The ScienceBehind HRU
Built on decades of established physiological research and validated measurement technologies.
The Challenge
Why HRU Exists: From Medically Unexplained Symptoms (MUS)to Measurable Data
In every healthcare system there is a growing group of people who feel unwell, yet standard tests come back "normal". Their symptoms are real — fatigue, non-specific pain, gut discomfort, palpitations, poor sleep — but don't fit neatly into a disease box.
HRU is designed to sit exactly in that gap
To objectively map the physiological terrain behind the "body whispers": the early, subclinical changes in stress axis, fluid distribution, matrix congestion and cellular efficiency that often precede overt disease.
What large MUS studies and expert guidance agree on:
- These patients are not "imagining it"
- Their symptoms often sit at the intersection of chronic stress, low-grade inflammation, altered body composition, and autonomic dysregulation
- These processes are measurable, but not captured by routine blood work or imaging
Global Research Data
MUS Prevalence: A Growing Global Concern
Global research reveals concerning trends in medically unexplained symptoms across a massive international sample of over 1.2 million participants.*
Year-over-Year MUS Prevalence
Percentage of subjects with MUS presence
Gender Distribution
Most Common Symptoms
Most prevalent medically unexplained symptoms
Consistent Prevalence
MUS affects approximately two-thirds of the population consistently across years, highlighting the need for better diagnostic approaches.
Systemic Patterns
Symptoms cluster across autonomic, digestive, and mood systems — suggesting interconnected physiological dysfunction that standard tests miss.
The Integration
How HRU Reads the "Body Whispers"
We use four peer-reviewed technologies to objectively map the physiological terrain behind your symptoms
What NeuroFlow measures
NeuroFlow uses photoplethysmography (PPG) sensors on the fingers to record pulse waveforms and derive heart rate variability (HRV) – millisecond changes in the time between beats that reflect the balance between sympathetic ("fight/flight") and parasympathetic ("rest/recover") activity.
- Modern work shows that high-quality PPG HRV is comparable to ECG HRV for both short- and long-term recordings
- PPG has become an accepted method for non-invasive autonomic assessment
- Includes sympathetic activation during stress tests
Why HRV matters
HRV is where "stress" stops being an opinion and becomes a measurable biological load.
- HRV is an established marker of autonomic function recognised by the ESC/Task Force as a powerful index of cardiovascular and neuro-autonomic health
- Lower HRV predicts higher cardiovascular and all-cause mortality and is consistently associated with chronic stress, anxiety, depression, PTSD and other stress-related conditions
- HRV is tightly linked to inflammation, adiposity and cardiometabolic risk – lower HRV tracks with higher inflammatory markers and lipid accumulation
How NeuroFlow is used in HRU
We use rest and challenge protocols to create a quantitative map of autonomic strain.
- Rest and challenge protocols allow us to see how quickly the system recovers after stress – a key element of allostatic (adaptive) capacity
- We interpret classic time- and frequency-domain HRV metrics (e.g. SDNN, RMSSD, HF, LF/HF) in the context of symptoms, sleep, and MUS, rather than in isolation
- The result is a quantitative map of autonomic strain, showing whether complaints like fatigue, palpitations, brain fog or poor sleep are accompanied by a measurable loss of autonomic flexibility
What NeuroFocus measures
NeuroFocus is based on hemoencephalography (HEG) – an optical method, placed over the forehead, that tracks changes in blood-flow and oxygenation in the prefrontal cortex (PFC) during simple tasks.
- The PFC is central to executive function, emotional regulation and inhibitory control
- Neurovisceral models show that PFC activity and HRV are tightly linked
- When the PFC cannot regulate limbic stress responses, HRV tends to fall and symptoms like anxiety, ruminations and impaired focus rise
Why this matters for MUS and performance
Many MUS patients report difficulty concentrating, "brain fog", and emotional lability, even when brain imaging is "normal".
- Studies in depression, PTSD and anxiety show altered connectivity between PFC regions and autonomic outputs
- Reduced HRV and impaired inhibitory control mirror these connectivity issues
- NeuroFocus gives us a functional, task-based read-out of how the prefrontal system behaves under load – not just at rest
How NeuroFocus is used in HRU
Combined with NeuroFlow, this helps distinguish different fatigue patterns.
- Baseline prefrontal activation (under- vs over-driven)
- Ability to up-regulate and sustain oxygenation during a cognitive task
- Recovery dynamics once the task stops
- Distinguishes "tired because the brain is over-working to maintain control" from "tired because the system is under-activated and rigid"
What CoreScan measures
CoreScan is our advanced bioelectrical impedance analysis with alternating current conductivity (BIA-ACC). It uses surface electrodes on hand and foot to quantify body composition and hydration.
- Total Body Water (TBW) and its partition into Extracellular Water (ECW) and Intracellular Water (ICW)
- Fat Mass (FM), Skeletal Muscle Mass (SMM) and indices of lean vs adipose tissue
- Phase Angle (PA°) – reflects cell membrane integrity and tissue vitality
- Outputs rely on published multi-frequency equations, validated against reference methods in multiple populations
Why ECW, ICW and Phase Angle matter
Large clinical datasets show critical patterns in fluid distribution and cellular integrity.
- Higher ECW/TBW ratios are consistently associated with fluid overload, systemic inflammation, frailty and higher mortality across conditions
- Shifts from ICW → ECW signal loss of cellular hydration and metabolic efficiency, even before overt disease markers rise
- Lower phase angle is linked with worse outcomes in chronic inflammatory disease, sarcopenia and cachexia
- A large study of over 99,000 adults showed people with MUS have higher ECW, lower ICW, lower phase angle, altered cortisol rhythms and higher hs-CRP
How CoreScan is used in HRU
We quantify body composition and hydration patterns that correlate with different stress and MUS profiles.
- Whether a patient is "swollen but dehydrated" – high ECW, low ICW and low PA° despite "normal" body weight
- Whether their phenotype is lean-loss, fat-dominant or mixed matrix + fat – patterns that correlate with different stress and MUS profiles
- Whether body composition and hydration support or undermine recovery, cognition and pain processing
- Turns vague descriptions like "I feel puffy and exhausted" into objective hydric and matrix patterns that can be tracked over time
What TissueFlow measures
TissueFlow uses multiple electrodes across different body regions to measure regional extracellular bioimpedance and derives ΔECW – changes in extracellular water in specific anatomical "zones".
- Injects a very low-intensity, imperceptible current through the extracellular space
- Detects how each region's impedance changes following a standardised, mild stress stimulus
- Maps zones with ΔECW+ (extracellular fluid accumulation / edema) vs ΔECW− (extracellular dehydration / mineral loss)
- Tracks stress-recovery behaviour in each zone
Why the extracellular matrix matters
The extracellular matrix and interstitial fluid act as the buffer and transport medium between circulation and cells. Chronic inflammation and stress alter this space.
- Increased ΔECW and edema correlate with chronic inflammatory processes, catabolite build-up and sodium–aldosterone driven fluid retention
- Chronic inflammatory states are increasingly seen as a failure of resolution, with persistent interstitial fluid and lymphatic changes
- The original TomEEx work frames the device as a way to objectify vague and aspecific symptomatology
- Many MUS cases correspond to regional extracellular imbalances and chronic low-grade inflammation, especially when the stress-reaction system is in a state of exhaustion
How TissueFlow is used in HRU
TissueFlow identifies regional patterns that conventional medicine cannot detect.
- Identify specific regions (e.g. lumbar spine, pelvis, neck) with ΔECW+ suggestive of congested, inflamed tissues in patients with chronic pain or stiffness
- Detect areas in stress "exhaustion" – zones that fail to return to baseline impedance after a controlled stimulus, indicating impaired local regulation
- Relate these objective patterns to symptoms such as regional pain, heaviness, localised swelling, or "blocked" tissues – classic MUS presentations
- In combination with CoreScan, tells us not just how much extracellular water a person carries, but where, how it behaves under stress, and whether it is compatible with healthy adaptive reactions or chronic congestion
Taken together, NeuroFlow, NeuroFocus, CoreScan and TissueFlow give a multi-layered, quantitative view of processes that are strongly implicated in MUS and chronic "unexplained" complaints:
Autonomic Dysregulation
Lower HRV, blunted or chaotic stress rhythms, impaired recovery
Low-Grade Inflammation & Fluid Shift
Increased ECW/TBW, ΔECW+, matrix congestion without overt organ failure
Loss of Cellular Integrity
Reduced phase angle, altered body composition even in "normal-BMI" individuals
Prefrontal–Autonomic Integration Issues
Poor cognitive control over stress responses, contributing to fatigue, anxiety and "brain fog"
HRU does not diagnose disease and does not replace standard medical work-up. Instead, it:
- Translates a person's subjective experience ("I feel wired and exhausted", "I'm swollen and heavy", "my brain doesn't switch off") into objective patterns across stress axis, matrix and composition
- Tracks these patterns over time, allowing us to see whether interventions (e.g. sleep and circadian changes, nutritional shifts, targeted supplementation, biofeedback, physical therapy) are actually improving the underlying physiology
"In short, HRU is built to measure what conventional tools leave in the dark: the early, reversible disturbances in autonomic regulation, hydration, and tissue matrix that sit behind a vast amount of "medically unexplained" suffering."
Evidence Base
Scientific Validation & Medical Literature Support
The following peer-reviewed studies and long-term research projects support the physiological principles measured by HRU. These studies span performance science, clinical physiology, and applied human optimisation.
Nervous System Regulation & Stress Physiology
Chrousos GP, et al. (2022). PPG-determined HRV and extracellular water in the evaluation of chronic stress and inflammation. Hormones.
→ Validates PPG-HRV for stress assessment
Wiley CR, et al. (2025). The interplay between heart rate variability, inflammation, and lipid accumulation. Physiol Rep.
→ Links HRV to inflammatory load
Shaffer F, Ginsberg JP (2017). An overview of heart rate variability metrics and norms. Front Public Health.
→ Establishes HRV measurement standards
Cellular Function, Hydration & Tissue Readiness
Tsigos C, et al. (2015). Stress and inflammatory biomarkers and symptoms are associated with bioimpedance measures. Eur J Clin Invest.
→ Connects bioimpedance to stress physiology
Boschiero D, Semenzato A (2009). Stress, vague symptoms and chronic inflammation: TomEEx extracellular bioimpedance tomography. TomEEx Research.
→ Foundation for extracellular analysis
Perez-Morales R, et al. (2021). Extracellular water/total body water ratio as predictor of mortality in hemodialysis patients. Ren Fail.
→ ECW/TBW clinical significance
Lai TF, et al. (2025). Elevated extracellular water to total body water ratio and mortality. Clinical Research.
→ ECW as health predictor
Park KS, et al. (2021). ECW/TBW and sarcopenia. Aging Clin Exp Res.
→ Links hydration to muscle health
Medically Unexplained Symptoms
Marks E (2015). Medically unexplained symptoms: an acceptable term?. Br J Gen Pract.
→ Defines MUS clinical context
Jadhakhan F, et al. (2019). Prevalence of medically unexplained symptoms in adults. BMJ Open.
→ Establishes MUS prevalence
Husain M, et al. (2021). Medically unexplained symptoms: assessment and management. Clin Med.
→ MUS assessment approaches
* MUS prevalence data from BioTekna's Epidemiological Observatory
Our Foundation
Tested Over Time — Not Built Overnight
HRU is built on technologies and physiological principles that have been studied, refined, and applied for years across medical, sports, and performance environments. What is new is not the science — but the integration, structure, and accessibility of the data.
"HRU translates proven physiology into clarity, direction, and measurable change."
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