Earlier this year at a Mental Health Training for IM doctors, 3 practitioners (myself, a doctor & a psychiatrist) walked into a bar…not really, but we did each present a case study of challenging patient & in whom we had some great outcomes. All 3 patients presented happened to have Gilbert’s Syndrome. Just in case you’re wondering if there was a secret Gilbert Syndrome Conference you didn’t get an invite to, no. Or that perhaps there was premeditation and intention on the organisers behalf for a bit of sub-theme and focus, no. While this was purely coincidental it does speak rather loudly to a couple of things though.
Patients with Gilbert’s syndrome are likely to be over-represented in our client base especially among those presenting with psychiatric and/or gut issues (and both presentations frustratingly for them, very hard to diagnose, define, pigeon hole etc) and secondly, even though their genes underpin their biological susceptibility to such health problems, great outcomes are really possible.
One of the challenges comes from the medical dismissiveness of this genetic issue as simply ‘benign hyperbilirubinemia’. This has lead to a lack of diagnosis in patients affected and when it is incidentally picked up on routine bloods, a lack of follow up education about what having approx. 30% less phase 2 glucuronidation activity, in their gut and their liver, is really likely to mean, not to mention radically altered bile composition and digestion (!) and how they can make better choices in light of this. Similarly this year in our Mental Health Specialist Mentoring Group, the issue of reduced efficacy and tolerance of psychiatric medications, in those with Gilbert’s, raised its head over and over again. Given that so many drugs within the psychiatric class add at the very least to the ‘substrate load’ of the UGT system, if not frankly inhibit some members of this enzyme family, as this paper (check out Table 2…superb!) shared by my colleague, Kate Worsfold, points out, it actually shouldn’t come as a surprise.
But there is a change a’coming with an influx of research leading to improved understanding of this seemingly mercurial malady, resolving many riddles, identifying new key ways to help these patients and at last….some exceptionally good news for those with Gilbert’s.
For example, when I started this conversation back in 2013 with the Update in Under 30 Gilbert’s Girls, that was in response to seeing so many women at the time presenting with significant imbalances in both their sex hormones and their neurobiology as a result of their UGT impairment. But of course it was never meant to imply GS is just a girl thing! In fact there is a 3:1 dominance of men with this condition and some very good reasons as to why: more red blood cells and more testosterone…the former being the primary source of bilirubin and the later a terrifically powerful UGT inhibitor. The news from the research frontier is nothing short of thrilling, rewriting our thoughts on what medications and supplements (!!) are the most problematic, improved dietary management, how to track their progress more accurately and why completely normalising their bilirubin is not the goal…hey did someone say…longer telomeres?! 😉
The latest Update in Under 30 has landed: Gilbert’s – New Goals and Good News and my team has gone all out in producing a brilliant desktop reference to go with this recording that aids better understanding and clear treatment aims for your GS patients.
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I take my job to heart. When someone asked me recently to choose the single value that spoke most to me personally I couldn’t seem to go past, ‘Purpose’. I feel very honoured to have contributed to the learning of so many health professionals in their undergraduate and so many more in their professional careers following graduation and I know that with this comes huge responsibility. Second on my values list (again, possibly unsurprising) is Empowerment & coming in with a photo finish at 3rd: Integrity. Discernment and critical thinking (about information, about research, about reflective practice) are perhaps the eggs in this souffle, helping us all to rise up.
As part of our critical thinking we need to accept a few truisms:
Research changes Experience changes Knowledge changes
Information is not static. So we need to ask ourselves, how long ago did I learn this? How long since I’ve checked it is still correct? And just because perhaps this information came out of the mouth of our mentors or teachers, makes it no less up for regular review. I’m trying to undertake these internal audits on a regular basis. Typically they’re prompted by bloody good questions my mentees have asked me. A question I can’t answer or, more to the point, I can’t answer with full confidence I’ve double-checked my old beliefs and understandings against new evidence recently…these almost always provoke a lost night of sleep for me. Not from sleeplessness per se but due to immersing myself in the latest research and performing a mini informal lit review, bringing out all my old beliefs/evidence etc. Marie Kondo style and asking do they still spark joy✨ (in light of the latest evidence)?! And yes sometimes there’s a little bit of heartache when you have to let your old tightly held beliefs and understandings go 😢
The 1st update is about N-acetyl cysteine. Some of you may have heard me previously question the efficacy of the vegan form. Now that all but 1 Australian product is vegan, produced from bacterial fermentation or purely synthetic, I was wayyyyyyyy overdue to check the validity of my old ideas. Let the record show, I was wrong. Unlike some other nutraceuticals like chondroitin sulphate, wherein the source radically changes the overall structure of the molecule and therefore its uptake and actions – the same is simply not true for NAC.
So those ducks, & their NAC rich feathers, can all sleep a little easier at last…phew! Now the 2nd internal audit well that did cause some tears for me…
Setting the record straight: The ABC of CDG
We often identify patients who could do with a little glucuronidation first aid: marked dysbiosis, Gilbert’s syndrome, oestrogen excess, cancer risk (especially bowel, breast & prostate) and one of our nutritional go-to’s has typically been Calcium D Glucurate. While there is ample evidence that one of CDG’s metabolites: 1,4 GL – inhibits beta-glucuronidase, is an antioxidant, platelet activation inhibitor and generally all-round good guy to have onboard, new research strongly challenges that oral CDG will convert to this at levels sufficient to support this detoxification pathway. Sounds like we’re overdue for an update on this supplement and when and where it might be useful in addition to how to find the real deal in real food!
When a teenage girl presents seeking her first oral contraceptive pill (OCP) script, what information is she privy to that enables her to make an informed decision? Read the insert inside the box? Please. Which 50 year old, let alone 15 year old does that? Forget it! What might her doctor tell her? Perhaps about clotting risk, as part of their determination of the suitability of this form of contraception for her but is there any discussion about the potential for adverse mood effects? A recent study of over 1,000 teenage girls followed over more than a decade adds to other evidence that suggests this should be flagged as a consideration prior to the prescription being written.
Most integrative health practitioners not only know about the potential negative impact on mood from OCP use in women but we’ve observed firsthand the havoc it has wreaked in some teenage girls’ and women’s lives.
A very experienced practitioner I know says, ‘if I am hearing mood instability and then I see a significantly elevated serum copper and or cortisol in these girls that’s when I just say to have to say to them, you know I don’t think this is the best contraception for you!’
This latest study did not find higher rates of depression across all OCP users in this group of 16-25 year olds but when they looked at this at different ages they found its use increased depression scores and was associated specifically with more crying, eating problems and hypersomnia. The discussion around the enhanced vulnerability at this younger age compared with older girls centres on the relative immaturity of their CNS. But wait, I hear you critical thinking clinicians ask, perhaps those teenage girls had more depressive features prior to starting the OCP. Good thinking 99! And the answer is…maybe…but the relationship goes both ways: from the related Medscape Continuing Medical Educational Activity
“For 16-year-old girls, the association was weakened after adjusting for depressive symptoms before use of OCPs, but the findings remained significant. This suggests that the relationship between OCP use and depressive symptoms could be bidirectional…For instance, 16-year-old OCP users were more sexually active and had more stressful events, as well as more menstruation-related pain and acne, than their counterparts in the nonuser group. Analyses showed that all these factors weakened the association, although none diminished it.”
The commentary surrounding this latest study is essentially 1) this is not the first study to find an association and others have been more able to demonstrate that COCP use predated the mood disorder in those affected and 2) those exhibiting higher depressive scores did not actually score strongly for anhedonia or sadness which are the most typical features in adult depression – so perhaps we are missing some of these negatively impacted young women. Awareness regarding reproductive psychology is rapidly growing and in Australia we are fortunate to have emerging hubs to seek help and specialist advice in this area, such as the important work of Professor Jayashri Kulkarni and colleagues out of the Women’s Mental Health Clinic. I’ve referred patients, both when a patient’s mental health appears to be caused or aggravated by use of hormonal agents but which they can’t not use for various reasons and for those small number of women in whom I feel hormonal management may in fact offer a psychiatric solution. So again I am asking, while we know & mainstream medicine increasingly knows about this association…who’s telling these young women?
How many of your clients are on a combination OCP? Do you know the full extent of the physiological impact as a result and are you able to identify to key pathology indicators of the size of that impact?
We’re all aware that in theory OCP use correlates with a range of elevated risks but in reality many females will make the decision that the pros, in terms of contraception or control of acne etc., outweigh the cons. What if we could provide more individualised advice by looking to their pathology results and identifying and quantifying specific danger signs for each individual? This approach enables us to better support patients who chose this form of contraception and to accurately identify those that should be be encouraged to find other safer options more biochemically suited to them. Learn more here.
This year I heard a great quote that hit the spot for me: anyone who offers you a simple solution to a complex problem is lying or misguided, the solution to a complex problem will inherently be complex. Dang! I’m frequently reminded of this in relation to many different aspects of working in integrative health. Or even just answering work-related questions socially. Random-friend-I-haven’t-met- yet, upon finding out I work in nutrition, asks: Is [insert any given food, beverage, macronutrient, micronutrient] good for you? In spite of over 20 years of this happening, I confess, the poker face still requires concentration.
The poker face is necessary of course to
a) conceal my amusement at how predictable humans are and
b) to cushion the blow for them as I tear down the delusion that real nutritional science is simple and can be served up in a soundbyte or
c) lie and infer that it is, just to get out of there faster!
But recently, I’ve had another reminder of that ‘in here’ rather than ‘out there’, about how even as practitioners we long for things to be simpler than they are. This month in mentoring I’ve been talking about the dark side of both zinc and Akkermansia muciniphila (I know wash my mouth out right?!) in neurological issues. What, but we had them on the good guys list?! Remember the answer to a complex problem (and human health surely owns this territory) will inherently be complex, right? Similarly, I’ve been digging deep in research about beta-glucuronidase, that enzyme that undoes our phase 2 detoxification of oestrogen, bilirubin and a long list of nasty xenobiotics, earning it the informal title of ‘bad ass biomarker’…scoundrel! And well, I’ve found some really nice things to say about it…like actually it extends the half life of most of our flavonoids such as quercetin, isoflavones etc etc and that’s a great thing for increasing their positive punch given that their rapid detoxification limits how much we can benefit from them. Turns out, like everything else, even dear old beta-glucuronidase exhibits light and shade.
How I ended up losing a weekend to such papers was because I was trying to resolve some burning questions about Ca-D-glucurate (CDG) that I’ve had for as long as I’ve been recommending it to people who arguably could benefit from a little less beta-glucuronidase activity.
My two most pressing ones were: How much is required to be effective & Where’s the evidence?
And that’s when the fight broke out [just in my head] You see every review I’ve read, every piece of product information too, repeats the mantra CDG 500mg TID but turns out this is based on…not much. More uncomfortable still, is that even our assumption that we can convert CDG into its active form has been strongly challenged. The new research, which is not the work from the 1990s that everyone cites, is a must read…or if you actually have a life, and other ways to spend a weekend then maybe just spend 30 mins with me in my Update in Under 30 this month 😂 I wanted to keep it simple and neat and tidy. I tried I promise. But in the end…wouldn’t you know it…it’s complex.
So to bring everyone up to speed, including myself!, I recorded an UU30 on…
The ABC of CDG
We often identify patients who could do with a little glucuronidation first aid: marked dysbiosis, Gilbert’s syndrome, oestrogen excess, cancer risk (especially bowel, breast & prostate) and one of our nutritional go-to’s has typically been Calcium D Glucurate. While there is ample evidence that one of CDG’s metabolites : 1,4 GL – inhibits beta-glucuronidase, is an antioxidant, platelet activation inhibitor and generally all round good guy to have on board, new research strongly challenges that oral CDG will convert to this at levels sufficient to support our detoxification pathways. Sounds like we’re overdue for an update on this supplement and when and where it might be useful in addition to how to find the real deal in real food!
You can purchase The ABC of CDG here.
If you are an Update in Under 30 Subscriber, you will find it waiting for you in your online account after you have logged into your account.
*****Your RAN Online Account has a NEW LOOK!!*****
Next time your log in, you will experience a more user friendly way to search, view, listen and download your resources. Find out what’s new here.
Sometimes we wonder who put the invisible sign up out the front of our practice, right? The one that says…absolutely everyone with Condition ‘Z’ come and see me, now! I’m sure you know what I’m describing. Well this week I have hit the trifecta, performed a neat little hat-trick and diagnosed 3 patients with Gilbert’s Syndrome who all present in their own individual way but actually each one also with quite a textbook Gilbert’s picture, it almost beggars belief. Have a little look
70yo Female says: Since childhood she has felt like she has had a rock in her stomach after she eats. This ‘rock’ is there for hours. Her stools are never the same in spite of a regular diet and she has always been uptight and anxious. All her bilirubin results are in the 20s & she reports she’s ‘always’ had high values
55yo Male with severe ‘constitutional anxiety’ and surprisingly high oestrogen and a worrisome profile of oestrogen metabolites. His bilirubin is in the 20s
30yo something Female presents with unexplained severe unwellness for 20yrs that mostly involves nausea, bloating, a functional gut disorder without a real diagnosis, anxiety, depression and poor stress tolerance. Her bilirubin fluctuates between 30 to high 40s. (more…)
Duck duck GOOSE! Do you know this game? That’s how I’m feeling with oestrogen – high-high-high-LOW!-of late. Likely similar to your experience, the majority of my female clients battle with oestrogen dominance, therefore I get so used to looking for it, expecting it: the high Cu, the profoundly elevated SHBG, maybe a raised ESR. So much so that sometimes the low ones can catch you out, especially of course when it happens in women way way before menopause.
We’re so resolved to hear bad press about oestrogen and to be armed ready to saturate our patients with broccoli extracts of the highest order – do we remember the clinical features and markers of an oestrogen deficit and know what to do with those women who simply don’t have enough? (more…)
During mentoring sessions over the last week I’ve been prompted to ask a few practitioners if their patient had any signs, either clinically or in their pathology results, of high oestrogen. Each time it kind of caught the practitioner off guard because their patients weren’t presenting with conditions overtly related to an oestrogen excess and they hadn’t specifically ‘tested’ for this. However, in each instance the information was already there in the case, it was just a matter of knowing what markers to look for.
So some patients scream ‘high oestrogen’ right from the minute they enter the room? But often others present with health problems that don’t necessarily appear related at first glance. Regardless, their condition absolutely could be being compounded by this background imbalance – think thyroid & other autoimmune conditions for example.
There are plenty of patients who don’t have the exaggerated clinical presentation but still have this imbalance as a significant compounder or perpetuating issue in terms of their pathology.
Relax – I am not suggesting salivary hormones or any form of expensive testing all round (!) – in fact what I am saying is before you even consider yet another pay out of pocket test, costing your patient more time and money, we should look to the clues that are already there, in standard blood tests. Amazingly, you can infer a lot not just about the overall oestrogenic load but also pick up some clues as well about where the excess might be coming from.
In this Update Rachel brings together her 10 quick tips on how to recognise either high oestrogen and/or the potential underpinning reason behind the excess, in a range of easily accessible markers. A great refresher and synthesis of ideas on this important aspect of diagnosis and clinical management. This Update in Under 30 is now available to purchase as a download, click here to find out more or if you’re interested in a 12mo subscription click here