects were observed in mice treated with high dose Preg suggesting that Preg may exhibit a relatively safe in vivo drug profile."

"...the level of Preg dramatically decline with age, with the levels at the age of 75 being 60% less than the levels produced in the mid 30s (Roberts, 1995; Morley et al., 1997). It has been proposed that Preg has potential as a novel anti-osteoporotic agent (Maurya et al., 2017). In our study we provided further evidence to support this claim. Preg was found to protect mice against both LPS-induced inflammatory bone destruction as well as OVX-induced bone loss in vivo via the inhibition of osteoclast formation and bone resorptive activity. In vitro cellular assays further confirmed a direct inhibitory effect of Preg on RANKL-induced osteoclast formation from primary BMMs and also mature BMM-derived osteoclast bone resorption. Our study did not find any effect of Preg on the osteogenic differentiation of BMSCs or downstream mineralization activity."

"... In previous studies, it has been confirmed that Preg can promote the production of ROS (Li et al., 2017). However, in our studies, we showed that Preg treatment significantly reduced intracellular ROS levels during RANKL-induced osteoclast formation. To our knowledge, our study is the first to show that Preg exhibits potent anti-oxidant properties, and the effect of Preg on RANKL signaling cascade may involve the suppression of ROS induction."

"...In all, our current study provides some interesting finding for the biological effects of Preg on osteoclast formation and activity. Preg was found to inhibit RANKL-induced differentiation of primary BMMs into multinucleated osteoclasts and subsequent downstream bone resorptive activity in vitro and prevented osteoclast-mediated inflammatory bone destruction and estrogen-deficiency induced bone loss in vivo. The anti-osteoclastogenic effect of Preg could be in part attributed to the suppression of RANKL-induced ROS generation and activation of ERK and NF-κB. This consequently attenuated the induction of c-Fos and NFATc1, key transcription factors for osteoclast formation and function. These results provide some promising evidence for the use of Preg in the prevention or therapeutic treatment of osteoclast-mediated osteolytic bone diseases."
 
Similar threads
Thread starter Title Forum Replies Date
E Can Pregnenolone replace Progesterone temporarily during Pregnancy? Female Issues 1
O Pregnenolone Powder Won't Dissolve in DMSO Supplements, Pharmaceutical Drugs 0
V Pregnenolone, Progesterone, DHEA supplementation advice Supplements, Pharmaceutical Drugs 7
F Pregnenolone & or DHEA on TRT for anxiety&hair loss Ask For Help or Advice 4
M Pregnenolone supplementation causing hairloss Pregnenolone 10
ddjd progesterone causing headaches + poor sleep. pregnenolone completely relieves symptoms Ask For Help or Advice 11
Epistrophy Pregnenolone + Testosterone Base = All natural pain killer Experiments 24
Yon Your experience with progesterone, T3/T4 and pregnenolone Health 14
deliciousfruit Pregnenolone makes me suicidal Ask For Help or Advice 19
pauljacob Pregnenolone Gave Me Vertigo Pregnenolone 10
deliciousfruit Is pregnenolone safe for adolescents? Supplements, Pharmaceutical Drugs 4
haidut Oral pregnenolone as hormone replacement therapy (HRT) in humans Scientific Studies 16
ddjd ways to increase CYP11A activity other than K2MK4? Cholesterol→Pregnenolone Ask For Help or Advice 10
O Those Who Tried Oral Pregnenolone: Did You Notice A Facelift Effect? Polls 6
pauljacob Can I Break Open A Niacinamide, Pregnenolone Capsule? Supplements, Pharmaceutical Drugs 4
cjmorin Pregnenolone Hair Fall? Hair & Nails 16
cjmorin Pregnenolone Hair Fall? Hair & Nails 0
K I Took 100mg Pregnenolone ED For Years - Please Help Me Supplements, Pharmaceutical Drugs 63
E Pregnenolone Solo Ask For Help or Advice 5
B Central Serous Retinopathy / (Piracetam/Pregnenolone/TRT/Cortison) Health 21
R Pregnenolone Improving Posture/muscle Tightness? Supplements 11
J Male 25 / Pregnenolone 50mg - Hot Flashes - Raising Metabolism? Supplements, Pharmaceutical Drugs 2
E Philosopher AI About Pregnenolone Pregnenolone 11
E If Anyone Is Interested I'll Be Sharing COA Of Douglas Labs Pregnenolone Pharmaceutical Drugs 2
haidut Pregnenolone (P5) May Be Ergogenic And Helps Recovery From Exercise Scientific Studies 0
ScurveDream DHEA Or Pregnenolone To Combat Possible Caffeine-induced Stress? Ask For Help or Advice 8
Cecilia L. High Pregnenolone, High Progesterone, High Estradiol, Low D Female Issues 13
C Can Pregnenolone Make Fatigue Worse? Ask For Help or Advice 8
C Are Pregnenolone Capsules Safe To Take Every Day? Ask For Help or Advice 10
noqcks Eczema Cleared Up With Pregnenolone? Skin 12
D Why Does Low Dose Pregnenolone Affect Me So Powerfully? Pregnenolone 15
Light Micronized Pregnenolone Is Dissolving Well In Shea Butter Pregnenolone 3
F Pregnenolone Makes Me Freezing Cold? Pregnenolone 1
haidut Pregnenolone Safe And Effective In Big Human Trial For Back Pain Scientific Studies 0
B Pregnenolone Supplementation Supplements, Pharmaceutical Drugs 0
B Impact From 25mg Pregnenolone Oral Daily On Progesterone And DHT Levels? Hormones 1
cyclops Why Does Ray Think Its Ok To Take Extremely Large Doses Of Pregnenolone? Pregnenolone 25
Moshi Pregnenolone And The GABA Paradox Thyroid and Hormones 15
S Pregnenolone And Androsterone Together? Supplements, Pharmaceutical Drugs 27
M Pregnenolone And Body Temp Supplements, Pharmaceutical Drugs 17
Peatogenic Can Pregnenolone Supplementation Raise Cortisol? Pregnenolone 7
fever257 First Time On Pregnenolone. All I Can Say Is Wow Ask For Help or Advice 10
haidut Pregnenolone (P5) Fully Prevents Testicular Atrophy Due To Steroid (ab)use Or High Estrogen Scientific Studies 55
B Pregnenolone + DHEA: Daily Or Weekly? Ask For Help or Advice 17
I Magnesium + Pregnenolone Insomnia, Sleep Issues 3
Lenny How Does One Use Pregnenolone/DHEA Powder? Supplements, Pharmaceutical Drugs 3
R Pregnenolone In Canada Ask For Help or Advice 2
J What Brand Of Pregnenolone Is Best To Take? Cortisol, Serotonin, Histamine 8
Lokzo PREGNENOLONE: What's Your Experience? Experiments 3
P Massive Pregnenolone Increase From THC! Scientific Studies 9

Similar threads

Top