A number of your symptoms are consistent with symptoms reported by people with Gilbert's Syndrome (GS). However, you won't find a lot of the symptoms listed in medical literature for the condition. Some of the symptoms you listed were fatigue, brain fog, mild dyslexia, lack of motivation and dysnomia (trouble recalling words and/or names). I can relate to those symptoms and I can relate to some of your college experiences, although I believe yours is a more serious situation. I have Gilbert's Syndrome.
In brief, GS is a genetic mutation that causes less of a specific liver enzyme to be produced. This liver enzyme metabolizes bilirubin (produced when red blood cells are destroyed), so people with GS usually have higher than normal levels of unconjugated bilirubin in their blood. This can show up as jaundice, especially during times of illness or other stress. Besides not processing bilirubin as rapidly as normal, there can be drug interactions, where drug doses are effectively increased due to the slower metabolization in this particular enzyme (slower due to amount, not due to a functional change in the enzyme itself). For instance, some chemotherapy drugs need to be given in smaller doses for people with Gilbert's Syndrome to prevent over-toxicity. Even something as common as aspirin is most often metabolized more slowly in people with GS. GS is present in about 5-10% of the populate. It is usually found in the teenage years or early adulthood when a test is ordered for some reason and the bilirubin is noticed. I think there is something hormonal that causes bilirubin production to increase at this point in life, so although the mutation is there from birth, it may not affect someone until the bilirubin production is increased.
From my light research on the matter I am inclined to think you and others may be right -- there may be consequences of the syndrome, neurological tendencies even, which are not recognized by the medical community at present.
So understanding that I speak on hypothetical ground, I'm curious -- what are treatments for Gilbert's Syndrome? Lifestyle changes? Any supplements that show an effect?
Disclaimer: If you do want to act on anything I've mentioned, please discuss it with your physician first. I am not a physician.
First off, there is some cross-over information in another thread on the boards. However, that deals mainly with
the health benefits of extra bilirubin rather than the possible negative aspects, so in the context of negative symptoms, I'll keep the reply in this thread.
It is a tricky thing, because who knows whether all these things are just from Gilbert's Syndrome, or are a combination of that and other things. It makes me wonder just how many genetic mutations there are that are unknown, and that affect small, but significant subsets of the population. This particular mutation was not discovered until 1996. Even within Gilbert's Syndrome, there are genetic variations among different people.
As for treatments, there are no real recognized treatments. The medical community considers Gilbert's Syndrome to be largely inconsequential. For those less fortunate people, who have Crigler-Najjar syndrome type II (same general issue as Gilbert's Syndrome, but even higher levels of bilirubin), they can be given phenobarbital daily to reduce some of the bilirubin -- down to about the same level as Gilbert's Syndrome. People with Gilbert's Syndrome can take this too, and then the bilirubin levels may be normal, but it probably isn't a good long-term plan.
Keep in mind that what may increase (or decrease) bilirubin may not increase/decrease the symptoms, because it may be that some of the symptoms are not directly related to the bilirubin. However, that's really all we have to go by, so my theory is to try to stay away from things that raise bilirubin and consider adding things that reduce bilirubin.
I'll get back to possible "treatments" in a minute. First, let's discuss what may exacerbate the hyperbilirubinemia.
Fasting for 48 hours may raise bilirubin levels by a factor of 2 or 3 in people with GS. Therefore, eating regular meals is a good thing and skipping meals (especially breakfast) would theoretically be a bad thing. Speaking from experience, I can say this seems to hold true for me. Not that I know what my bilirubin level is when I miss a meal, but I feel worse if I don't eat regularly.
I've also read that low fat diets (about 5% or less fat) can raise bilirubin levels the same amount as a complete fast. I'm not sure if medical science knows why exactly this happens. Keeping the fat to 10% or higher supposedly avoids this issue.
Niacin (Vitamin B3) can raise bilirubin levels in people with GS by a factor of 2 or 3, in doses of 50 mg, within just a few hours. I'm not sure what taking the RDA of B3 does, but if I remember correctly, this is 2.5 times the RDA. So maybe sticking with the RDA is wise. I think it is also believed that taking higher amounts of B3 with other B vitamins and vitamin C may reduce this effect, but I don't know if that is valid or not. Just something to keep in mind if you do happen to have GS and have high cholesterol and a doctor tells you to take B3 for the cholesterol/triglycerides.
Now even though it contains less than the RDA of niacin, I do try to stay away from chicken/turkey for lunch, as it really does seem to make me sleepy. I always just figured I was especially sensitive to tryptophan, which really shouldn't make most people sleepy when consumed in food form. Oddly enough tryptophan is converted into niacin in the body. The link between tryptophan and niacin and niacin and Gilbert's Syndrome is an intriguing one, but hard to say how much effect I truly have from chicken/turkey as a result of GS.
Now, the above may be the documented things that raise bilirubin (or lower in the case of phenobarbital) in people with GS, but I have to believe that anything that inhibits the production of the enzyme from UGT1A1 (glucuronyl transferase) is going to be a bad thing for GS. There is a bit of a debate about fluoride's enzyme inhibiting abilities and that it may be extra bad for people with GS. To be on the safe side, one might want to consider staying away from fluoridated water. That also has the benefit of staying away from chlorine, although a lot of that is absorbed just by taking a bath/shower if you have chlorinated water. :(
On the flip side, anything that induces the production of glucuronyl transferase should be a good thing (in theory). Not only is it going to reduce the amount of unconjugated bilirubin in the blood, but it is also going to help in the metabolization of some drugs and in the removal of other toxic chemicals from the body.
There are a number of things that are supposed to induce UGT1A1 (besides phenobarbital). Some of them are:
quercetin
chrysin
acacetin
apigenin
luteolin
diosmetin
Those are all flavonoids. There are other flavonoids that may help as well, but those are the ones in my list of things to consider currently. For some reason, although flavonoids can be very good for you, the body goes into overdrive to flush them out of your system. It does this by increasing production of the detoxifying enzymes, such as glucuronyl transferase.
Side note: UGT1A1 is one of the two main genes (along with UGT1A9) responsible for phase 2 metabolization of resveratrol, which a lot of people on this board take. It is interesting that resveratrol's polyphenol cousins would act to eliminate it from the human body. In the case of GS, however, I wonder if the best of both worlds can be had, since reduced metabolization of both the flavonoids and the resveratrol may allow them to do more of the good that they have shown in test tubes. I should also point out that the metabolites of some of the flavonoids have also been shown to be beneficial (anti-cancer, etc.), so even if they are quickly metabolized, it doesn't mean they aren't doing you any good.
Alcohol has been shown to induce UGT1A1 too. Obviously, there are downsides to alcohol consumption, but if a person can treat this more like a supplement and take a measured dose each day, there may be some benefits for those with GS. A lot of people with GS state that they feel more ill than usual when they consume alcohol. Maybe some people have other mutations that cause this, or maybe it is just that when they drink a lot, they are staying up late and not getting as much sleep. Lack of a good night's sleep seems to be a common agitator for this affliction. I'll also mention that I have a theory that a lot of people aren't diagnosed with GS, or aren't diagnosed as early as they otherwise would be, because of relatively frequent alcohol consumption masking the hyperbilirubinemia on the blood tests.
Lastly, prolonged exposure to light, especially blue light, over a large percentage of your skin, can reduce bilirubin concentrations. Unlike the UGT1A1 inducers, this works by converting the bilirubin into a water-soluble isomer, called lumirubin, which can then be excreted by the kidneys. In effect, the light is doing the job of UGT1A1. However, it is only doing UGT1A1's job with respect to bilirubin. It isn't removing other toxins (unless they happen to also be light sensitive). That goes back to my comment about whether lowering bilirubin levels alone is all that is needed to reduce all the GS symptoms.
Light therapy is used for jaundiced babies (depending on the bilirubin levels) and is also the only therapy I know of for Crigler-Najjar Syndrome type I. People with type I have almost no bilirubin conjugation ability, thus they have toxic levels of bilirubin in their blood. They will usually sleep, uncovered, under blue lights. If they don't do this or don't have liver transplants, they will die at some point.
The above information is a good amount to get you started.
Most of it is based on scientific studies. I will now tell you briefly about what I do and my personal recommendations for someone with GS. Each person is unique, so what works for me may not work for someone else.
I have only noticed 3 things that have helped me. Iron supplementation, alcohol consumption, and quercetin supplementation. The iron was tried on a hunch, due to the fatigue, even though blood tests didn't show me as being anemic. I did this for a few years, but I wouldn't recommend it, because iron is just too hard on your body. It helped with my fatigue, but I don't think it did anything for the bilirubin levels, so the other symptoms were still there. As for the alcohol, it is just something I noticed. I rarely drink alcohol, but I noticed that I would wake early and quickly (very rare for me) when I drank the night before. Even just a couple beers seemed to have this effect. I also noticed that my eyes were nice and white the next day. My eyes aren't typically ultra yellow, but they aren't bright white either. It wasn't until recently that I found the scientific information about how alcohol induces UGT1A1. Like iron, I don't personally consider alcohol a good solution.
Earlier this summer, when I was looking into resveratrol, I read how some people experienced more energy when they started taking it. I researched it a bit and although there is some controversy about this, I decided to take quercetin with it. I also decided to take a quercetin supplement that contains a plant enzyme called bromelain (comes from the stems of pineapples), since that was supposed to help absorption/bioavailability.
So, I stopped taking extra iron supplements (but did keep taking a multivitamin twice a day that contains iron), and started taking 400 mg resveratrol (it also contains grape seed extract, grape skin extract and pine bark extract) and 1000 mg quercetin (which included 500 mg bromelain). This was taken in two divided doses -- once in the morning and once in the evening, with breakfast and dinner, respectively. I felt really good, but had a hunch that a little more quercetin would be even better, so I upped it to 1500 mg of quercetin (750 mg bromelain) after about a week. This was still in line with what the bottle recommended taking and my research showed that there wasn't very much risk of toxicity with quercetin or bromelain.
Although I felt the effects the first day, I'd guess it took about two weeks with this combination before I felt the full effects, which included a reduction in some nagging aches and pains I had (my guess is they were from the iron supplementation) in addition to much less lethargy, being able to wake early, etc. Quercetin and bromelain are anti-inflammatory, so that makes sense. Of course, I had no idea which of the 3 supplements were responsible for all the changes.
After about 8 weeks, I ran out of resveratrol. When I received my shipment, I decided to try taking just the resveratrol and to stop taking the quercetin/bromelain. I also increased the resveratrol from 400 mg to 600 mg daily (still in two doses). About two weeks after doing this, my jaundice started coming back (my indirect way to measure the bilirubin), as did my fatigue. Slowly, over another 6 weeks or so, the aches and pains came back too. This leaves me believing that it was probably the quercetin that reduced my GS symptoms and the mixture of quercetin/bromelain that helped with the aches and pains (I'll give bromelain the bulk of this benefit). It is possible it was the combination of the 3 supplements that helped with my GS symptoms, but my money is on the quercetin, given the scientific knowledge I now have, much of which was acquired over this summer from scouring the Internet.
I'm doing some unrelated testing of resveratrol's mitochondrial biogenesis potential, but will start taking the quercetin/bromelain again at some point. I also plan on getting a
blood test with and without the quercetin supplementation to note the differences in bilirubin concentration and other metrics. I do have bilirubin results from earlier this summer when I was taking it. My total bilirubin (which was 100% unconjugated) was just barely above normal, at 1.5 mg/dL (normal is 0.2-1.3 mg/dL). From memory, I've had it tested as high as over 3.x and as low as 2.x in the past. This low result (1.5) give me more proof that the quercetin really was lowering my bilirubin and not that I just felt better for other reasons.
Given the above, I recommend people with GS at least try the quercetin/bromelain combo. Seems to be little risk and a lot to gain. It is also relatively cheap.
I also recommend having a consistent eating schedule that contains at least 10% fats and a consistent sleeping schedule, with at least 8 hours of good sleep.
I recommend not taking acetaminophen (Tylenol). I believe the risk of liver damage is not worth it. Many people with GS also have mutations in other genes responsible for metabolism of this chemical. This can, in theory, leave the drug in the liver too long, causing damage. Oddly enough, my drug of choice has always been ibuprofen. I don't take aspirin or Tylenol, because they don't seem to work as well for me for headaches. I am not aware of any problems with ibuprofen and GS. I can also count on one or two hands how many ibuprofen I take in a typical year.
As you can probably guess from the above, I don't do drugs. This isn't because of GS. However, I have to believe that there might be some risks with drugs (illicit or not) for people with GS. I have a hunch that marijuana and Gilbert's Syndrome don't mix. It seems like the symptoms/side effects overlap, thus could be exacerbated when combined. There's no scientific backing for that, just my personal guess.
Feel free to ask me if there are any questions about anything I've posted, whether through the thread or in a private message.
David
LongeCity
