For Dr Anne Lucas, stress is not a problem in itself: the difficulty comes from its modern form, repeated, often psychological, with no real return to calm. This mismatch between very old biological circuits and an environment saturated with demands links chronic stress to fatigue, sleep disturbance, digestive symptoms and metabolic consequences.
Ancestral stress and modern stress
The physiology of stress has changed little: two axes are still mobilised, the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. What has changed is the nature of the stressor. Ancestral stress meant a brief physical threat, followed by a return to homeostasis. Modern stress is psychological, repeated and chronic: the body mobilises energy with no physical outlet, and that lack of resolution sustains the neurohormonal and metabolic overload.
The biochemistry of stress
The rapid response relies on the adrenal medulla (noradrenaline, adrenaline): reduced gut motility and secretions, rapid release of glucose, and substantial urinary loss of magnesium under the effect of adrenaline. The slower response runs through the HPA axis (CRH, ACTH, then cortisol): availability of glucose and fatty acids, alertness and, in the short term, a modulating action on inflammation. The key point is not only how much cortisol there is, but the loss of its circadian rhythmicity.
The three phases of stress
Alarm: immediate mobilisation (restlessness, hyperactivity, sugar cravings, digestive symptoms), with glycogenolysis and gluconeogenesis to supply glucose. Resistance: the stress continues, cortisol rises, DHEA falls, and a catabolic terrain sets in (morning fatigue, brain fog, disturbed sleep, rumination). The cortisol/DHEA ratio becomes central, particularly for muscle. Exhaustion: cortisol, DHEA and pregnenolone all fall, with marked vulnerability and a heavier clinical picture.
Chronic stress and metabolic health
Cortisol drives a catabolic environment: muscle releases glucogenic amino acids (alanine, glutamine) for gluconeogenesis, hence a loss of muscle mass that matters a great deal for long-term health. Repeated hyperglycaemia leads to compensatory hyperinsulinaemia and then insulin resistance; stress also disrupts insulin signalling (serine phosphorylation of IRS1, the PI3K-AKT pathway, GLUT4 exocytosis). Finally, cortisol promotes redistribution of adipose tissue towards the visceral compartment, via visceral lipoprotein lipase and 11β-HSD1 (conversion of cortisone into active cortisol), hence android obesity and a raised waist circumference, one criterion of metabolic syndrome.
Sleep and neurotransmission
The rhythms of cortisol and melatonin run in opposite directions: cortisol that is too high in the evening makes falling asleep difficult. Chronic stress also diverts tryptophan towards the indole pathways, at the expense of serotonin and then melatonin (anxiety, sugar cravings, disturbed sleep). Lastly, it reduces sensitivity at GABA receptors, the main inhibitory neurotransmitter, hence irritability, hypervigilance and inner tension.
The gut-brain axis
Stress acts on the gut-brain axis through four routes (the vagus nerve, endocrine, immune, and metabolic via postbiotics and short-chain fatty acids). Persistently high cortisol degrades digestive quality, lowers secretory IgA and favours dysbiosis, permeability, LPS translocation, systemic inflammation and neuroinflammation. Hence the value of strengthening the gut barrier and rebalancing the microbiota.
Assessing stress and its phase
Assessment combines clinical signs (alarm, intermediate phase, exhaustion), questionnaires (PSS-10 for stress, MBI for burn-out, visual scales for fatigue and sleep) and functional biology. The salivary cortisol cycle across five samples (on waking, +30 min, midday, late afternoon, evening) makes it possible to see the rhythmicity and to spot circadian reversals.
The main levers for care
- Support steroidogenesis: cholesterol as precursor, mitochondrial function, thyroid function, iron status.
- Correct magnesium: a priority micronutrient, in a well-tolerated and bioavailable form, spread across the day.
- Chronobiological eating: a breakfast rich in protein and good fats, with no sugar; protein at every meal; carbohydrates placed in the afternoon to support serotonin and melatonin; a light evening meal, with no alcohol or stimulants.
- Physical activity matched to the phase: resistance training and zone 2 cardio during the overload phase, moderate effort in the intermediate phase, walking and gentle mobility in burn-out.
- Support the gut-brain axis: digestive enzymes, mucosal support, microbiota balance, cardiac coherence breathing, work on the parasympathetic system.
The aim remains to pair a symptomatic response with work on the underlying terrain, individualised according to the phase.
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