Posted by Larry Hoover on July 3, 2004, at 11:38:19
In reply to Re: Pyroluria: Larry H., chemist, anyone...any help? » Larry Hoover, posted by Simus on June 21, 2004, at 16:22:19
> Thanks, Larry.
You're welcome. I'm sorry I dropped out of the discussion just when it was getting focussed. Real-life demands on my time, eh?
> > > After a lifetime of illness, both physical and mental, I did some on-line investigation and matched my ongoing symptoms to pyroluria.
> > I take it you're read descriptions along the line of this one?
> > http://drkaslow.com/html/pyroluria.html
> Yes, that was one of the sites I visited. But I kept migrating back to the work done by Dr. Pfeiffer and Dr. Walsh at the Pfeiffer Center. Have you heard of them or their work? It seemed to me to be credible.
Yes, it is, to a point. It seems to have stalled out twenty years ago, though. Nothing new. That concerns me. Second, I have had detailed interactions with people attending Pfeiffer, and I'm left with some serious concerns....lots of expensive tests, and lots of expensive supplements, less-than-ideal guidance (preprinted forms given by nurses, for example), and lack of efficacy over time.
> > > A positive test confirmed my suspicion.
> > Did you have a blood level of cis-linoleic acid done? And how is your glucose tolerance?
> My Fasting Plasma Glucose is 91 (<100 = normal). Is that what you meant by glucose tolerance?
Yes, along that line. That seems fine. Glucose tolerance is more specific, in that a fasting person is given a measured dose of glucose, and the insulin response and changes in blood glucose concentration in a set time, are measured.
> I haven't heard of a cis-linoleic acid test.
I was trying to understand what you meant by "a positive test confirmed my suspicion". I was wondering if you had actual fatty acid compositions tested.
> My total cholesterol is 149, LDL is 69, HDL is 38, and Triglycerides are 206. I know it isn't what you asked for, but it may or may not be of help to you to know that my cholesterol levels have been very low (perhaps too low ?)all my life.
Actually, long-term low cholesterol is its own risk factor. Cholesterol is the raw material for all the steroids, including e.g testosterone. Low cholesterol might be a unique trigger for depression.
> > > First of all, can someone tell me why the medical community generally seems to not be familiar with this condition?
> > I think it is seen as an idiopathic quirk, something unusual about a subject, but not pathological.
> Can you help me to understand what you mean by this, Larry?
When a doctor doesn't find a pathological mechanism (i.e. an accepted disease cause and effect relationship) to explain an unusual biochemical finding, they shrug and say "it's idiopathic", which just means you're unique. For example, having protein in the urine can be a finding related to kidney disease, or it can just be how that person normally is (idiopathic), and unrelated to disease.
> > > Second, I am having only moderate success treating it with supplements.
> > You have seen some improvement, then?
> Yes. Within 30 minutes of trying the B6 (50mg P5P/PAK) supplements, the "brain fog" immediately disappeared. But it did slowly return as the day wore on. Although the next doses helped, I didn't see as dramatic of an effect as with the first dose.
That's frequently how supplements seem to be. It doesn't change your need for the supplement. It is your perception that is changed.
> But then, I was in really bad shape mentally before the first dose. I have been constantly improving since. It has been slow, but then I am not the most patient person. The zinc supplements actually caused me to feel worse, but that was explained as the zinc was causing the excess copper in the organs to mobilize (apparently caused by years of zinc deficiency).
That's not how it works. Zinc in the gut reduces copper uptake from the gut. Zinc doesn't mobilize copper inside the body, as far as I have ever heard. Long-term zinc excess leads to copper deficiency (zinc is a treatment for Wilson's disease, which is excess tissue storage of copper). Zinc deficiency can lead to general increases in copper uptake (particularly where copper plumbing is common). It's an uptake regulation issue, not a biochemical one.
> I lowered the dose of zinc from 75mg to 25mg, and that helped considerably.
75 mg is above the recommended UL (Upper Limit) of zinc intake. 25 mg is fine.
> The tea I drink daily that contains ginseng, ginger, and green tea definitely helps. It helps calm anxiety symptoms and lifts mild depression.
You are getting psychoactive alkaloids, and high doses of phenolic antioxidants. No problems with any of that.
> > If you have defective d-6-d, you do not convert the dietary essential fatty acid cis-linoleic to the intermediate gamma-linolenic acid. All adverse health effects stem from this, directly. High urinary pyrroles infer high blood pyrroles.
> Are you saying that defective d-6-d can cause high blood pyrroles, or am I misunderstanding you?
That's exactly right.
> > Pyrroles bind to and inactivate B-6 and zinc, and pull them into the urine. So, you develop symptoms of malnutrition, despite an adequate diet, even with some supplements.
> > So, on the assumption that your body is pyrrolic due to GLA deficiency, the key thing is to dramatically increase your *daily* intake of GLA. EPO is one source, but on a gram-per-gram basis, borage oil has more GLA. It may take a long time for you to notice the benefits of supplementing GLA, because every cell membrane in your whole body will be competing for restoration of a normal fatty acid balance.
> > Every third or fourth day, take fish oil. Fish oil competes with GLA in some respects. That is both good and bad (I'll spare you the details), but taking GLA every day (e.g. 6-10 grams of borage oil), and 3-6 grams of fish oil every fourth day, balances out the effects. Take these oils with your fattiest meal of the day. If digestive upset occurs, cut the dose and increase as tolerance occurs. Your body will adapt.
> > Lar
> Wow. Thanks! I will assume you can tolerate a stupid question here.
The only definition of stupid question that I will accept is one that is not asked.
> Is fish oil CLA? If not, would taking CLA be harmful to me if I am deficient in GLA? I am not taking it - just curious.
This whole fatty acid thing is exceedingly complicated. I've had trouble learning some of it myself, and I'm a chemist.
CLA is conjugated linolenic acid. It is produced by microbial changes in the bond positions of linolenic acid during digestion, particularly in ruminant animals (e.g. cows).
Ordinarily, the double bond positions in linolenic acid are three carbons apart. Critters in cow stomachs have enzymes which bind to those double-bonded carbons, creating a reactive intermediate that sometimes "bounces off" the enzyme instead of being fully reacted. When the bonds get stable again, they sometimes move so they are only two carbons apart. Chemist geeks call that conjugation, when double bonds are two carbons apart. Anyway, the net effect is that butterfat, or more generally, milkfat, has CLA in it, as well as linolenic acid.
Synthetic CLA is produced by reacting linolenic acid with harsh chemicals. You get conjugated products that are different from the natural ones. As luck would have it, synthetic CLA is the one which is associated with health effects like fat loss.
CLA would not substantially interfere with the health effects of GLA or fish oil supplements, as far as I can tell.