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CASE STUDY
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Depression, Metabolic Syndrome & Methylation Dysfunction — A Functional Medicine Recovery Story​​​
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Who This Is For?

If you have been struggling with unstable mood, crushing fatigue, metabolic problems, poor gut health, and a sense that your body and mind are simply not working the way they should — for months or years, and feel like nothing has worked — this case study is for you.

This is the story of how W.E., a man in his fifties, found meaningful, lasting improvement through a root-cause functional medicine approach — after years of managing his symptoms without ever fully addressing why they were happening.

If you are looking for functional medicine support for mood disorder, a nutritional therapist for metabolic syndrome, or a root-cause approach to mood dysregulation, methylation dysfunction, or gut-immune issues in Ireland, the UK, or online — read on.

The Journey

Presenting Symptoms & Goals

W.E. came to Paul having lived with a complex constellation of health challenges for many years, including:​ 

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•    Severe mood swings — significant instability managed with multiple psychiatric medications.

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• Metabolic syndrome — elevated fasting glucose at 9.0 mmol/L (strongly suggestive of impaired glucose tolerance), raised triglycerides, LDL cholesterol and total cholesterol

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•    Hormonal insufficiency — low free testosterone (0.141 nmol/L) and low total testosterone (8.46 nmol/L), impacting energy, mood and physical vitality

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•     Impaired kidney function — reduced eGFR of 75 mL/min/1.73m² and mildly elevated urea

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•    Gut dysfunction — compromised digestive enzyme output (Elastase-1 194 µg/g, below the 200 µg/g threshold), elevated fat malabsorption (Steatocrit 20H), and a significantly dysregulated immune response in the gut (Secretory IgA 3081 µg/g, far above the reference ceiling of 2010)

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•    Microbiome imbalance — depleted Roseburia, low Bacteroidetes and Firmicutes phyla counts, and a Firmicutes:Bacteroidetes ratio of 0.15, indicating a profoundly disrupted gut ecosystem

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•    Methylation dysfunction — genetically compromised methylation capacity (heterozygous MTHFR C677T and A1298C, homozygous MTRR A66G) with markers showing a depressed SAM/SAH ratio and a system tilted toward un-methylated metabolites

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•    Adrenal exhaustion and mineral dysregulation — hair mineral analysis showing a classic burnout pattern: calcium ‘shell’, severely depleted sodium and potassium, and extreme calcium-to-potassium and calcium-to-sodium ratios

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•     Possible autoimmune activity — a history suggesting lichen planus and sarcoidosis, along with Wheat Zoomer findings showing elevated antibodies and a raised beta-endorphin signal indicative of leaky gut

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•     Kryptopyrroles in urine at 140.2 ng/mL — upper normal range but clinically significant given the constellation of symptoms, including pyroluria-associated mood instability, stress sensitivity and nutrient depletion

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•  Aching bones in the morning, poor sleep, and a pervasive difficulty maintaining loving connection and emotional security•   

W.E. was not simply looking for symptom relief. He wanted to understand the biological roots of his experience — and to reclaim a life with stable energy, clearer mood, and genuine wellbeing.

Background

W.E. had been navigating a profoundly demanding health journey for over two decades. A significant period of chronic stress and emotional strain — including a history of significant psychosocial stressors from early life — had placed a sustained load on his nervous system and HPA (hypothalamic-pituitary-adrenal) axis over many years. 

Conventional medicine had provided essential stabilisation through psychiatric medication, but the root-cause drivers — metabolic dysfunction, gut-immune disruption, methylation compromise, and adrenal dysregulation — remained unaddressed. W.E. came to Paul seeking a more complete picture and a strategy that worked with his biochemistry, not just around it.

Key Testing & Clinical Insights

Rather than addressing symptoms in isolation, a comprehensive functional medicine assessment was carried out at the start of the programme to identify the underlying drivers.

 

 

 

 

 

 

 

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All clinical test results from W.E.’s initial functional medicine assessment. Each panel is labelled — see full findings below.

Initial Blood Panel — Metabolic, Cardiovascular & Thyroid

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WE — Case Study: What the Tests Revealed

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Initial Blood Panel

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The initial blood panel told a clear story of a body under significant metabolic strain. Fasting glucose and insulin were both elevated — a pattern that points firmly toward insulin resistance, where the body is working harder and harder to manage blood sugar but losing the battle. Alongside this, cholesterol and triglycerides were raised, completing a picture that functional medicine recognises as metabolic syndrome — a cluster of findings that meaningfully increases cardiovascular risk if left unaddressed.

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The kidneys were showing early signs of strain, and elevated urea suggested the body had been under chronic stress for some time. Thyroid peroxidase antibodies came back significantly raised — a clear signal that the immune system was attacking the thyroid. This autoimmune activity, sitting alongside W.E.'s history of lichen planus and other immune-related conditions, confirmed that immune dysregulation was a central thread running through the whole picture.

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Comprehensive Stool Analysis

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The gut results were some of the most striking in the entire panel. Pancreatic enzyme output was compromised, meaning W.E. was not fully breaking down and absorbing dietary fats — something that has far-reaching effects on energy, hormones, and brain function.

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Most significant was the gut immune marker Secretory IgA, which came back dramatically elevated. This is the frontline immune protein of the gut lining, and levels this high indicate a gut immune system in a sustained state of high alert — typically driven by chronic infection, food reactivity, or intestinal permeability. A further marker associated with hormonal disruption and toxin recirculation in the colon was also raised. Taken together, the gut was inflamed, overworked, and struggling — a pattern consistent with W.E.'s fatigue, mood instability, and broader systemic symptoms.

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Microbiome Profile

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The gut microbiome analysis revealed a significantly depleted ecosystem. Several keystone bacterial species — the ones responsible for producing butyrate, the primary fuel for the gut lining — were low. The two dominant bacterial families that make up the bulk of a healthy gut were both suppressed well below their expected ranges.

 

This matters well beyond digestion. The gut microbiome plays a direct role in mood regulation through the gut-brain axis, in immune system calibration, and in the production of key nutrients. A microbiome this disrupted creates a cascade of downstream consequences that can show up as fatigue, low mood, brain fog, and immune dysfunction — all of which were present in W.E.'s case.

 

Hair Mineral Analysis (HTMA)

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The hair mineral analysis painted a vivid picture of chronic stress physiology and adrenal exhaustion. Calcium was extremely elevated — a pattern seen when the body has been under prolonged stress and calcium migrates out of cells and into soft tissue. Meanwhile, sodium and potassium — the minerals most directly linked to adrenal function — were severely depleted.

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The relationship between these minerals told the most important story: the ratios were so far outside optimal ranges that they pointed toward profound adrenal insufficiency and sluggish thyroid function. Copper was elevated, which has direct implications for mood and oestrogen metabolism. Selenium — critical for thyroid hormone conversion and antioxidant defence — was borderline low. Several toxic metals were present within reference range but at levels worth monitoring given the overall picture.

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Methylation Status & Genetic Polymorphisms

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The methylation panel revealed a system under significant compromise. W.E. carried genetic variants in key enzymes responsible for converting folate and recycling B12 into their active, usable forms. These aren't rare findings, but when several variants occur together — as they did here — their combined effect substantially reduces the body's capacity to run the methylation cycle efficiently.

 

Methylation underpins an extraordinary range of functions: neurotransmitter production, mood regulation, DNA repair, detoxification, and immune response. The functional markers confirmed the genetic picture — the system was measurably tilted away from optimal methylation, with insufficient methyl groups available for all the processes that depend on them. In a person presenting with mood instability, fatigue, and cognitive symptoms, this was a significant and actionable finding.

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Kryptopyrroles — Pyroluria Screen

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Kryptopyrroles in urine came back at the upper end of the reference range — technically within limits, but clinically meaningful given W.E.'s presentation. In functional medicine, elevated kryptopyrroles are considered significant when they occur alongside a characteristic symptom profile: mood instability, stress sensitivity, difficulty tolerating pressure, and a family history of mental health challenges. W.E. met several of these criteria.

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The reason this matters is that elevated kryptopyrroles deplete zinc and vitamin B6 — two nutrients that are essential for making neurotransmitters. Without adequate levels of both, the brain's chemistry is working at a disadvantage. This finding added another layer of explanation to W.E.'s mood and nervous system symptoms, and pointed directly toward a targeted nutritional intervention.

The Programme

Based on the findings, a fully personalised programme was designed — not a template, but a strategy built specifically around W.E.’s biochemistry, history, and goals.

Nutrition Strategy

The dietary foundation was a gradual transition toward an animal-based, low-carbohydrate approach — beginning with a carnivore diet startup and moving progressively toward the Paleolithic Ketogenic Diet (PKD) framework. The goal here was multifaceted: to reduce the antigenic load driving gut inflammation and autoimmune activity (particularly relevant given the Wheat Zoomer findings and leaky gut markers), to restore insulin sensitivity by removing dietary carbohydrates that were chronically elevating glucose and insulin, and to provide a nutrient-dense substrate of bioavailable animal protein, organ meats, and healthy fats to support hormonal recovery and methylation.

Goat kefir was introduced to support the gut microbiome alongside the dietary transition. A ProLon 5-day fasting-mimicking diet protocol was incorporated periodically to drive autophagy, reduce visceral fat, and support metabolic reset — a clinically appropriate tool given the metabolic syndrome picture. Bulletproof coffee and bone broth were included as practical, nourishing anchors to the daily routine. The dietary approach was intentionally simple: remove the foods driving inflammation and dysregulation, and provide the raw materials the body needed to repair.

Supplement & Detox Protocol

Methylation & Nervous System Support

Goal: Address the MTHFR and MTRR variants and restore methylation capacity. Approach: B-Minus (B12 and folate-free B-complex from Seeking Health) to provide B vitamins without adding unmethylated forms that could be problematic given the SNP profile; progressive introduction of methylated B12 (methylcobalamin) and methylfolate as the system stabilised. MegaMag and calcium-magnesium combination to address the severe mineral deficiencies identified on HTMA, particularly relevant given the adrenal burnout picture and high Ca:Mg ratio.

Gut Repair & Microbiome Restoration

Goal: Restore intestinal integrity, reduce immune activation, and repopulate the microbiome. Approach: MegaSporeBiotic (spore-based probiotic from Microbiome Labs) introduced on a careful titration schedule — beginning at one capsule every second day and building gradually to two daily — to recondition the gut and promote microbial diversity. Bio.Me Mind + Mood (Invivo) for gut-brain axis support. The dietary changes themselves were central to this goal, removing the gluten and leaky-gut drivers identified by the Wheat Zoomer.

Hormonal & Metabolic Recovery

Goal: Support testosterone recovery, address insulin resistance, and restore metabolic function. Approach: Alpha Male Ultimate Blend for natural testosterone support; high-dose omega-3 (Ultimate Omega, Nordic Naturals, 15ml daily for adults) to support lipid profile, inflammation reduction and hormonal production; Piping Rock ADK (Vitamins A, D3 5000IU, K2) as a high-strength vitamin D complex to support immune regulation and hormonal pathways; chromium three times daily to help stabilise blood sugar dips during dietary transition.

Electrolyte & Adrenal Support

Goal: Replenish the severely depleted sodium, potassium and mineral profile identified on HTMA. Approach: Optimal Electrolyte (plain, Seeking Health) — two scoops daily — as the primary electrolyte foundation, particularly important during the low-carbohydrate dietary transition when electrolyte losses increase.

Lifestyle & Nervous System Support

The nervous system work was not an afterthought — it was clinically integral. Buteyko breathing practice was introduced for its established benefits in sleep apnoea, histamine regulation, and autonomic nervous system balance; W.E. was directed to 1 hour of practice daily, with sessions structured in blocks of 15–20 minutes. Somatic breathwork classes were added to complement this work.

A structured nervous system retraining protocol based on polyvagal theory, vagus nerve toning, and somatic movement was recommended to address the deep pattern of nervous system dysregulation underpinning the mood instability.

 

Joe Dispenza’s meditation and neuroplasticity work was introduced as a daily practice — at minimum one 3-minute meditation daily, with a commitment to watch one testimonial video daily to build understanding of and belief in the process.

Weight-bearing exercise was introduced through a structured 3-day Push/Pull/Legs resistance programme, building progressively from 50–60% of maximum effort. Cold showers were incorporated as a daily autonomic nervous system stimulus. Sleep hygiene was prioritised throughout.

Every element of the programme was reviewed and adapted at each consultation — nothing was set-and-forget.

Results

The transformation in W.E.’s key biomarkers across the programme was, in clinical terms, remarkable.
MSQ score at initial consultation: 40 (Jan 25: 53 | Feb 25: 33 | Mar 25: 32 | Apr 25: 12 | Jun 25: 13 | Oct 25: 10)
The MSQ scores tell a story of genuine, progressive transformation — not a straight line, but the kind of arc that reflects real biological healing: an initial increase as the programme began to stir up the system, followed by a steady and sustained fall, culminating in a score of 10 by October 2025. A score of 10 from a starting point of 40 represents an extraordinary reduction in overall symptom burden.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

In the early weeks, the priority was metabolic stabilisation. The transition to a low-carbohydrate, animal-based diet initially required adjustment — the body adapting from glucose-dependency to fat-based metabolism — but the electrolyte support and supplement framework helped ease this process.

 

At the same time, the gut protocol began its work: MegaSporeBiotic was titrated carefully to avoid excessive detoxification symptoms, and the removal of gluten and inflammatory foods reduced the chronic antigen load that had been driving the elevated Secretory IgA and gut immune activation.

Through the middle phase, the data began to shift. Testosterone was recovering. Glucose and insulin were coming under control — the combination of dietary carbohydrate restriction and improved gut-liver-adrenal axis function allowing insulin sensitivity to restore. MSQ scores, which had briefly risen in January (a common pattern as the body adjusts), began to fall meaningfully: from 53 in January 2025 to 33 in February, 32 in March, and then a significant drop to 12 in April.

By October 2025, W.E.’s MSQ score had reached 10 — a profound reduction from the 40 he had recorded at the start. The methylation support, the nervous system retraining, and the progressive lifestyle interventions had combined to shift not just individual markers but the overall state of his physiology. He noted improvement in mood stability coinciding with increased meat consumption and the reinstatement of lamotrigine to a working dose — a reminder that in complex cases like this, functional medicine and conventional medical management work best in collaboration.

Summary of Results

•    MSQ score reduced from 40 at intake to 10 by October 2025 — a 75% reduction in overall symptom burden
•    Fasting glucose normalised from 9.0 to 4.9 mmol/L — insulin resistance substantially improved
•    Insulin reduced from 208 to 20 pmol/L — a tenfold improvement in hyperinsulinaemia
•    Triglycerides normalised from 2.3 to 0.9 mmol/L; LDL and total cholesterol both improved
•    Total testosterone doubled from 8.46 to 15.3 nmol/L; free testosterone improved from 0.141 to 0.263 nmol/L
•    Kidney function restored: eGFR improved from 75 to >90; urea normalised
•    Acid-base balance restored: bicarbonate normalised from 19.4 to 24.5 mmol/L
•    Intracellular magnesium normalised; adrenal and nervous system function progressively supported
•    Mood stability improved in correlation with dietary intervention and programme adherence

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Recognise yourself in this story?

If you’ve been struggling with similar symptoms and haven’t found answers, a functional medicine assessment could be the turning point.

 

 

 

Why This Worked

The root cause was identified, not suppressed. W.E. had been managing bipolar disorder with medication for years — essential care, but not the complete picture. Comprehensive functional testing at intake revealed a system under extraordinary metabolic, immunological, and neurological strain. Insulin resistance, gut immune activation, adrenal burnout, and methylation compromise were all contributing to the load his nervous system was carrying. Addressing these drivers — not just the symptoms — was what made the difference.

The gut was central, not peripheral. A Secretory IgA of 3081 µg/g, a depleted microbiome, and Wheat Zoomer evidence of intestinal permeability told a clear story: this client’s gut was in a state of chronic immune activation. The gut-brain axis is not a metaphor — it is a direct biological pathway. Restoring gut integrity and microbial diversity was a core pillar of the mood and nervous system recovery, not an add-on.

Genetics informed the strategy but did not determine the outcome. The MTHFR and MTRR variants meant that standard B-vitamin supplementation could have been counterproductive. Understanding the specific SNP profile allowed the supplement protocol to be carefully designed around W.E.’s actual biochemistry — supporting methylation without overwhelming a compromised system.
The nervous system was addressed as biology, not just behaviour. Buteyko breathing, somatic bodywork, and the nervous system retraining programme were not lifestyle suggestions — they were clinical interventions targeting the autonomic nervous system dysregulation that underpinned so much of W.E.’s presentation. Combined with Joe Dispenza’s meditation work, this aspect of the programme helped shift the fundamental physiological state from which everything else was operating.

The programme evolved as W.E. did. When heart arrhythmia symptoms appeared mid-programme, Paul adapted immediately — removing all supplements temporarily to identify the trigger, then reintroducing one at a time. When mood dipped in October, the interaction between lamotrigine dosing and dietary protein intake was explored, and the protocol was adjusted accordingly. This is functional medicine as it is meant to be practised: responsive, precise, and built on a genuine therapeutic partnership.

Know someone who needs to read this?​​​

If this sounds like someone you care about, share it — it might point them in the right direction.

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About Paul Foley

Paul Foley is one of the leading nutritional therapists and functional medicine practitioners working across the UK and Ireland, specialising in autoimmune conditions, chronic fatigue syndrome, ME/CFS, mould and mycotoxin toxicity, gut-immune dysfunction, SIBO, hormonal imbalance, mental health, and nervous-system dysregulation.

His work integrates evidence-based functional testing with personalised nutrition and systems-level recovery strategies, supporting clients who have often “tried everything” without lasting results.

Paul works with clients in Dublin, London, and remotely worldwide. If you are searching for the best functional medicine practitioner or nutritional therapist for bipolar disorder, metabolic syndrome, gut health, hormonal issues, methylation dysfunction, or complex unexplained symptoms — Paul’s approach may be the missing piece.

Ready to find your root cause?

Paul works with clients across Ireland, the UK, and worldwide via remote consultation.

 

Frequently Asked Questions

Can functional medicine help with Depression disorder?

Depression disorder is complex and multifactorial — and for many people, the biological drivers behind mood instability go well beyond neurotransmitter imbalance alone. Functional medicine doesn’t replace psychiatric care, but it works alongside it, identifying root-cause contributors such as methylation dysfunction, gut-immune dysregulation, blood sugar instability, nutrient deficiencies, and nervous system dysregulation that can all amplify mood swings and reduce resilience. Paul’s approach involves comprehensive testing at the outset to understand each client’s unique biology, and building a personalised programme around what the tests actually show.

What causes metabolic syndrome, and can it be improved without medication?

Metabolic syndrome is a cluster of conditions — elevated blood glucose, insulin resistance, high triglycerides, low HDL, and central obesity — that together significantly increase the risk of type 2 diabetes and cardiovascular disease. The root causes are typically a combination of chronic carbohydrate excess, gut dysfunction, hormonal imbalance, and chronic stress. For many people, a personalised nutritional strategy — particularly a low-carbohydrate or animal-based approach — can produce significant improvements in metabolic markers. In W.E.’s case, fasting glucose normalised from 9.0 to 4.9 mmol/L and insulin dropped from 208 to 20 pmol/L through dietary and lifestyle intervention alone, without medication changes to address these markers.

What is methylation dysfunction, and why does it matter for mood and health?

Methylation is a fundamental biochemical process that happens billions of times per second in every cell of the body — it’s involved in producing neurotransmitters like serotonin and dopamine, regulating gene expression, supporting detoxification, and building and repairing DNA. When methylation is compromised — whether due to genetic variants like MTHFR, nutrient deficiencies, or chronic stress — the downstream effects can include mood dysregulation, fatigue, hormonal imbalance, immune dysfunction, and increased vulnerability to toxic load. Identifying and supporting methylation is a core part of Paul’s functional medicine approach, and requires careful, individualised assessment rather than a one-size-fits-all supplement protocol.