15 replies to this topic

[CobaltThoriumG]

Thread title meant to read "Bilirubin as potent antioxidant and idea concerning its relation to fasting."

Bilirubin recently has become a point of interest for me after repeated blood tests showed my bilirubin to be 2 to 2.5 times high normal. I thought I might have mono because mono can cause elevated bilirubin, I felt fatigued, and an EBV test suggested a recent infection. But my doctor diagnosed me with Gilbert's Syndrome, a fairly common genetic unconjugated hyperbilirubinemia that affects somewhere between 5 and 10% of the population. I plan to have my bilirubin tested again in six months or so. If it is still elevated, I may confirm the diagnosis through a genetic test that the University of Chicago offers (link). Here's a little more on the genetic basis for Gilbert's.

Until relatively recently bilirubin was viewed as a toxin. However, it is now seen as a potent antioxidant (link), even more potent than glutathione. From the last link:

"While it takes one glutathione molecule to consume an oxidant, a single bilirubin molecule can take care of 10,000 oxidant molecules, the scientists found."

So perhaps Gilbert's Syndrome is a desirable mutation and should be among genes considered longevity genes. There are studies that show a correlation between Gilbert's Syndrome and lower incidence of certain diseases such as arteriosclerosis and cancer (link).

Here's an interesting patent that discusses bilirubin and reduced all-cause mortality observed in men with Gilbert's Syndrome.

Interestingly, fasting can cause hyperbilirubinemia (link). I wonder whether this may be one of the reasons that fasting has demonstrated health benefits.

Does this interest anyone?

Edited by CobaltThoriumG, 21 September 2008 - 10:12 PM.

[brotherx]

Absolutely! :-)
I have elevated Bilirubin levels myself - but never felt any negative side effect from it!
Thanks for the links - I will have a look!

Cheers

Alex

<p>Thread title meant to read "Bilirubin as potent antioxidant and idea concerning its relation to fasting." </p>

Bilirubin recently has become a point of interest for me after repeated blood tests showed my bilirubin to be 2 to 2.5 times high normal. I thought I might have mono because mono can cause elevated bilirubin, I felt fatigued, and an EBV test suggested a recent infection. But my doctor diagnosed me with Gilbert's Syndrome, a fairly common genetic unconjugated hyperbilirubinemia that affects somewhere between 5 and 10% of the population. I plan to have my bilirubin tested again in six months or so. If it is still elevated, I may confirm the diagnosis through a genetic test that the University of Chicago offers <a href= "http://genes.uchicag...bert.pdf">(link)</a>. Here's a little more on the genetic basis for Gilbert's.

Until relatively recently bilirubin was viewed as a toxin. However, it is now seen as a potent antioxidant (link), even more potent than glutathione. From the last link:

"While it takes one glutathione molecule to consume an oxidant, a single bilirubin molecule can take care of 10,000 oxidant molecules, the scientists found."

So perhaps Gilbert's Syndrome is a desirable mutation and should be among genes considered longevity genes. There are studies that show a correlation between Gilbert's Syndrome and lower incidence of certain diseases such as arteriosclerosis and cancer (link).

Here's an interesting patent that discusses bilirubin and reduced all-cause mortality observed in men with Gilbert's Syndrome.

Interestingly, fasting can cause hyperbilirubinemia (link). I wonder whether this may be one of the reasons that fasting has demonstrated health benefits.

Does this interest anyone?

[brotherx]

This is a 'nice' conclusion of one of the studies you've linked: :-)

"In summary, based on available data and in accord with the analysis by Sedlak and Snyder,1 it may be postulated that serum bilirubin is a major clinically relevant cytoprotectant, contributing substantially to protection against oxidative stress. However, additional studies are necessary to uncover all the pathophysiologic associations and mechanisms involved."
Source:http://pediatrics.aappublications.org/cgi/content/full/115/5/1411

Cheers

Alex

<p>Thread title meant to read "Bilirubin as potent antioxidant and idea concerning its relation to fasting." </p>

Bilirubin recently has become a point of interest for me after repeated blood tests showed my bilirubin to be 2 to 2.5 times high normal. I thought I might have mono because mono can cause elevated bilirubin, I felt fatigued, and an EBV test suggested a recent infection. But my doctor diagnosed me with Gilbert's Syndrome, a fairly common genetic unconjugated hyperbilirubinemia that affects somewhere between 5 and 10% of the population. I plan to have my bilirubin tested again in six months or so. If it is still elevated, I may confirm the diagnosis through a genetic test that the University of Chicago offers <a href= "http://genes.uchicag...bert.pdf">(link)</a>. Here's a little more on the genetic basis for Gilbert's.

Until relatively recently bilirubin was viewed as a toxin. However, it is now seen as a potent antioxidant (link), even more potent than glutathione. From the last link:

"While it takes one glutathione molecule to consume an oxidant, a single bilirubin molecule can take care of 10,000 oxidant molecules, the scientists found."

So perhaps Gilbert's Syndrome is a desirable mutation and should be among genes considered longevity genes. There are studies that show a correlation between Gilbert's Syndrome and lower incidence of certain diseases such as arteriosclerosis and cancer (link).

Here's an interesting patent that discusses bilirubin and reduced all-cause mortality observed in men with Gilbert's Syndrome.

Interestingly, fasting can cause hyperbilirubinemia (link). I wonder whether this may be one of the reasons that fasting has demonstrated health benefits.

Does this interest anyone?

[brotherx]

By the way - you may find this link usefull: http://www.gilbertssyndrome.com/

Cheers

Alex

<p>Thread title meant to read "Bilirubin as potent antioxidant and idea concerning its relation to fasting." </p>

Bilirubin recently has become a point of interest for me after repeated blood tests showed my bilirubin to be 2 to 2.5 times high normal. I thought I might have mono because mono can cause elevated bilirubin, I felt fatigued, and an EBV test suggested a recent infection. But my doctor diagnosed me with Gilbert's Syndrome, a fairly common genetic unconjugated hyperbilirubinemia that affects somewhere between 5 and 10% of the population. I plan to have my bilirubin tested again in six months or so. If it is still elevated, I may confirm the diagnosis through a genetic test that the University of Chicago offers <a href= "http://genes.uchicag...bert.pdf">(link)</a>. Here's a little more on the genetic basis for Gilbert's.

Until relatively recently bilirubin was viewed as a toxin. However, it is now seen as a potent antioxidant (link), even more potent than glutathione. From the last link:

"While it takes one glutathione molecule to consume an oxidant, a single bilirubin molecule can take care of 10,000 oxidant molecules, the scientists found."

So perhaps Gilbert's Syndrome is a desirable mutation and should be among genes considered longevity genes. There are studies that show a correlation between Gilbert's Syndrome and lower incidence of certain diseases such as arteriosclerosis and cancer (link).

Here's an interesting patent that discusses bilirubin and reduced all-cause mortality observed in men with Gilbert's Syndrome.

Interestingly, fasting can cause hyperbilirubinemia (link). I wonder whether this may be one of the reasons that fasting has demonstrated health benefits.

Does this interest anyone?

[CobaltThoriumG]

By the way - you may find this link usefull: http://www.gilbertssyndrome.com/

Cheers

Alex

Thanks. I guess after reviewing the long list of symptoms associated with Gilbert's Syndrome, it might be more accurate to characterize it as a mixed blessing than an entirely beneficial mutation. But of those listed, I have only occasional fatigue and some memory issues. But I doubt there's any way to be certain those are attributable to GS as opposed to something else.

[CobaltThoriumG]

Another question I have concerning Gilbert's Syndrome is how it may relate to resveratrol metabolism because of the 70% reduction in the glucuronidation enzyme referred to here.

Would a person with GS require a lower dose of resveratrol? Would resveratrol cause an elevation in bilirubin for those with GS? For my first blood test I was taking resveratrol, and at that time my total bilirubin was 3.1 mg/dL. About two months later when I had stopped taking resveratrol for about six weeks, my total bilirubin was 2.4 mg/dL. I was only taking 200 mg/day. I'm skeptical there is any connection. At some point I plan to resume resveratrol and I will be interested to see whether my bilirubin increases. The topic of resveratrol and bilirubin has recently been discussed in this thread.

Another question, if you knew you had double the normal level of bilirubin, given that it is so potent an antioxidant, would you take less or no additional antioxidant supplements?

Edited by CobaltThoriumG, 22 September 2008 - 04:08 PM.

[brotherx]

Not so much is known yet about Bilirubin and its possibilities as a strong antioxidant. Therefore I am just talking my supplements as usual. Most of my antioxidants I get from my nutrition anyhow.

Cheers

Alex

Another question I have concerning Gilbert's Syndrome is how it may relate to resveratrol metabolism because of the 70% reduction in the glucuronidation enzyme referred to here.

Would a person with GS require a lower dose of resveratrol? Would resveratrol cause an elevation in bilirubin for those with GS? For my first blood test I was taking resveratrol, and at that time my total bilirubin was 3.1 mg/dL. About two months later when I had stopped taking resveratrol for about six weeks, my total bilirubin was 2.4 mg/dL. I was only taking 200 mg/day. I'm skeptical there is any connection. At some point I plan to resume resveratrol and I will be interested to see whether my bilirubin increases. The topic of resveratrol and bilirubin has recently been discussed in this thread.

Another question, if you knew you had double the normal level of bilirubin, given that it is so potent an antioxidant, would you take less or no additional antioxidant supplements?

[davidd]

Does this interest anyone?

It certainly interests me!

ColbaltThoriumG and I have discussed this in PMs a bit. I'd like to also add that I think quercetin may be an important tool in regulating bilirubin levels. In addition to the link he included to my post in the resveratrol forums, here is one where I go into more detail on how long it took for my bilirubin to increase after stopping the quercetin supplementation. Quercetin has its own benefits as well, so it may be of interest even if not being used to lower bilirubin.

Also, here is an update to my original post, where I clear up the role that alcohol plays in reducing bilirubin levels (near the end). It also discusses my high iron intake to battle Gilbert's Syndrome and why I wouldn't recommend it to anyone now that I've found quercetin and considering how hard iron is on the body in large doses.

Most recently, I've found that drinking more water seems to have a positive effect on bilirubin levels. I've read about dehydration being correlated with higher bilirubin levels in the past and as this page points out, it may be even more important for those with Gilbert's Syndrome.

"Bilirubin levels tend particularly to be increased in Gilbert syndrome with starvation or dehydration."

I usually get about 2 cups of water in the morning, 2 cups of some type of liquid at lunch (usually milk), and 2 cups of liquid at dinner (milk or water or juice). That's what I used to average during the work week. In the past week, I've been trying to drink an extra 4 cups of water between breakfast and lunch. According to this page on dehydration, at 10 cups per day, I'm still a couple cups shy of what they recommend for someone with low activity levels.

Anyway, hydration is my most recent tool in my small arsenal against Gilbert's Syndrome.

As ColbaltThoriumG points out, however, bilirubin can also be a very good thing for our bodies. I'm currently in a bit of an internal battle with myself over whether I should truly try to lower my bilirubin levels. *If* I can find a way to fine tune my levels, I think I may settle on trying to keep it somewhere between 1.5-2.0 mg/dL. Normal range is 0.2-1.3 mg/dL. I'm guessing that may provide me with a reasonable reduction in fatigue, yet still plenty of antioxidant benefit.

Thanks for starting this thread, ColbaltThoriumG!

David

[davidd]

Another question I have concerning Gilbert's Syndrome is how it may relate to resveratrol metabolism because of the 70% reduction in the glucuronidation enzyme referred to here.

Would a person with GS require a lower dose of resveratrol? Would resveratrol cause an elevation in bilirubin for those with GS? For my first blood test I was taking resveratrol, and at that time my total bilirubin was 3.1 mg/dL. About two months later when I had stopped taking resveratrol for about six weeks, my total bilirubin was 2.4 mg/dL. I was only taking 200 mg/day. I'm skeptical there is any connection. At some point I plan to resume resveratrol and I will be interested to see whether my bilirubin increases. The topic of resveratrol and bilirubin has recently been discussed in this thread.

Another question, if you knew you had double the normal level of bilirubin, given that it is so potent an antioxidant, would you take less or no additional antioxidant supplements?

My guess is that a person with GS may get more resveratrol, due to the lower metabolization activity of UGT1A1. However, I've read a study that shows UGT1A9 is supposed to play a bigger role (not sure how much more) than UGT1A1. ("In recombinant human UGT supersomes, for both glucuronides, UGT1A9 exhibited higher activity than UGT1A1, whereas the lowest activity was observed with UGT1A10.") If you take enough resveratrol, UGT1A9 may encounter substrate inhibition (can't find the study right now where I read this), but I've also read that both UGT1A1 and UGT1A9 may face substrate inhibition, so it is unclear to me what's really going on.

I *seem* to have gotten good mitochondrial biogenesis from a relatively low dose of resveratrol (400 mg daily in 2 equal doses, morning/evening, but since upped to 600 mg daily). My personal anecdotal testing has not seemed to show an increase in bilirubin from resveratrol usage. I could be wrong, since it isn't based on measuring bilirubin levels over time. I *can* say that when I was taking resveratrol and quercetein, my bilirubin was relatively low (1.5 mg/dL). Since I stopped the quercetin and have only taken resveratrol, I believe my levels have increased, but I don't know what the value is. I doesn't seem to me that it is higher than it was before I started resveratrol/quercetin supplementation.

Regarding the antioxidant question... Different antioxidants take care of different reactive oxygen species. And some antioxidants have been shown to be harmful in the long run ("Antioxidant Vitamins May Increase Mortality" -- I'd probably stay away from Vitamin A supplementation based on that study.) It doesn't appear that bilirubin is harmful in the amounts we are talking about -- quite the contrary, since it has been shown to decrease all-cause mortality. The question would be, what other antioxidants are beneficial in the long run and perform different functions than bilirubin?

From wikipedia:

"The reactive oxygen species produced in cells include hydrogen peroxide (H₂O₂), hypochlorous acid (HClO), and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O₂⁻).^[12] The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in metal-catalyzed redox reactions such as the Fenton reaction.^[13] These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins.^[9] Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms,^[14][15] while damage to proteins causes enzyme inhibition, denaturation and protein degradation.^[16]"

From this (I also included the text below), we see that bilirubin appears to be good at scavenging hydroxyl radicals. It would make sense that something that can reduce the above hydroxyl chain of events from happening would be good for your long-term health.


Text from one of the links above (http://www.find-heal...uma-reflect.htm). Good stuff! I have to believe it is better to have the bilirubin ready and waiting than to rely on the body to produce more in a time of need.


Elevated plasma levels of bilirubin in patients with neurotrauma reflect its pathophysiological role in free radical scavenging.

Full Abstract
Bilirubin, a powerful endogenous antioxidant, is one of the catabolites of heme oxygenases (HOs). In this study, the plasma bilirubin concentration was measured to establish bilirubin kinesis after traumatic brain injury (TBI). Furthermore, in in vitro studies, the free radical scavenging activity and antioxidant potency of bilirubin was also investigated at various concentrations, including physiological ones. Indirect plasma bilirubin was measured in 25 patients on days 1, 2, 3 and 4 after presentation with TBI. The ability of bilirubin to scavenge the hydroxyl (OH) and 1,1-diphenyl-2-picrylhyrazyl (DPPH) radicals, and its antioxidant potency, were also analyzed using electron spin resonance (ESR) and the bioantioxidant power (BAP) methods, respectively. Plasma bilirubin levels were significantly higher on days 2, 3 and 4 than on patient admission (day 1; p < 0.05). ESR and BAP results revealed that bilirubin has direct OH and DPPH radical scavenging activities and potent antioxidant effects in vitro at physiological concentrations. These data indicate that physiological concentrations of bilirubin have antioxidant properties and that it constitutes one of the biological defense mechanisms in neurotrauma patients.


This is a good page discussing other antioxidants. It discusses bilirubin, among others. Hopefully we can come to some informed decisions on what other antioxidants may fill the gaps not handled by our excess bilirubin and add that information to this thread as we find them.

My current take is that we have a built-in antioxidant advantage. By using resveratrol supplementation to increase mitochondria numbers/size and to create mitochondria that don't produce as much reactive oxygen species, we may be well along the path to increased longevity and health.

David

[davidd]

Here is a good rundown on some of the studies that have been done regarding the relationship between bilirubin and human disease.

Unfortunately, it doesn't translate well when copied, so I'm not able to neatly paste it in here.

David

Edited by davidd, 19 October 2008 - 04:45 PM.

[davidd]

Most of the studies I read about showing that bilirubin is good for preventing cancer, heart disease, etc. relate to the theory that bilirubin protects against reactive oxygen species (ROS) damage (damage to DNA in the case of cancer and damage to artery walls in the case of atherosclerosis). The following is the first study I have come across that shows bilirubin acting directly on cancer cells to kill them.

...
Bilirubin exhibits a novel anti-cancer effect on human adenocarcinoma.
Rao P, Suzuki R, Mizobuchi S, Yamaguchi T, Sasaguri S.
Department of Thoracic and Cardiovascular Surgery and Regeneration Technology, Faculty of Medicine, Kochi University, Kochi, Japan.
Anti-oxidants are essential for intracellular free radical scavenging, as free radicals are one of the causes for tumorigenesis. Our objective was to use bilirubin and investigate its action on human carcinoma cell lines. Bilirubin manifested as a prooxidant showing its cytopathic effect on TMK-1, showing growth inhibition close to 50%. Cell cycle analysis showed an arrest at G0/G1. Flow cytometry investigations with Red CC-1 showed an increase by more than 2 times suggesting a prooxidative role of bilirubin. To check the effect of radicals on DNA, a Comet Assay displayed a typical comet's tail with bilirubin treated slides, only. Further, staining with DAPI showed apoptotic action of bilirubin. Decreased mitochondrial function by bilirubin was observed with Mitotracker Green FM staining. These unexpected data have led us to conclude that bilirubin has anti-cancer activity as a prooxidant and may have a more vital role in the human body than realized.
PMID: 16516158 [PubMed - indexed for MEDLINE]
...

One thing we may want to consider adding to this thread as we go is whether people with normal bilirubin conjugation can somehow simulate Gilbert's Syndrome if they desire to get the health benefits of increased bilirubin. A simple example, would be if their levels are on the low side of the normal range, and if they drink alcohol regularly, reducing alcohol consumption may bring their levels up, as alcohol may be inducing more enzymes from UGT1A1. This is just a guess on my part, as I don't know if alcohol has this effect on "normal" UGT1A1. It does have this effect on me and I've previously posted about mention in scientific literature backing this up.

I'll try to do some research on mechanisms to inhibit UGT1A1 and post what I find.

David

[luv2increase]

Too much of something good is always bad.


High bilirubin levels usually are a result of your liver not functioning correctly.

[brotherx]

There is the genetic variation which is called Gilbert Syndrom - which causes elevated Bilirubin - have a look at the beginning of this thread.
My liver is 100 per cent fine and I am absolutely healthy and heaving elevated Bilirubin (without any negative effects).

Too much of something good is always bad.


High bilirubin levels usually are a result of your liver not functioning correctly.

[davidd]

Too much of something good is always bad.


High bilirubin levels usually are a result of your liver not functioning correctly.

That's a good thing to clarify. We are discussing, primarily, an elevated level of unconjugated bilirubin from a genetic mutation. This particular mutation does not result in high enough levels to be considered harmful, and quite the contrary, appears to convey health benefits. There are other genetic mutations that result in much higher levels of bilirubin, which can shorten lifespan.

For example, Crigler-Najjar Syndrome, a very rare mutation (literally 1 in 1 million births), may lead to brain damage and/or death if not treated. The concentrations of bilirubin in this case may be anywhere from 6 to 50 mg/dL, depending on the specific type of the disorder. Above about 20 mg/dL is where it is generally considered more dangerous.

In the case of a completely normal person, the range would be about .2 to 1.3 mg/dL. Even being in the upper half of this range can show significant health benefits, according to studies that have been done, which were linked to above.

In the case of Gilbert's Syndrome, a less rare mutation (some say up to 5%, some say up to 10% of the population), bilirubin conjugation ability is decreased, but not to the level it is with Crigler-Najjar Syndrome. The range could be anywhere from 1 to 6 mg/dL, depending on a variety of factors present at the time.

To your point about liver malfunction causing high bilirubin levels... Although this may be true, I wouldn't say it is mostly the case. Although, technically, since UGT1A1 is mostly active in the liver, I guess you could say that even this issue is a "liver malfunction", but probably not the type to which you were referring.

A person should have a clear understanding of the cause of increased bilirubin before making any decisions regarding what to do about it. There are reasonable tests that can be done to identify whether Gilbert's Syndrome is the cause. And if someone wishes to spend the extra money, there are even genetic tests that can provide a positive identification of certain mutations involved in Gilbert's Syndrome.

So, to be clear, we are not talking about bilirubin levels that fall into the ranges that are considered dangerous. And we are not talking about levels that are increased due to non-enzymatic origins (liver cancer, for instance, may raise levels). We are talking about levels that are normal or a few mg/dL above normal.

In my previous post, I was discussing how a person may either stay on the upper end of normal, or even exceed the normal range a little, with the possibility that doing so may convey certain health benefits. I don't think it would be possible for a normal person to increase their levels up to the dangerous zone. It isn't like there is a bilirubin supplement that can be taken to increase our levels. Rather, there is the chance of affecting gene UGT1A1 to increase or decrease enzyme production a bit, thus lowering or raising bilirubin levels.

In my case, I wish to lower my levels a bit to avoid some of the side effects I have at higher levels ("higher levels" is probably above 2 mg/dL for me). Others may wish to increase their levels, especially if they are below .6 mg/dL. It is all relative. Having levels below .6 doesn't guarantee problems and me having high levels doesn't guarantee that I'll be free from cancer or atherosclerosis, but it does appear to predispose someone one way or the other to a certain degree.

David

Edited by davidd, 20 October 2008 - 02:42 PM.

[davidd]

First off, here is another study (actually a meta-analysis of other studies) showing that increased bilirubin is related to decreased risk of atherosclerosis.

http://www.ebmonline...tract/228/5/568

...

Inverse Relationship Between Serum Bilirubin and Atherosclerosis in Men: A Meta-Analysis of Published Studies
Ladislav Novotn^* and Libor Vítek<sup>,1

*</sup> EuroMISE Center-Cardio and Institute of Hygienic Medicine and Epidemiology, and
4th Department of Internal Medicine and Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Medical Faculty, Charles University, Prague, Czech Republic

Abstract

Bilirubin, a major intravascular product of heme catabolism, is a potent antioxidant compound. Numerous studies have been published showing the relationship between serum bilirubin levels and atherosclerosis. In the present investigation all the epidemiological studies available on the effect of serum bilirubin levels and atherosclerotic disease were analyzed. Studies on the epidemiology of atherosclerotic diseases in relation to serum bilirubin levels were searched in the MEDLINE database. Selected studies were subdivided according to serum bilirubin levels and severity of atherosclerotic disease. Because of the limited number of females involved in the studies, only males were included into meta-analysis. Associations for ordered categorical variables (bilirubin and natural history of graded atherosclerosis) were assessed to find correlation and linear trend between analyzed variables. A stratified analysis was conducted to compare risks of clinical outcomes. Eleven relevant studies were used for analysis. A close negative relationship was found between serum bilirubin levels and severity of atherosclerosis (Spearman rank coefficient r = -0.31,P < 0.0001). The linear trend was confirmed in analysis of proportions with x² values for both disease conditions to be very significant (P < 0.0001). Unambiguous inverse relationship between serum bilirubin levels and atherosclerosis was demonstrated in this preliminary meta-analytic study. These results indicate the importance of hem oxygenase-related products in the prevention of oxidative stress-mediated diseases.

Key Words: atherosclerosis • oxidative stress • ischemia • artery disease
...


To be fair, there are still questions about whether it is the increased bilirubin or the increased heme oxygenase (the enzyme that breaks down the red blood cells to start the process that produces bilirubin eventually) that is responsible for reduced atherosclerosis. Now those with Gilbert's Syndrome, depending on their specific mutation, may have both a decrease in bilirubin conjugation as well as an increase in bilirubin production (through extra heme oxygenase activity). This is documented in the following study.

<A href="http://www.ncbi.nlm....pubmed/11915038

...



Hemolysis and bilirubin conjugation in association with UDP-glucuronosyltransferase 1A1 promoter polymorphism.
Kaplan M, Hammerman C, Rubaltelli FF, Vilei MT, Levy-Lahad E, Renbaum P, Vreman HJ, Stevenson DK, Muraca M.Department of Neonatology, Clinical Genetics Service, Shaare Zedek Medical Center, Faculty of Medicine of the Hebrew University, Jerusalem, Israel. kaplan@cc.huji.ac.il

Hemolysis may contribute to hyperbilirubinemia in Gilbert's syndrome. The authors examined blood carboxyhemoglobin corrected for inspired CO (COHbc) to index heme catabolism and serum conjugated bilirubin fractions to reflect bilirubin conjugation. Both parameters were related to UDP-glucuronosyltransferase 1A1 (UGT) promoter polymorphism, associated with Gilbert's syndrome, in term male newborns. COHbc was expressed as percentage of total hemoglobin, and total conjugated bilirubin (TCB) value as a percentage of serum total bilirubin (STB), (TCB/STB[%]). A production/conjugation index, COHbc/(TCB/STB[%]), represented bilirubin production divided by conjugation. UGT promoter genotype was designated according to the number of promoter TA insertions in each allele: 6/6, homozygous normal; 6/7, heterozygous; 7/7, homozygous variant. STB and COHbc values were higher in the 7/7 subgroup than the other counterparts (P <.01). The COHbc/(TCB/STB[%]) was higher in the 7/7 than either the 6/6 or 6/7 subsets (1.93 [1.31-2.88] vs. 0.85 [0.51-1.72] and 0.84 [0.53-1.87], respectively; P <.01). In conclusion, 7/7 UGT promoter polymorphism was associated with increased blood COHbc values (unexpected finding) as well as diminished serum total conjugated bilirubin ratios (expected finding). The increased hemolysis may contribute to the pathogenesis of increased STB values seen in Gilbert's syndrome, and exacerbate neonatal hyperbilirubinemia associated with the promoter polymorphism.
...


I recently had an EBCT (electron beam computed tomography) scan done to assess my atherosclerosis level. I just got the results and they rate me with a score of zero. From this page on identifying asymptomatic coronary artery disease, we get the following information on what the scores mean.

...


<H3 class=dynamic>How Do I Interpret My Coronary Calcium Score?</H3>

• 0 - No plaque is present. There is less than a 5% chance of having heart disease. Risk of a heart attack is very low.
• 1 – 10 - A small amount of plaque is present. There is less than a 10% chance of having heart disease. Risk of a heart attack is low.
• 11 – 100 - Plaque is present. There is mild heart disease. The chance of a heart attack is moderate.
• 101 – 400 - A moderate amount of plaque is present. There is heart disease; plaque may be blocking an artery. The chance of a heart attack is moderate to high. Your health professional may want to do more tests and may start treatment for heart disease. Aggressive treatment may be started for risk factors such as high blood pressure and high cholesterol.
• Over 400 - A large amount of plaque is present. There is more than a 90% chance that plaque is blocking one of the arteries. The chance of a heart attack is high. Your health professional will want to do more tests and will start treatment.

<H3 class=dynamic>What Are The Risks Of Having A Heart Scan?</H3>

• Critics raise the issue of false negative results in heart scanning especially in younger populations. A negative result may not detect soft plaques.
• Although calculated risk is present, actual risk (of course) cannot and is not and must be assumed as such. Critics note that further invasive tests may be performed (cardiac catherization and/or angioplasty).
• CT scanning increases radiation exposure comparable to multiple chest x-rays.

<H3 class=dynamic>What Are The Benefits?</H3>

• Knowing your risk.
• Dependent on the results, identifying the risk of cardiac event in the immediate future spurs lifestyle changes and fosters a proactive approach by both the patient and the physician towards targeted medical prevention and/or timely intervention.

...


Now, one of the reasons I had the test done (probably the main reason) is that my father has been told that he has higher than expected atherosclerosis, given his level of cholesterol (which isn't low, but isn't extremely high either). I wanted to see if I was genetically predisposed to atherosclerosis. I theorized that if I was, I might show some level of build-up, even though I'm only 37 years old.

As the test shows, I have no plaque present (that can be detected with this test -- might still have non-calcium plaques). However, according to the information I was given with the results, it has statistics showing that 80% of people my age have a score of zero.

Personal analsysis:

1) I could have the same issue that my father has, but my Gilbert's Syndrome is countering it, thus I have no atherosclerosis.

2) I could have the same issue that my father has, but the issue may not show build up at my age, even if I didn't have Gilbert's Syndrome.

3) I could not have the same issue that my father has and even without Gilbert's Syndrome, I'd have an 80% chance of having a score of zero.

4) I could not have the same issue that my father has, and the Gilbert's Syndrome is helping me stay within the 80% percentile.

In other words, this test really says nothing conclusively about my personal relationship between Gilbert's Syndrome and atherosclerosis. It does provide peace of mind that I don't show calcification of my arteries at this point in my life. The other reason I may have had some concerns is that my HDL cholesterol levels are lower than I'd like (35 and 32 mg/dL in my last two tests in the last 4 months, which is lower than the bottom end of "normal", with normal being 40-50 mg/dL).

I should also add that my self assessment that I gave to the technicians was a rating of 2/10 on how much I exercise and 5/10 on how low fat my diet is. In other words, very little exercise and middle of the road fat content. I do plan on increasing my exercise when I'm done with some other personal tests regarding resveratrol mitochondrial biogenesis potential that exercise may confound.

My current plan is to have this test done once every 5 years. By keeping an eye on this, I hope to get an early handle on atherosclerosis if it does begin to rise. It is normal for it to rise as you age, but I'd much rather be abnormal in this regard, to increase my chances of longevity.

If anyone reading this who has Gilbert's Syndrome and who is older has this test done, I'd be very interested in the results.

David

[davidd]

I posted in another thread about Gilbert's Syndrome. It may be of benefit to people reading this thread, so I'm providing a link to it here.

http://www.imminst.o...&...st&p=272861

Notably, I included my latest findings on what may increase or decrease bilirubin levels.

David