Case Study: Robert
Background / Details
Robert recalled no health issues as a child or teenager, and had been extremely active during school (football, martial arts and weightlifting).
During his A level exams, a time that he was staying up late to revise and also working part-time, he suffered a ‘crash’. He managed to get through his exams but, from this point on, struggled with fatigue, concentration, mood. He could no longer take part in his athletic activities, other than a reduced-volume weights session once per week, which was a huge blow (as this played a major role in channelling stress and involved a major social outlet).
He had trialled a decent number of supplements based on internet research. Most had done little, but he had found a benefit in most calming herbs and B6. These allowed him to get reasonable sleep but he still remained very tired.
Alongside the fatigue and other symptoms, it was notable that he had cold hands/feet alongside reduced hair growth (a set of symptoms often associated with hypothyroidism) and he was consuming 3,700 kcals per day in order to maintain weight. He also had a number of symptoms associated with reduced cortisol activity (getting wired from coffee, feeling weak if not eating regularly, big energy dip in the afternoon, energy dip every afternoon, slow to wake up in the morning and slow to switch off at night).
Robert took the Organic Acids Test ahead of our initial appointment. This showed:
- Low Aconitic Acid (a sign of mitochondrial hypoxia)
- Raised malic acid (associated with cellular hypothyroidism)
- Markers associated with low serotonin and low noradrenaline (slow conversion from dopamine)
- Low B6, Low Folate, Low B12
- Raised oxidative stress
- Markers for dysbiosis (bacteria, including clostridium markers)
He had otherwise been given based blood tests at his doctor (all were in range, with the exception of raised cholesterol) and some additional blood testing (iron was within range but serum levels of B12 were raised). He had also had some thyroid testing which, despite the thyroid-associated symptoms above, showed no markers out of range (although this only tested TSH and T4, which can be highly unreliable).
Points for Consideration
Note: blood levels of B12 can rise if transport of B12 into cells is disturbed. This transport is conducted by a protein called transcobalamin, which is adversely affected when there is excessive glycation (which calls for consideration of blood sugar levels and oxidative stress). Picking up such patterns are important because, in these scenarios, providing huge doses of supplementary B12 are unlikely to do much at cellular level, which is where B12 is active.
The raised Malic Acid is a highly relevant marker, as it not points to problems with the thyroid transport proteins (that move thyroid hormones into the cells), but also provides an explanation for this type of scenario; one where the symptoms of hypothyroidism are present yet the blood levels look OK.
Initial Recommendations / Removing Obstacles
At first, we focused on removing the most ‘obvious’ obstacles. I identified these to be the mitochondrial hypoxia, correcting nutrient shortages and supporting neurotransmitter balance.
The mitochondrial hypoxia can easily be caused by anaemia, and this was an obvious consideration given the low folate/B12 status (although iron had already been ruled out). Endotoxemia was also a consideration (given that this is a very common cause of hypoxia, and ties in with the adrenal picture we outlined above).
B6 was still short, despite Robert already taking this. B6 is depleted by stress, and so I wanted to compensate with an increased dose. B6 is vital for the formation of both dopamine and serotonin. Folate is also crucial for methylation, a chemical process that supports 600 different reactions across the body (and especially important for detoxification, immune function and hormonal balance and neurotransmitter support: most affected here are dopamine and serotonin).
There are a lot of options when it comes to supporting serotonin but this can be easily limited if there are any issues with folate status or cortisol signalling.
For the above reasons, it was clear that Robert had no chance at maintaining optimal serotonin signalling while methylation, cortisol signalling and B6 status were still compromised. Equally, all areas of the body (especially energy-intensive areas, such as the brain) may be affected when mitochondrial activity is sub-par, while I expected a lack of adrenal support would make overactivity of the stress response (with subsequent increase in adrenaline, gut permeability and endotoxemia) inevitable. Therefore, the plan centred on removing these obstacles (and all their downstream disturbances on multiple areas of the metabolism) and then see what areas responded and which areas still needed attention.
Histidine to aid cellular transport of B12 – the transport is supported by carnosine, which histidine converts into, although I chose histidine over carnosine because histidine also supports exercise tolerance through modulating pH at muscle cells.
Folate – introduced slowly to avoid unnecessary ‘start-up’ reactions. Via the formation of BH4, folate contributes to the healthy formation of serotonin and dopamine.
Licorice Root – to support cortisol signalling and serotonin trafficking (the serotonin autoreceptor can limit the activity of serotonin, and it is highly under-discussed the role of cortisol receptors in maintaining healthy regulation of these autoreceptors).
Introduction of liver – a rich source of copper (and also of Vitamin A, necessary to ensure healthy production of ceruloplasmin, needed to escort copper). Copper is crucial for the activity of dopamine-beta-hydroxylase, which converts dopamine into noradrenaline.
Introduction of turkey tail mushrooms – there are many benefits to this, although the primary aim was to limit any undesirable activity of clostridia bacteria (as these can produce a metabolite that interferes with the activity of the dopamine-beta-hydroxylase enzyme).
Swedish Bitters and Betaine HCL – to support digestive absorption and conditions in the digestive tract.
Big improvement in clarity / mental stamina. These are functions associated with health noradrenaline signalling, and so I expect that both the support of copper status (in the form of liver) and limiting formation of clostridia metabolites helped. The neuroplasticity effects of serotonin should not be overlooked as a contributing factor.
‘Good tired’. Robert noticed this quickly after introducing Licorice, with deeper sleep and improved mood. This is something I regularly see when someone with high adrenaline levels (something that tends to make them ‘tired but wired’) is given effective cortisol support. As much as cortisol is often considered in a negative light, it is actually a hugely beneficial hormone (especially in the way that it provides negative feedback to the hypothalamus, which actually switches off the stress response).
No longer needed such high calorific intake. This was the hope for the digestive support, although I was also expect the effect of Licorice (it’s cortisol effects are highly anti-adrenaline, and therefore have major effects on the catabolic/energy-wasting effects of adrenaline).
Alongside this, HRV values showed a substantial improvement (starting in the 20s, and trending in the 40s after a couple of rounds). Overall, we were pleased with Robert’s early response. Most ‘symptoms’ were now gone but there was still some way to go (much more able to do things but still no bounce’ and still a lack of tolerance for exercise).
Secondary Steps / Further Customization
We repeated the Organic Acids test. Cellular B12 was now in range, with cellular hypoxia still present (although improved). Folate and B6 status now in a good place. Serotonin and noradrenaline status now in a good place. Malic acid, the marker for cellular hypothyroidism, and markers for oxidative stress was still raised. Dysbiosis was still present, but it was clear to me (via reports energy and HRV values) that there were still not sufficient resources to undertake successful anti-microbial steps. I suspected that there was still overactivation of the stress response (which results in further opening of the gut lining, and further endotoxemia, which drives hypoxia due to the excess nitric oxide that is produced in response). As long as there are some mitochondrial issues, I would not yet expect any individuals to feel back to where they want to be.
Because the hypothyroid symptoms were still here, I ran a thyroid test as I wanted to see if there was any change from before (and also to complete the picture, given that his prior test had only included TSH and T4). It was a very useful test, as it allowed us to hone in on our target: thyroid transport into cells. It did do because it showed blood T3 levels that were towards the higher end of the range (5.4 nmol/L) and T4 levels at bottom of the normal range. This picture, combined with hypothyroid-associated symptoms and hypothyroid-associated markers (raised cholesterol and malic acid), is a huge clue that cellular transport is not happening the way it should (the cellular transport for T4 is disproportionately affected, which helps explain the results from the thyroid panel). And yes, cholesterol was still raised.
When it comes in inhibitors of cellular transports, we are left with a list of usual suspects, although the results and case history framed increased intestinal permeability, ongoing hypoxia issues and likely insulin sensitivity challenges as the most likely suspects.
With intestinal permeability in mind, we considered the potential role of postural set-up, giving consideration to the higher-than-normal likelihood of hits Robert had taken during his years of martial arts (and the falls that came with it) and also the way posture can impact on intestinal tension (which is not only a hugely under-discussed pattern, but can also promote fermentation, and therefore subsequent increases in intestinal permeability and therefore endotoxemia). I therefore recommended some postural support and some techniques to reduce tension (combination of chiropractic and TRE/Tension Release Exercises).
We also considered how cortisol signalling may fit into this, as any lingering endotoxemia (flagged by the hypoxia patterns that were still remaining and some symptomology) is well-known to impact on sensitivity of cortisol receptors, which means other steps to support cortisol may be limited. I therefore made recommendations to add Korean Ginseng, which improves cortisol sensitivity.
What stood out as the most obvious obstacle separating Robert from his aims was the hypothyroid-type picture. The symptoms and raised Malic acid painted a picture, and we considered the likelihood of insulin resistance as a legacy of his prior problems (this is common whenever there is hypoxia, as there is insufficient oxygen to burn the energy compounds, and thus the mitochondria are forced into slowing energy usage, and therefore limiting energy uptake as a consequence). This would not be the only factor, of course, with inflammatory activity from dysbiosis and any lingering issues with cortisol sensitivity still relevant. To establish the role of insulin sensitivity, we ordered additional blood tests (which showed raised cholesterol, low HDL, exactly in line with insulin resistance) and a fatty acids profile (which tied in with this and also identified a call for an anti-inflammatory fatty acid DGLA).
Korean Ginseng was particularly helpful, even though it made it very difficult to get to sleep on the first few nights
TRE and chiropractic were hit and miss for a while, with some signs that both were doing something although mainly in revealing pockets of previously-unnoticed tension, at which point Robert experienced a big release in TRE. This not only saw his sleep quality and energy improve in the aftermath, but also made him more ‘adjustable’ when at the chiropractor.
This is the point where Robert described himself as ‘fixed’, and it was also the time he stopped feeling sensitive to the cold. Shortly after, his hair became thicker. However, there was still one thing that we were yet to attend to: microbial balance of the gut. Now that Robert’s energy and resilience were robust, we ran a stool test before applying the appropriate anti-microbial/probiotic support (and he reported an extra ‘spring in his step’ after this course was undertaken).
HRV values settled in the mid-60s following these changes, and I felt that these responses made him a good candidate for the insulin sensitizing steps. We made use of Berberine, Apple Cider Vinegar and Chaga, while limiting carbohydrates to 140g/day (apart from training days). He felt some benefits from the start of this phase, although there was an ongoing (but potent) shift over the course of the eight weeks that followed, which took Robert into territory that he described as well above his prior baseline and the healthiest he had ever felt.