Optimum Pregnenolone Level?

[Phlogiston]

I'm hoping that some of you can give me some guidance on the optimum level of Pregnenolone for cognitive support and neuroprotection.

For several weeks I have been supplementing with LEF Pregnenolone, 100 mg daily on an empty stomach. I chose this rather high dose because other online sources said that pregnenolone is very poorly absorbed orally.

I just received my first test results -- I was told that my level was "less than 10". (I am unsure of the unit of measurement -- I will edit the post in a day or two when I receive the hardcopy results by mail.) However, my DHEA level had increased from the 220's to the 360's without any increase in DHEA supplementation.

The nurse practitioner I was speaking to was unable to give me any guidance about optimum pregnenolone levels, although she did say that in her experience people taking it for cognitive improvement usually took 100-200 mg. per day.

As I search online, I find much "pregnenolone is awesome" cheerleading from supplement manufacturers, but no guidance on optimum blood levels. This is in marked contrast to other frequently supplemented hormones like testosterone, DHEA, etc.

Has Dr. Bredesen defined an optimum range for neuroprotection?

[Julie G]

Phlogiston, I’ll share what I know in hopes that it may offer some help. My report indicated that my pregnenolone was “good” with a level of 94.0 ng/dL. Unfortunately, there was no reference range given although I suspect that it would change with gender, age, etc. My DHEA-s was also deemed “good” with a level at 170.1 ug/dL. Unfortunately, there was no reference range for me to interpret that one either.

I would first check to see if we are even comparing the same units of measurement. If so, SOMETHING seems to be preventing your cholesterol from converting to pregnenolone. What is your diet like? Are you currently on a statin? DHEA is downstream of pregnenalone, but that pathway seems to be working overly well . Was the doc who ordered the tests able to offer any insight?

[Jean]

Phlogiston, I found reference ranges for pregnenolone on my blood test reports from last year:
Premenopausal Females (18-51 years) 7-188 ng/dl
Postmenopausal Females (59-81 years 12-111 ng/dl

FYI Julies 94 ng/dL is good. It would be a nice place to land.

My recent pregnenolone blood test was below 10 too. I began taking pregnenolone recently, but could not tolerate even 50 mgs. I immediately got night sweats and acne. After researching, I decided to begin with a lower sublingual dose of 12 mg, then doubled to 25 mg. I can tolerate it now. I just had another blood test yesterday, so will see where I am. I do know that my thyroid is not working properly, so that may be part of the problem for me, since thyroid makes pregnenolone.

However, I have experienced good increases in the past when supplementing with pregnenolone. We don't know where you started, but since you were below 10, I would think 100 mgs would have raised your levels. Possible answers: You didn't take it long enough. You didn't absorb it?

Did you experience any good or bad effects from taking it?

[Phlogiston]

Jean, I haven't perceived any changes since I began supplementing with pregnenolone.

Julie, I don't know whether the increased DHEA levels come from the pregnenolone or if they result from changing my brand of DHEA supplement -- I switched from Vitamin Shoppe DHEA to LEF.

The nurse practitioner I spoke to about these results (who is in charge of my TRT, by the way) suggested that, since pregnenolone is essentially raw material for other hormones, looking at the downstream hormones might be a better indication as to whether my supp is being absorbed, rather than looking at pregnenolone results themselves. However, I don't think she is very well informed about pregnenolone supplementation.

The "unit of measurement" issue is really frustrating -- I'm supposed to have online access to my lab results, but I don't as of this morning. When I get the results in the mail I will confirm whether my level is actually deficient. I may just need to find a more effective way to supplement.

Jean, what type of sublingual pregnenolone have you been using? It sounds like it is extremely well absorbed.

[circular]

However, I don't think she is very well informed about pregnenolone supplementation.

My impression is that possibly no one is well informed about pregnenolone supplementation (?), in that there may not be very clear data behind it yet. Has anyone seen any good studies on it? I know Dr. Bredesen watches it and that it's thought to be neuroprotective. I was at about 15 and have only been taking 10 mg per day. Although Dr. Gundry says that amount won't do anything and he starts patients at 50 (I'm not sure under what circumstances), I have felt it helps (a little) with anxiety and feeling pleasure in life. (I'm petite so often react to small doses of things.) I upped to 20 temporarily and noticed these feelings were enhanced. I went back down to 10 because I'm not confident there's enough known about this or that low pregnenolone is the cause of my anxiety, and I read that once one is used to larger doses it can be hard to get off them. I would really like some good data-driven input on this.

Incidentally, when I started 10 mg of pregnenolone I also started 10 mg of DHEA. For me the DHEA caused acne and I stopped it. The pregnenolone didn't. Oddly, my testosterone went down using these and returned to normal after discontinuing the DHEA. Dr. Gundry said I would be the first female he's seen who's testosterone when down on DHEA and wondered if it was a goofy lab result.

I was also wondering how we know if low pregnenolone means we need to supplement it. Perhaps we're converting our stores efficiently. If our other hormones are normal, is low pregnenolone a problem? Do we take it for an independent neuroprotective effect? Is the science behind that strong?

If pregenenolone is neuroprotective, and cholesterol converts to pregenenolone, then is driving cholesterol down good for us? How much do we need in (non-oxidized) cholesterol stores to convert to sufficient pregnenolone naturally?

My endocrinologist said pregnenolone levels, as with many hormones, fluctuates a lot and one blood test isn't very indicative.

I haven't retested mine since supplementing yet.

[Julie G]

You ask some great questions, Circ. Dr. Brinton seems to be leading the field in making the connections between pregnenolone with AD. Here's an interesting piece summarizing her research: http://4abettermemory.com/memory/hormon ... in-health/

[Jean]

Very well stated Circ. I agree with every word and have like experiences. I am not amiable to taking huge amounts and not knowing where it is going in my body until I know for sure that it is nuero proctective. Currently, I can't tolerate DHEA or extra progesterone, so I am hoping small amounts of pregnenalone will go where it is needed. Its wait and see and then adjust if necessary. I am relieved to hear pregnenolone may not indicate the worst when the count is low, and think there may be validity in that if pregnenolone is the main precursor for other hormones, it may be deplete naturally.

Then there is all of our individual genetic hormone metabolism to consider.

Of course, I don't trust the hype of vitamin companies. There is more research out there that is more cautionary. Julie will read the link you just posted. Thanks.

[Jean]

Julie, this article http://www.lifeextension.com/magazine/2 ... olone/Page was a link presented in the link you posted. This information is the most informative, and for me - encouraging evidence regarding pregnenolone supplementation. Sorry, I did get carried away with quotes.

The first excerpt hits home since I am homogeneous for Gad1-high glutamine/low gaba.

Stimulation and Memory
Despite the apparent complexity of brain cells, or neurons, we can simplify matters considerably by thinking about their activities as either being stimulated or suppressed. Not surprisingly, most memory formation occurs as the result of stimulation of nerve cells. Stimulation generally results in the production of nerve branches known as dendrites, which connect to additional neurons, making the entire “switchboard” larger and more complex. These structures are formed by activating special “switches” in the brain. While there are a variety of such excitatory switches, the category called NMDA (N-methyl-D-aspartate) channels (or receptors) comprises the most important group. These channels must be activated for learning and memory to occur.

Now, here’s where it gets interesting! The typical excitatory brain chemical that activates those memory-enhancing NMDA receptors is the amino acid glutamate, which is present throughout the brain.15 And while glutamate is critical for normal learning, too much excitation by glutamate over time can damage neurons—in fact, overstimulation, or excitotoxicity, by glutamate is thought to be one of the underlying factors in neurodegenerative disorders such as Alzheimer’s disease.16,17 What makes pregnenolone so important in this context is that it seems to trigger the NMDA channels18,19 through a mechanism that is independent of glutamate,20 which in turn may account for the observed neuroprotective effects of pregnenolone on brain cells.21 The bottom line of all this intricate science is that pregnenolone may play a pivotal role both in laying down memories in the first place, and then preventing their loss by directly protecting the nerve networks that store them! These complementary and versatile actions of pregnenolone are sending shock waves of interest through the scientific community because of the enormous implications for treating all sorts of age-related disorders of memory.

Strong evidence from animal studies suggests that neurosteroid levels, including pregnenolone, diminish with advancing age.24 As pregnenolone is the parent compound of other vital neurosteroids such as dehydroepiandrosterone (DHEA),25 declining levels of pregnenolone could leave brain cells increasingly vulnerable to damage, such as overstimulation by neurotransmitters like glutamate.

As a result of normal aging, key hormone levels decline, resulting in a detrimental impact on memory and cognitive function. Scientists believe that the hormone pregnenolone has vast potential for maintaining healthy cognitive function and may be “the most potent memory enhancer yet reported.”1

Maintaining Healthy Pregnenolone Levels
Strong evidence from animal studies suggests that neurosteroid levels, including pregnenolone, diminish with advancing age. As pregnenolone is the parent compound of other vital neurosteroids such as dehydroepiandrosterone (DHEA),25 declining levels of pregnenolone could leave brain cells increasingly vulnerable to damage, such as overstimulation by neurotransmitters like glutamate.25,26

Evidence suggests that neuro-steroids such as pregnenolone may offer important neuroprotection in Alzheimer’s disease. When researchers introduced the destructive amyloid-beta protein into animal brains, the level of progesterone (a neurohormone synthesized from its direct precursor, pregnenolone) fell off dramatically. Likewise, in humans, Alzheimer’s disease patients have lower levels of pregnenolone, allopregnanolone (a pregnenolone metabolite) and DHEA-sulfate (DHEAS) in all the main memory-related areas of their brains, compared with control patients.30-32 Furthermore, the brains of patients with the highest neurosteroid levels display the lowest collections of the destructive amyloid-beta proteins.30

It therefore seems reasonable to speculate that as natural levels of pregnenolone and other neuro-steroids fall with aging and the onset of neurodegenerative diseases, supplementing with these vital compounds should have a neuroprotective effect. This is exactly what researchers have found. French scientists have paved the way in this field with their study of the effects of pregnenolone on cognitive aging. In fact, the results have been startling, with pregnenolone sulfate (the form found in brain tissue) completely reversing memory deficits in older, memory-impaired rats. 33

Scientists from the VA Medical Center in St. Louis explored pregnenolone’s benefits in memory retention using a conditioning task in animals that involved learning to avoid a mild electric shock to the foot.37,38 To their surprise, they discovered that pregnenolone displayed beneficial effects in improving memory retention at almost incredibly low doses.1 They also found the response to pregnenolone was much faster than expected had the supplement been working like a typical neurosteroid, leading to the conclusion that something much more dramatic was going on.

[Julie G]

Jean, glad you found some helpful information. G is always reminding us that LEF is out to sell supplements, but in this case I think your interest is warranted.

Below see a link to an earlier thread about pregnenolone/DHEA and more. Many of us got to hear Dr. Brinton speak about her research via an Us Against Alzheimer's teleconference: viewtopic.php?f=6&t=1140&p=11897#p11897

This is fascinating and could relate to E4 carriers in several ways. First, cholesterol homeostasis is disrupted in E4 carriers. As cholesterol is the precursor for pregnenolone and ALL hormones, this may be connected. Not surprisingly, hormones are also disrupted in AD patients. Dr. Brinton has taken this a step further for E4 women and has deeply delved into how menopause (loss of estrogen/downstream of pregnenolone) may hit us doubly hard as it exacerbates our already impaired cerebral glucose metabolism. We may have multiple opportunities for interventions...still unclear .

Perimenopause as a neurological transition state
http://www.nature.com/nrendo/journal/v1 ... 15.82.html

[Jean]

Thanks Julie. I just power read that entire link. It was very familiar due to my early experiences with biodentical hormone replacement (estrogen, progesterone, testosterone, along with compounded T4 and T3 and DHEA 15mg) right on or just before menopause.

Funny, I was told exactly the same thing as Circ about Pregnenolone, but began supplementing with it in 2006, which did triple my level at that time.

I just asked my doc whether he thought it would be safe for me to supplement my pregnenolone given it's very low status. He said he'd supplement with DHEA instead. He seemed to think there could be good reason to do that, with a relative absence of evidence supporting pregnenolone supplementation. He also emphasized how much all the hormones fluctuate during the day and between days, making one-shot tests generally not too helpful. But he did say it would be safe to use DHEA or pregnenolone, suggesting for a post-meno woman 10-25 of DHEA would be fine, and if adding pregnenolone he seemed to lean about the same amount.