Depression, metabolic syndrome &
methylation dysfunction resolved

Presentation & Background

S.F., a man in his fifties, had lived with a complex constellation of health challenges for 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. He came to Paul seeking a more complete picture and a strategy that worked with his biochemistry, not just around it.

Presenting Conditions

• Severe mood instability managed with multiple psychiatric medications
• Metabolic syndrome — fasting glucose 9.0 mmol/L, elevated triglycerides and cholesterol
• Low testosterone — 8.46 nmol/L total, impacting energy, mood and physical vitality
• Gut dysfunction — compromised enzyme output, fat malabsorption, severely elevated Secretory IgA
• Profound microbiome disruption — depleted keystone bacteria
• Methylation dysfunction — MTHFR C677T and A1298C, MTRR A66G genetic variants
• Adrenal exhaustion — HTMA showing classic burnout pattern, depleted sodium and potassium
• Elevated kryptopyrroles — depleting zinc and B6, driving mood instability
• Possible autoimmune activity — lichen planus, sarcoidosis history, leaky gut markers

Root-Cause Findings

Rather than addressing symptoms in isolation, a comprehensive functional medicine assessment was carried out across multiple systems simultaneously — producing a picture that explained why years of medication alone had not resolved the underlying drivers.

• Blood panel: Insulin resistance confirmed — fasting glucose 9.0 mmol/L, insulin 208 pmol/L. Metabolic syndrome pattern with elevated cardiovascular risk markers. Thyroid peroxidase antibodies raised — autoimmune activity confirmed.
• Gut analysis: Pancreatic enzyme output compromised. Secretory IgA 3081 µg/g (far above reference of 2010) — gut immune system in a state of sustained high alert. Gut-brain axis severely disrupted.
• Microbiome: Keystone bacteria depleted. Firmicutes:Bacteroidetes ratio of 0.15 — profoundly disrupted ecosystem with direct consequences for mood, energy and immune function.
• Hair mineral analysis: Classic adrenal burnout pattern. Extreme calcium-to-potassium and calcium-to-sodium ratios. Elevated copper — direct implications for mood and hormone metabolism.
• Methylation panel: Multiple genetic variants compromising the methylation cycle. Insufficient methyl groups for neurotransmitter production, DNA repair, detoxification and immune function.

The Programme

Nutrition Strategy

A gradual transition toward an animal-based, low-carbohydrate framework — beginning with a carnivore startup and moving toward the Paleolithic Ketogenic Diet. The goal: reduce the antigenic load driving gut inflammation and autoimmune activity, restore insulin sensitivity by removing dietary carbohydrates, and provide nutrient-dense animal protein and organ meats to support hormonal recovery and methylation. ProLon 5-day fasting-mimicking protocols were incorporated periodically to drive autophagy and metabolic reset.

Supplement Protocol

• Methylation support — B-Minus complex (avoiding unmethylated forms given the SNP profile), progressive introduction of methylated B12 and methylfolate
• Mineral repletion — MegaMag and calcium-magnesium for the severe HTMA deficiencies
• Gut restoration — MegaSporeBiotic carefully titrated, Bio.Me Mind + Mood for gut-brain axis support
• Hormonal recovery — Alpha Male blend, high-dose omega-3, ADK complex, chromium for blood sugar stability
• Electrolyte repletion — Optimal Electrolyte, two scoops daily, especially important during low-carb transition

Nervous System & Lifestyle

Buteyko breathing (1 hour daily), somatic breathwork, polyvagal nervous system retraining, Joe Dispenza meditation practice, weight-bearing resistance training (Push/Pull/Legs, 3 days per week), and cold showers were all integrated as clinically necessary interventions — not lifestyle suggestions.

Why This Worked

The gut was central, not peripheral. A Secretory IgA of 3081 µg/g, a depleted microbiome, and leaky gut markers told a clear story — this client's gut was driving the mood instability, energy failure and immune dysregulation through the gut-brain axis. Genetics informed the strategy but did not determine the outcome — understanding the specific SNP profile allowed the B-vitamin protocol to be designed around his actual biochemistry rather than making it worse. And the nervous system was addressed as biology, not just behaviour: Buteyko breathing and somatic work were targeting the autonomic dysregulation that underpinned everything else.