![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 20 to 44 of 93. Go back in thread:
Posted by noa on April 5, 2003, at 10:08:41
In reply to Re: Larry Hoover Re: Ok- now who takes vitamins/, posted by Larry Hoover on April 3, 2003, at 18:42:34
I take folic acid, too, on the advice of my pdoc, for depression. The other supplement I take at his advice is chromium picolinate.
I take a multivitamin, as well. Not the Flintstones, though.
On last blood work, my folic acid and B12 levels were very high.
I also take Carlson's fish oil.
Posted by Larry Hoover on April 5, 2003, at 10:09:20
In reply to Larry Hoover Re: Ok- now who takes vitamins/, posted by McPac on April 5, 2003, at 0:34:00
> "Did your blood work include an assessment of homocysteine? (It's probably elevated.)"
>
> Yes! Before I began their treatment plan I had to go to a local lab in my town and have the homocysteine test.......a typical 30-second blood draw that cost $180!!A very expensive test. (I don't even know what the results were as I was going to wait until going back to Pfeiffer to ask, since they were sent the results).It is direct confirmatory evidence that your methylation biochemistry has been screwed up for an extended period of time.
> "I don't quite follow the need for supplemental methionine, as betaine will remethylate homocysteine to methionine, as will B-12".
>
> I don't know Larry. A lot of this stuff is very new to me.Can't hurt, I suppose. Probably unnecessary, IMHO.
> "I'd still take magnesium, too".
>
> I do! Pfeiffer also has me on calcium/magnesium, 1000mg/day of each. I like my magnesium...I think it relaxes me and helps me sleep more sound.My response, as well.
> "Response is said to take months, as you have to let your folate metabolism "wind down"."
>
> I know that Carl Pfeiffer wrote that high histamine reduction requires great patience and often takes 6-12 months to accomplish. I wondered why it would take so long (in contrast, many other nutritional treatments of Pfeiffer's, for other conditions that people have, produce dramatic results often in very short time periods). Is the long amount of time required for achieving the lowered histamine level mainly due to the lengthy folic acid metabolism process that you wrote about...or is it because of MANY various physiological factors that need corrected?Absolutely, it's many things. I keep coming to the conclusion that the histamine thingie is a marker of the general disturbance in biochemistry, rather than a causative factor, per se.
Your body has been burdened by a prolonged chronic stress reaction. It takes time for everything to come back into a healthier balance. I'm still bouncing back after *years* of nutritional supports.
Here's an automotive metaphor. Let's say you buy a brand new car, but you get totally caught up in the demands of work and family, and you forget to change the oil. Hell, you forget to even check it routinely. One day, the little red light comes on, you pull the dipstick, and there's none on the stick at all. Even though you rush off the get the oil changed, you now find that you are constantly having to check and top up the oil, just to keep it running. I think we're something like that. We're high maintenance.
> "I'm not sure that high histamine and blocked serotonin synthesis aren't both caused by something else".
>
> Very interesting Larry....re: serotonin, what things do you speculate (or know of) that may block it's production?There's a theoretical model proposed by Dr. Pall, one involving oxidative stress. You can get locked into a vicious biochemical circle which depletes B-vitamins and SAMe (among many other essential chemicals). Anything that depends on these depleted substances in turn gets depleted. The result is fatigue, depression, insomnia, cognitive problems.....
It just makes sense to me, fully explains all my symptoms, and has responded to the appropriate nutritional supports.
> "Zinc deficiency causes copper overload. I can't see how you can separate out the symptoms of one from the other (unless you have the genetic defect which leads to Wilson's disease)".
>
> I was reading a list of high copper toxicity symptoms on-line and the list of symptoms were dead-on to so many of mine (some symptoms which I had often wondered about for sooo many years and knew there must be a biochemical basis for; of course I STILL can't say for SURE but so many of my symptoms were there). I know that zinc-copper go together.
>
> "Zinc regulates copper, and blocks its uptake. So you really need zinc supplements. Also, selenium".
>
> Right again Lar! Pfeiffer has me taking zinc also! Soooooo funny that you mention selenium though....because that is one supplement that I myself have been wanting to add and now that you say that I am going to ask the Pfeiffer folks if I can add that!If you feel more comfortable asking, it's OK with me. ;-)
Selenium works with zinc in protecting against oxidative stress. Moreover, it directly blocks mercury toxicity (another possible burden).
> "Ask as many (questions) as you want to".
>
> I have one other question but I will need to gather a bit of info. before posing it correctly(re: sodium-potassium ratio).I'll be waiting.
> "I'm really interested in how well this works for you".
>
> Larry, you would sure make an awesome Pfeiffer employee! Every comment you made, every question you asked were all like it was coming from the Pfeiffer people. I have NO IDEA how you can understand, retain and explain the incredible mountain of information of biochemistry that you have. These fields (chemistry, biology, nutrition, physiology, etc.......all this info gives me a headache and I can't keep too much of it straight, lol. Take care and thanks!!!I did really well in school......
My *life* depends on my understanding these things. I'm not exaggerating. <shrug>
Lar
Posted by mopey on April 5, 2003, at 11:55:18
In reply to Re: Larry, I'm lost!, posted by Larry Hoover on April 5, 2003, at 9:53:22
Thanks, Larry, for your time, patience and expertise. I'll start on these and keep you posted.
> > Have been trying to keep up with all the info here, and so far have only figured out how much fish oil to take.
> >
> > Can you list what vitamins/supplements you'd recommend for someone with depression and anxiety to take?
> >
> > Thanks!
>
> I know you're looking for a simple answer, so I'll try to give one. You may want to think of my advice as a starting point. Later on, if certain symptoms persist, then more focussed supplementation trials would be worthwhile.
>
> B-vitamins: B-vitamins work together as a team, and you should take them together. There are a number of ways they're marketed, but you'll generally see them as B-complex, or B- followed by some number, like B-50. The number just gives the potency of each component, in either miligrams or micrograms, as appropriate. If you're just starting out, for one week, you can take three B-50s a day. The B's are water soluble, and any excess will simply spill into your urine, which will take on a yellow colour. But before your kidneys get at them, those B's are flooding your body with nutrients in your blood. From the blood, and only from the blood, can the different organ compartments of the body obtain their supplies. Your brain can't get any if your blood didn't have it first. So, ignore people who claim that you're just creating expensive urine. B's are cheap, and you've got to flood your body to replenish all your organs. After one week, you can cut back to 50-100/day.
>
> A good multi, like Centrum (or equivalent). Just because it's got a variety of nutrients.
>
> Minerals: You've seen lots of talk about magnesium. 2/3 of all people are chronically deficient in magnesium. Zinc and selenium are key components of many enzymes, and most people are deficient here, as well. Zinc 40 or 50 mg/day. Selenium, 200 micrograms/day. Chromium wouldn't hurt, either. 200-500 micrograms/day.
>
> Antioxidants: Vitamin C, 2,000 mg/day, in divided doses. This nutrient is far more important to mental health than most people realize. Alpha-lipoic acid, up to 200 mg/day.
>
> Methyl donors: Betaine (trimethylglycine or TMG), 500 mg/day, and/or B-12 1,000 mcg/day. (Betaine can be extremely activating, so you have to adjust the dose according to your individual response. 500 mg is just a suggestion.)
>
> You may wonder why I've listed B-12 separate from the other B's, but it is kind of unique. It contains a mineral ion (cobalt), unlike the other B's, and it is stored in the body (unlike any other B). I have come to believe that there is a sub-clinical B-12 deficiency syndrome, which is to say, one that has a number of symptoms but is not so well developed as to be identified as pernicious anemia. The RDA is something like 9 mcg, but you may not absorb it efficiently. B-12 is like magnesium in that a deficiency state in this nutrient will actually make it harder to absorb any from your food. By taking a large amount, some will diffuse across the gut membranes, even if the active transport mechanism isn't working.
>
> These are all relatively cheap. Walmart sells them all (there's no need to buy more expensive brand names, IMHO).
>
> Take with food, and let me know how things go.
>
> Lar
Posted by mopey on April 5, 2003, at 12:00:14
In reply to Re: Ok- now who takes vitamins/what kind(s)/how many?, posted by Larry Hoover on April 2, 2003, at 12:21:29
This sugar study is interesting. I always find I "need" a sugary treat when I'm feeling particularly depressed... wonder if it actually adds to the depression after an initial comfort benefit?
Will need to read more about this.
Thanks for the info.
Posted by Ron Hill on April 7, 2003, at 0:50:21
In reply to Re: Homocysteine, posted by Larry Hoover on April 4, 2003, at 18:55:51
Larry,
> > As I mentioned to you previously, about a year ago I had five months of good results using 200 mg/day of SAM-e to treat the atypical depressive phase of my BP II disorder. But then, rather suddenly, it started to make me VERY irritable (GRRRRRRRRRRRRRRRR!).
> The other possibility involves the whole concept of taking fully active exogenous substances, such as SAMe (or 5-HTP). In doing so, you bypass the normal regulatory processes which govern the concentration of these potent molecules. Perhaps, over five months, you gradually increased the concentration of one of the products of SAMe-dependent reactions because you kept taking it every day, and that product led to irritability. Your body will have a number of feedback inhibition signals which would have been activated by the increased product concentration; these would have been to no effect because the daily SAMe supply was independent of feedback control. My intuition lies with this latter explanation. Maybe you took too much/over too long a period of time.
Larry, would you expect that I would have the same problem if I were to take TMG instead of SAM-e?
Enough about me, lets talk about you for a minute. Is the Enada NADH providing any on-going benefit for you?
Okay, the minute’s up; back to my issues. What is your opinion of the information in one of the articles posted by JLx addressing the cortisol:DHEA hormonal ratio issue? More to the point, what is your position regarding DHEA supplementation as a method of balancing out elevated cortisol levels? For some time now, I have been interested in low dose DHEA supplementation. However, I’ve held off on conducting the trial because of what I have here-to-fore perceived to be risky manipulation of hormone levels. Here is the link to the article: http://www.drdebe.com/fitness.htm
-- Ron
Posted by Larry Hoover on April 7, 2003, at 9:39:59
In reply to Re: TMG » Larry Hoover, posted by Ron Hill on April 7, 2003, at 0:50:21
> Larry,
>
> > > As I mentioned to you previously, about a year ago I had five months of good results using 200 mg/day of SAM-e to treat the atypical depressive phase of my BP II disorder. But then, rather suddenly, it started to make me VERY irritable (GRRRRRRRRRRRRRRRR!).
>
> > The other possibility involves the whole concept of taking fully active exogenous substances, such as SAMe (or 5-HTP). In doing so, you bypass the normal regulatory processes which govern the concentration of these potent molecules. Perhaps, over five months, you gradually increased the concentration of one of the products of SAMe-dependent reactions because you kept taking it every day, and that product led to irritability. Your body will have a number of feedback inhibition signals which would have been activated by the increased product concentration; these would have been to no effect because the daily SAMe supply was independent of feedback control. My intuition lies with this latter explanation. Maybe you took too much/over too long a period of time.
>
> Larry, would you expect that I would have the same problem if I were to take TMG instead of SAM-e?No, I think not. We're deep into speculation, though.
> Enough about me, lets talk about you for a minute. Is the Enada NADH providing any on-going benefit for you?
I think it has. My pattern, established and reinforced over years now, has been that I slump after any prolonged exertion. I can't work a full-time job of any sort because of this. I've been lucky enough to find an employer who will take from me all that I can give them. In essence, I've been working one month on, one month off. The month off has been characterized by profound fatigue, cognitive and memory problems, irritabliity, mood decline. I'm usually already starting the slide before I even finish the month on, and the minimum takes a further two weeks to fully develop. I don't seem to be having this happen to me this time. I'm a little low, but it's not what I've come to expect.
I've been taking the NADH quite irregularly after that first week. It certainly had a cumulative effect, and I feared having taken too much. Anyway, I think it's helped. Too soon to be conclusive, but there's a positive trend.
> Okay, the minute’s up; back to my issues. What is your opinion of the information in one of the articles posted by JLx addressing the cortisol:DHEA hormonal ratio issue? More to the point, what is your position regarding DHEA supplementation as a method of balancing out elevated cortisol levels? For some time now, I have been interested in low dose DHEA supplementation. However, I’ve held off on conducting the trial because of what I have here-to-fore perceived to be risky manipulation of hormone levels. Here is the link to the article: http://www.drdebe.com/fitness.htm
>
> -- RonYa, I know. Hormones are potent. Hormones are tricky. Still, 50 mg of DHEA isn't going to do too much adverse, even if you didn't need it.
My intuition has led me to take "pulses" of some of the stimulating supplements. Little bursts of enhancement, rather than chronic supplementation. I feel more comfortable with one finger on the scale, rather than my fist.
Lar
Posted by Ron Hill on April 7, 2003, at 13:46:12
In reply to Re: TMG, posted by Larry Hoover on April 7, 2003, at 9:39:59
Hi Larry,
Thank you for your response.
> In essence, I've been working one month on, one month off.
Given your posting frequency lately, I assume you are currently off. When do you go back on?
> The month off has been characterized by profound fatigue, cognitive and memory problems, irritabliity, mood decline.
Have you ever had your cortisol levels measured?
As an aside, some of johnj's symptoms are somewhat similar to yours. Maybe there is a CFS component to John's dx (as you have alluded to in prior posts to John). In John's case, however, his "CFS-like" symptoms seem to be caused by the TCA he is taking.
> Ya, I know. Hormones are potent. Hormones are tricky. Still, 50 mg of DHEA isn't going to do too much adverse, even if you didn't need it.
YIKES! 50 mg?! I was thinking about 5 mg! In his book titled "Mind Boosters", Ray Sahelian, M.D. urges individuals to use the least amount possible and to take breaks from use. But Larry my real question for you was do you have an opinion regarding the idea that there may be some efficacy in using DHEA supplementation to bring cortisol in balance (as implied in the previously posted article)?
Thanks Larry!
-- Ron
Posted by Larry Hoover on April 7, 2003, at 15:04:21
In reply to Re: Cortisol and DHEA Balance » Larry Hoover, posted by Ron Hill on April 7, 2003, at 13:46:12
> Hi Larry,
>
> Thank you for your response.
>
> > In essence, I've been working one month on, one month off.
>
> Given your posting frequency lately, I assume you are currently off. When do you go back on?The end of this month. There's a very close match-up with the calendar.
> > The month off has been characterized by profound fatigue, cognitive and memory problems, irritabliity, mood decline.
>
> Have you ever had your cortisol levels measured?Yes, and DHEA, and DHEA/S. My blood had "normal" levels, but the question remains, what should be termed normal? If peoples' experience with thyroid hormone measurement is any indication, the normal range (an entire order of magnitude! for TSH) is not normal at all.
> As an aside, some of johnj's symptoms are somewhat similar to yours. Maybe there is a CFS component to John's dx (as you have alluded to in prior posts to John). In John's case, however, his "CFS-like" symptoms seem to be caused by the TCA he is taking.Well, I'd be concerned about the logical fallacy "post hoc, ergo propter hoc", i.e. after this, therefore because of this. Coincidence, in other words. You cannot exclude coincidental correlation by any logical means. The TCA could be a red herring.
> > Ya, I know. Hormones are potent. Hormones are tricky. Still, 50 mg of DHEA isn't going to do too much adverse, even if you didn't need it.
>
> YIKES! 50 mg?! I was thinking about 5 mg! In his book titled "Mind Boosters", Ray Sahelian, M.D. urges individuals to use the least amount possible and to take breaks from use. But Larry my real question for you was do you have an opinion regarding the idea that there may be some efficacy in using DHEA supplementation to bring cortisol in balance (as implied in the previously posted article)?
>
> Thanks Larry!
>
> -- RonI have trouble with mechanistic explanations. I'm more comfortable with empiricism. What do people feel like when they take DHEA? I don't need to know why. I'm interested in whether.
I've never seen DHEA in 5 mg doses, but that doesn't mean it isn't out there. DHEA supplementation studies have used up to 500 mg/day. The following studies used more than 50.
Surprisingly, I had trouble finding appropriate abstracts. Recently published studies had no abstract available.
Biol Psychiatry 1999 Jun 15;45(12):1533-41Comment in:
Biol Psychiatry. 1999 Jun 15;45(12):1531-2.
Dehydroepiandrosterone treatment of midlife dysthymia.Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR.
Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892-1276, USA.
BACKGROUND: This study evaluated the efficacy of the adrenal androgen, dehydroepiandrosterone, in the treatment of midlife-onset dysthymia. METHODS: A double-blind, randomized crossover treatment study was performed as follows: 3 weeks on 90 mg dehydroepiandrosterone, 3 weeks on 450 mg dehydroepiandrosterone, and 6 weeks on placebo. Outcome measures consisted of the following. Cross-sectional self-ratings included the Beck Depression Inventory, and visual analogue symptom scales. Cross-sectional objective ratings included the Hamilton Depression Rating Scale, the Cornell Dysthymia Scale and a cognitive test battery. Seventeen men and women aged 45 to 63 years with midlife-onset dysthymia participated in this study. Response to dehydroepiandrosterone or placebo was defined as a 50% reduction from baseline in either the Hamilton Depression Rating Scale or the Beck Depression Inventory. RESULTS: In 15 patients who completed the study, a robust effect of dehydroepiandrosterone on mood was observed compared with placebo. Sixty percent of the patients responded to dehydroepiandrosterone at the end of the 6-week treatment period compared with 20% on placebo. A significant response was seen after 3 weeks of treatment on 90 mg per day. The symptoms that improved most significantly were anhedonia, loss of energy, lack of motivation, emotional "numbness," sadness, inability to cope, and worry. Dehydroepiandrosterone showed no specific effects on cognitive function or sleep disturbance, although a type II error could not be ruled out. CONCLUSIONS: This pilot study suggests that dehydroepiandrosterone is an effective treatment for midlife-onset dysthymia.
Biol Psychiatry 1997 Feb 1;41(3):311-8
Dehydroepiandrosterone (DHEA) treatment of depression.Wolkowitz OM, Reus VI, Roberts E, Manfredi F, Chan T, Raum WJ, Ormiston S, Johnson R, Canick J, Brizendine L, Weingartner H.
Department of Psychiatry, University of California, San Francisco, School of Medicine 94143-0984, USA.
Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.
Am J Psychiatry 1999 Apr;156(4):646-9
Double-blind treatment of major depression with dehydroepiandrosterone.Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E.
Department of Psychiatry, University of California Medical Center, San Francisco, USA. owenw@itsa.ucsf.edu
OBJECTIVE: This study was designed to assess possible antidepressant effects of dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans. METHOD: Twenty-two patients with major depression, either medication-free or on stabilized antidepressant regimens, received either DHEA (maximum dose = 90 mg/day) or placebo for 6 weeks in a double-blind manner and were rated at baseline and at the end of the 6 weeks with the Hamilton Depression Rating Scale. Patients previously stabilized with antidepressants had the study medication added to that regimen; others received DHEA or placebo alone. RESULTS: DHEA was associated with a significantly greater decrease in Hamilton depression scale ratings than was placebo. Five of the 11 patients treated with DHEA, compared with none of the 11 given placebo, showed a 50% decrease or greater in depressive symptoms. CONCLUSIONS: These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression. Further, larger-scale trials are warranted.
Posted by johnj on April 7, 2003, at 15:17:49
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 7, 2003, at 15:04:21
Hi Larry,
Could you tell me what the S in DHEA/S is? I have never had my levels of cortisol tested and am thinking maybe this is a good idea along with my DHEA.
I am going to add some zinc to my cocktail and I also added alpha lipoic acid today too.
Still a little freaked by bursting with energy to none at all. The time change didn't help either. Thank you and have a good one.johnj
Posted by Larry Hoover on April 7, 2003, at 15:43:14
In reply to Re: Cortisol and DHEA Balance » Larry Hoover, posted by johnj on April 7, 2003, at 15:17:49
> Hi Larry,
>
> Could you tell me what the S in DHEA/S is?DHEA/S is the sulphate of DHEA. It's really not too important in the discussion so far, but it does tell you a little bit about how well your body is utilizing DHEA.
>I have never had my levels of cortisol tested and am thinking maybe this is a good idea along with my DHEA.
It can help you determine how well your adrenal glands are functioning.
> I am going to add some zinc to my cocktail and I also added alpha lipoic acid today too.
Selenium, too. Helps keep thyroid hormones happening.
> Still a little freaked by bursting with energy to none at all. The time change didn't help either. Thank you and have a good one.
>
> johnjHey John. One day at a time. For two years I've gone boom every other month, but I still can say that I'm growing more resilient over time. My first experience with over-exertion came after I fought with everything I had to meet a deadline for a report I was writing. I didn't make it. And, it took me eighteen months before I could do much of anything.
One theorist who advises CFS sufferers suggests that the rest must be proportional to the exertion (just as I've found in my own experience). Push for a week, rest for a week. Ya know? When you feel good, act. When you don't, rest.
Lar
Posted by jrbecker on April 7, 2003, at 16:09:26
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 7, 2003, at 15:43:14
Just to add further confusion to the debate, I have used both pregnenolone and DHEA as daily supplements for atypical symptoms. I find that pregnenolone is much more potent than DHEA at equal dosages. Not sure why, but perhaps it's because pregnenolone is not only used to manufacture DHEA but also produce cortisol. Since I'm an atypical case, I don't believe Preg has a damaging effect on my depression due to its cortisol connection. Both preg and DHEA have been tested for its AD effects and have been found to be moderately helpful. However, it seems the preference is towards DHEA in most of the literature, and seems like the safer bet. In terms of dosages, when I first started taking it, I saw great benefits from 50mg or more. But after a couple of weeks, it seems that the effects had built up in my system and I had to keep lowering my dose because of increased anxiety/agitation. Dr. Sahelian has written something to this build-up effect, saying that it takes a little time to see the full effectiveness of low dosages. Now, I only use 2 mg of pregnenolone 2-3 x per week. Part of the reason why such a low dose works is b/c of the build-up effect I mentioned, but also because I recently started up Remeron again. It's my belief that alpha-2 antagonism of the med is synergizing with the effect Pregnenolone, DHEA and its metablites have on alpha-2 receptors. So two mentions of warning: 1) if you're taking DHEA or Preg, beware of the build-up effect over the first few weeks. If you are experiencing any increased anxiety, agitation, or hostility, you should probably lower the dose. 2) If you are taking any med that has adrenergic effects, it will synergize with the effects of the DHEA or pregnenonolone -- (e.g. Serzone and Remeron... and this list might also flag SNRIs like Effexor, NARIs like Strattera, MAOIs, TCAs, and Stims)
Posted by Ron Hill on April 7, 2003, at 16:35:28
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 7, 2003, at 15:04:21
Larry,
> I have trouble with mechanistic explanations. I'm more comfortable with empiricism. What do people feel like when they take DHEA? I don't need to know why. I'm interested in whether.
Okay, then let me try it this way. Have you ever taken DHEA? If no, why not? If yes, how did it make you feel and why did you stop (I'm assuming you do not take it currently)?
> I've never seen DHEA in 5 mg doses, but that doesn't mean it isn't out there.Yeah, I bought a bottle of 5 mg DHEA tablets yesterday. I am a very med sensitive person.
> Surprisingly, I had trouble finding appropriate abstracts. Recently published studies had no abstract available.
Thank you very much for your time Larry. The abstracts were very interesting.
-- Ron
P.S. I promise not to bug you endlessly.
Posted by johnj on April 7, 2003, at 16:49:10
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 7, 2003, at 15:43:14
Thank you Larry,
Hindsight is always 20/20 and I see that now. I don't know much about CFS, but I should do some reading to see what pertains to me, if anything. Have any good suggestions.
I can see that my eating habits last week were very different than they had been when I was feeling good. Basically, eating out compared to preparing fresh veggies and stuff at home.
I can relate to pushing oneself past ones limit. The first time you just don't know where your limit is and it is a hard lesson finding it. I have decided that maybe I need some type of CBT, but when I felt great I didn't need anything like that.
A few years ago I tried selenium and something else and felt spacey in the afternoon. I will try it after I see what I currently take is working out.
I didn't get much sleep last night, but I was ok today, tired, but ok. Larry, is it ok to take the Mg alone? I was thinking of adding the zinc, C, E, and B at the same time. What do you think?
I talked to my brother on Saturday. He has PTSD from Vietnam, but is on no meds. He has done well, due mostly to working out. He is physically far superior to me, but we had a good talk and he accepts my depression/anxiety problem. At first he just couldn't get it and I was pretty down, but he has had a hard year and is finally getting it out so he is growing too.
I wish I had started supplemenation last year instead of going from 7.5 mg of tranzene to 22.5. I had previously been on 15, but went in half for over a year. When sleep was disrupted last year my pdoc just upped the benzo. I sometimes think it causes me some memory impairment. I hope for new discoveries and new meds with less side effects. Thanks Larry.
johnj
Posted by Ron Hill on April 7, 2003, at 16:59:52
In reply to Re: Cortisol and DHEA Balance, posted by jrbecker on April 7, 2003, at 16:09:26
JRBecker,
Thank you for sharing your experience with DHEA and preg.
> Just to add further confusion to the debate, I have used both pregnenolone and DHEA as daily supplements for atypical symptoms. I find that pregnenolone is much more potent than DHEA at equal dosages. Not sure why, but perhaps it's because pregnenolone is not only used to manufacture DHEA but also produce cortisol. Since I'm an atypical case, I don't believe Preg has a damaging effect on my depression due to its cortisol connection.
So is it your belief that atypical depression (i.e.; low motivation, anhedonia, anergy, hypersomnia, etc) is not correlated with elevated levels of cortisol?
-- Ron
Posted by Larry Hoover on April 7, 2003, at 19:21:50
In reply to Re: Cortisol and DHEA Balance » Larry Hoover, posted by Ron Hill on April 7, 2003, at 16:35:28
> Larry,
>
> > I have trouble with mechanistic explanations. I'm more comfortable with empiricism. What do people feel like when they take DHEA? I don't need to know why. I'm interested in whether.
>
> Okay, then let me try it this way. Have you ever taken DHEA? If no, why not? If yes, how did it make you feel and why did you stop (I'm assuming you do not take it currently)?Frankly, after looking at the subject anew, I don't know why I'm not taking any. I *have* used it before, but I don't really recall why I *don't* use it now. All I can come up with is a general resistance to mucking about with hormones. After refreshing my awareness about DHEA, I walked down the hall and swallowed 50 mg.
> > I've never seen DHEA in 5 mg doses, but that doesn't mean it isn't out there.
>
> Yeah, I bought a bottle of 5 mg DHEA tablets yesterday. I am a very med sensitive person.Me too. I never saw anything smaller than 25 when I last looked.
> > Surprisingly, I had trouble finding appropriate abstracts. Recently published studies had no abstract available.
>
> Thank you very much for your time Larry. The abstracts were very interesting.
>
> -- Ron
>
> P.S. I promise not to bug you endlessly.I promise not to be bugged....
Lar
Posted by Ron Hill on April 7, 2003, at 22:45:09
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 7, 2003, at 19:21:50
Larry,
> Frankly, after looking at the subject anew, I don't know why I'm not taking any. I *have* used it before, but I don't really recall why I *don't* use it now. All I can come up with is a general resistance to mucking about with hormones. After refreshing my awareness about DHEA, I walked down the hall and swallowed 50 mg.
Dude, you are way more impulsive than what I had you figured to be! It's kind of late in the day to be taking an activating substance like DHEA. I hope you can sleep okay tonight. If you get a chance tomorrow, let me know what it feels like in your brain.
> I promise not to be bugged....
I like your assertive attitude. Do what you gotta do to keep yourself healthy. If I can ever be of any help to you, be sure to let me know.
-- Ron
Posted by jrbecker on April 8, 2003, at 0:39:06
In reply to Re: Cortisol and DHEA Balance » jrbecker, posted by Ron Hill on April 7, 2003, at 16:59:52
> So is it your belief that atypical depression (i.e.; low motivation, anhedonia, anergy, hypersomnia, etc) is not correlated with elevated levels of cortisol?
>
> -- Ron
Ron,good question. It seems very likely based on the research that excessive cortisol plays a fairly direct role in causing the onset of depression. Although I think the issue is somewhat more complicated in atypical cases than in melancholic types. George Chrousos and Philip Gold of NIMH as well as Charles Nemeroff of Emory are some advocates for the role of the CRH pathway in terms of its more direct role [than monoamine metabolites] in the cause of depression.
A good read that might be a knowledgeable summary for those unfamiliar with this might be:
Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. PW Gold 1 and GP Chrousos 2. Molecular Psychiatry 2002, Volume 7, Number 3, Pages 254-275
To give a basic synopsis, it is hypothesized that in melancholic depression, the CRH pathway is being chronically stimulated, which simplifies to Corticotropin-releasing hormone --> ACTH --> Cortisol and NE release. This leads to the "typical" symptoms of depression due to chronic stress activation: low appetite, little sleep, anxiety, fearfulness of what the future holds, etc.In atypical depression, the stress system has pretty much fallen into disrepair. Whether it's because all atypicals were once melancholic in nature whose stress systems' have now crashed... well this is unknown. What is known is that atypical and melancholics have been found to be genetically distinct based on twin studies. Accordingly, many experts are beginning to think of the two types as completely different illnesses altogether. It's been shown that people with lower cortisol are more prone to PTSD, so perhaps there is a difference in predisposition that separates melancholics from atypicals as well.
Back to the stress system. It is believed that CRH is down-regulated in atypical sufferers (possibly due partly to feedback inhibtion from cortisol itself). Secondly, it is unclear whether cortisol itself is lower as well (there have been both studies that have measured high levels of cortisol as well as some that measured low levels of cortisol). Either way, it points to a problem of dysregulation of the stress system.
Another monkey wrench to throw into this theorizing is the idea of atypical depression as an offshoot of bipolar depression. There seems to be some good evidence of this when looking at the overlap of biplar II sufferers who have very comparable atypical features. If this is indedd the case, it might even suggest that atypical depression and that of bipolar illness have totally other mechanisms at fault besides the stress system.
In many ways, CRH and cortisol have been branded as conditionally "bad." However, this is in cases where it is being chronically overstimulated. CRH in the brain has been shown to be sort of like an endogenous cocaine. It increases dopamine and norepinpehrine release and has been related to all forms of primal drive and motivation. So, at normal levels it's a pretty good thing. Ron, this is where I actually answer your question specifically. Is excessive cortisol at fault for anhedonia? Yes seems to be the simple answer. Excessive cortisol is known to damage hippocampal regions of the brain as well as play a feedback stopgap to further CRH output. It is well known that this is what is occuring overtime in melancholic brains. Is this happening in atypical brains? My guess would be yes, but not to the same extent. Hippocampal damage(manifestation of atypical features) as well as low CRH (a major role in anhedonic symptoms) are major players in the illnesses' dabilitating effects. Whether anhedonic symptoms is due to ~current~ excessive cortisol is not clear. Unfortunately, a backwards way to correct this problem in atypical cases would be the introduction of a CRH potentiator to rejump the pathway. Who knows if this is the end-to-all-answers solution though.
What I do know is that stimulants, cocaine, exercise, selegiline, testosterone-replacement, and nicotine have all temporarily lifted my anhedonia. So obviously it's a Dopamine/NE connection, but it seems CRH is the more likely direct candidate at fault.
As for why I take the pregnenolone over the DHEA. I really can't say why. I don't know if in the end it's actually interefering somehow with my antidepressive treatment. But my belief is that it seems to have a more direct increase of dopamine through modulation of GABA than does DHEA. So maybe that's why I might be seeing more benefits in comparison to DHEA at equal doses. At the same time, it can also cause more anxiety. Either way, both supplements are somewhat similar in the end. As I mentioned before, the safer bet may be the DHEA.
JB
Posted by Larry Hoover on April 8, 2003, at 7:19:38
In reply to Re: Cortisol and DHEA Balance » Larry Hoover, posted by Ron Hill on April 7, 2003, at 22:45:09
> Larry,
>
> > Frankly, after looking at the subject anew, I don't know why I'm not taking any. I *have* used it before, but I don't really recall why I *don't* use it now. All I can come up with is a general resistance to mucking about with hormones. After refreshing my awareness about DHEA, I walked down the hall and swallowed 50 mg.
>
> Dude, you are way more impulsive than what I had you figured to be!Was that impulsive? Didn't feel like it from this end. I'd been mulling over using it for some time, I guess, and the research clinched it for me.
>It's kind of late in the day to be taking an activating substance like DHEA. I hope you can sleep okay tonight. If you get a chance tomorrow, let me know what it feels like in your brain.
I had a small difficulty going to sleep, but I had the same problem the night before, too (no DHEA), which I attributed to the time change.
> > I promise not to be bugged....
>
> I like your assertive attitude. Do what you gotta do to keep yourself healthy. If I can ever be of any help to you, be sure to let me know.
>
> -- RonDeal. <handshake>
L8r,
Lar
Posted by johnj on April 8, 2003, at 9:33:01
In reply to Re: Cortisol , posted by jrbecker on April 8, 2003, at 0:39:06
Great article, kind of hard since I am not versed in the technical terms. A few questions.
1) If the hippocamus is damaged, and I thought I read something about it regenerating cells every day, is repair with the right meds/supplements possible after a long term illness? I understand this is hard to answer, but what I can see in myself is a long term 6 month stressful event leading up to a crash about 1.5 years ago. I take lithium, a TCA, and a benzo, and all my pdoc did was increase my benzo when I had more anxiety and could not sleep. I guess I am looking at ways I can help reduce cortisol and/or stress effects. Or maybe I just need more rest since the period of high stress that I experienced. I had been pretty much symptom free for almost 8 years at that time.
What is out there that is close to a CRH or do most AD's act on cortisol is some way? Would it be advisable to see what my cortisol/DHEA levels are and if they are in the normal range? But, what is normal for me is the question too. I am med sensitive and the only herb/supplement I have tried that hasn't caused more anxiety is Mg. SAM-e made me more anxious. I was a biology major, but I can tell I need to bone up on things since I get lost rather quick in abstracts, recently concentration and motivation have been a big problem. Thank you
johnj
Posted by Ron Hill on April 8, 2003, at 9:53:39
In reply to Re: Cortisol , posted by jrbecker on April 8, 2003, at 0:39:06
JRB,
Thank you very much for taking the time necessary to type-up your detailed response. I need some time to chew on the information you have provided in your post and in the linked article. After I have it digested (to the extent allowed by my capabilities), I may need to get back to you with a follow-up.
Thank you friend.
-- Ron
-------------------------
> Ron,
>
> good question. It seems very likely based on the research that excessive cortisol plays a fairly direct role in causing the onset of depression. Although I think the issue is somewhat more complicated in atypical cases than in melancholic types. George Chrousos and Philip Gold of NIMH as well as Charles Nemeroff of Emory are some advocates for the role of the CRH pathway in terms of its more direct role [than monoamine metabolites] in the cause of depression.
>
> A good read that might be a knowledgeable summary for those unfamiliar with this might be:
>
> Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. PW Gold 1 and GP Chrousos 2. Molecular Psychiatry 2002, Volume 7, Number 3, Pages 254-275
>
> http://psyphz.psych.wisc.edu/front/740%20Class%20Spring%202003/Gold%20%20Organization%20of%20the%20stress%20system.pdf
>
>
> To give a basic synopsis, it is hypothesized that in melancholic depression, the CRH pathway is being chronically stimulated, which simplifies to Corticotropin-releasing hormone --> ACTH --> Cortisol and NE release. This leads to the "typical" symptoms of depression due to chronic stress activation: low appetite, little sleep, anxiety, fearfulness of what the future holds, etc.
>
> In atypical depression, the stress system has pretty much fallen into disrepair. Whether it's because all atypicals were once melancholic in nature whose stress systems' have now crashed... well this is unknown. What is known is that atypical and melancholics have been found to be genetically distinct based on twin studies. Accordingly, many experts are beginning to think of the two types as completely different illnesses altogether. It's been shown that people with lower cortisol are more prone to PTSD, so perhaps there is a difference in predisposition that separates melancholics from atypicals as well.
>
> Back to the stress system. It is believed that CRH is down-regulated in atypical sufferers (possibly due partly to feedback inhibtion from cortisol itself). Secondly, it is unclear whether cortisol itself is lower as well (there have been both studies that have measured high levels of cortisol as well as some that measured low levels of cortisol). Either way, it points to a problem of dysregulation of the stress system.
>
> Another monkey wrench to throw into this theorizing is the idea of atypical depression as an offshoot of bipolar depression. There seems to be some good evidence of this when looking at the overlap of biplar II sufferers who have very comparable atypical features. If this is indedd the case, it might even suggest that atypical depression and that of bipolar illness have totally other mechanisms at fault besides the stress system.
>
> In many ways, CRH and cortisol have been branded as conditionally "bad." However, this is in cases where it is being chronically overstimulated. CRH in the brain has been shown to be sort of like an endogenous cocaine. It increases dopamine and norepinpehrine release and has been related to all forms of primal drive and motivation. So, at normal levels it's a pretty good thing. Ron, this is where I actually answer your question specifically. Is excessive cortisol at fault for anhedonia? Yes seems to be the simple answer. Excessive cortisol is known to damage hippocampal regions of the brain as well as play a feedback stopgap to further CRH output. It is well known that this is what is occuring overtime in melancholic brains. Is this happening in atypical brains? My guess would be yes, but not to the same extent. Hippocampal damage(manifestation of atypical features) as well as low CRH (a major role in anhedonic symptoms) are major players in the illnesses' dabilitating effects. Whether anhedonic symptoms is due to ~current~ excessive cortisol is not clear. Unfortunately, a backwards way to correct this problem in atypical cases would be the introduction of a CRH potentiator to rejump the pathway. Who knows if this is the end-to-all-answers solution though.
>
> What I do know is that stimulants, cocaine, exercise, selegiline, testosterone-replacement, and nicotine have all temporarily lifted my anhedonia. So obviously it's a Dopamine/NE connection, but it seems CRH is the more likely direct candidate at fault.
>
> As for why I take the pregnenolone over the DHEA. I really can't say why. I don't know if in the end it's actually interefering somehow with my antidepressive treatment. But my belief is that it seems to have a more direct increase of dopamine through modulation of GABA than does DHEA. So maybe that's why I might be seeing more benefits in comparison to DHEA at equal doses. At the same time, it can also cause more anxiety. Either way, both supplements are somewhat similar in the end. As I mentioned before, the safer bet may be the DHEA.
>
> JB
>
>
>
Posted by Pfinstegg on April 8, 2003, at 9:54:35
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 8, 2003, at 7:19:38
Hi Larry... I think some people worry that if they take extra DHEA, they may raise their estrogen or testosterone levels over time, and be more at risk for breast or prostate cancer. (Relationship of serum dehydrepiantrosterone (DHEA) sufate, and 5-androstene, 3 beta, 17 beta-diol to risk of breast cancer in post-menopausal women, Cancer Epidemiol Biomarkers Prev 1997 Mar; 6(3):177-81) Although maybe somewhat less effective, 7-keto DHEA may help balance the DHEA-cortisol ratio, also, and it isn't supposed to be able to turn into either of those hormones in the body. (Preclinical Toxicology Evauation of 3-Acetyl-7-Oxo-Dehydoepiandrosterone, presented at Experimental Biology 98, April 19-22. San Francisco, CA by Humanetics Corp.)
But I must say that DHEA is interesting, with or without the 7-Keto. I found one study in which it was shown to prevent the uptake of cortisol into brain cells (Neurosteroid 7-hydroxylation products in the brain Int Rev Neurobiol 2001; 46:79-95), another which showed protection of the hippocampus from glutamate (Dehydroxyepiandrosterone protects Hippocampal Neurons against Excitatory Amino Acid-induced Neurtoxicity Proc Natl Acad Sci USA 1998 Feb 17;95(4):1852-7), and another which showed an increase in serum T3 without any change in TSH or T4 (A Randomized, DoubleBlind, Placebo-controlled Study of 3-acetyl-7-oxo-dehydroxyepiandrosterone in Healthy Overweight Adults, Humanetics Corp. The ones done by the Humanetics Corporation should of course be taken with a grain of salt, since they are the manufacturers. Still, that could be three neuroprotective actions!
I take the 7-Keto form about twice a week, but would really like to see more studies on its safety before I take it more frequently.
Pfinstegg
Posted by Ron Hill on April 8, 2003, at 10:00:02
In reply to Re: Cortisol and DHEA Balance, posted by Larry Hoover on April 8, 2003, at 7:19:38
Posted by Larry Hoover on April 8, 2003, at 11:09:18
In reply to Pls tell me what the DHEA feels like in your brain (nm) » Larry Hoover, posted by Ron Hill on April 8, 2003, at 10:00:02
Posted by Larry Hoover on April 8, 2003, at 11:59:30
In reply to Re: Cortisol , posted by jrbecker on April 8, 2003, at 0:39:06
> A good read that might be a knowledgeable summary for those unfamiliar with this might be:
>
> Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. PW Gold 1 and GP Chrousos 2. Molecular Psychiatry 2002, Volume 7, Number 3, Pages 254-275
>
> http://psyphz.psych.wisc.edu/front/740%20Class%20Spring%202003/Gold%20%20Organization%20of%20the%20stress%20system.pdfI can't think of a recent occasion when I have so thoroughly read any paper as I have studied this one. Thank you very much for the link.
Of course, the obvious questions arising from this study amount to :"So what can we do about that?"
What strikes me are the similarities to the theories presented many years ago by Hans Selye. For an exceedingly brief explanation, go to:
http://www.healthnewsnet.com/gap.htmlNow, back in the '20s and '30s, when Selye first defined his concepts of stress reactions, there was no way to directly measure the biochemical characteristics of these states. Still, I see the echoes in the current paper. There have been a number of nutritional and herbal "treatments" suggested for the exhaustion phase of chronic stress, based primarily on "softer" science than that presented here, but probably finding increasing validity over years of refinement. It shouldn't take too much trouble to find those ideas.
There is another aspect to the effect of prolonged stress, one that is not even tangentially mentioned in the comprehensive review referenced above: oxidative stress. Dr. Pall has some compelling evidence for the cyclic "locking in" of pathological levels of peroxynitrite as a mediator of the debilitating effects of chronic fatigue, PTSD, and fibromyalgia. It's not a stretch to apply chronic oxidative stress to atypical depression.
Much to think about here. And well worth a re-read.
Lar
Posted by Ron Hill on April 8, 2003, at 12:07:50
In reply to Re: DHEA feels like clarity (nm) » Ron Hill, posted by Larry Hoover on April 8, 2003, at 11:09:18
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