9. STRESS & FATIGUE Flashcards
This module covers: • Understanding stress. • Physiological effects of stress. • Stress in clinical practice. • Adrenals. • Natural approach to stress. • Understanding fatigue. • Mitochondria and fatigue. • Chronic fatigue and myalgic encephalomyelitis (ME).
Define stress and the impact chronic stress can have on health
Stress is defined as a non-specific response of the body to any disturbance / demand - triggering the ‘stress response’.
If stress is extreme or chronic, the stress response can be overwhelming and harmful to any body system (this is ‘distress’).
Name THREE causes of stress
- Poor nutrition: Nutritional deficiencies (e.g., highly-processed diets, high alcohol intake).
- Personal stress: Not feeling happy with oneself; financial problems; problems with family members, friends, at work.
- Poor body functions: Injury or illness e.g., allergy, skin conditions, thyroid disorders, chronic inflammatory disorders. Detoxification - slow or fast detoxification of certain NTs or hormones may result in imbalances in stress hormones (e.g., COMT / MAO).
- Environmental stressors: Radiation e.g., mobile phones, x-rays, microwaves; pesticides, industrial and household chemicals.
What is the general adaptation syndrome?
Name its stages.
A term coined by the endocrinologist, Hans Selye, that describes the 3 stages of a stress response which are controlled and regulated by the adrenal glands.
Alarm phase, resistance phase and exhaustion phase.
What happens during the alarm phase of the general adaptation syndrome?
Initial response, often referred to as ‘fight or flight’.
- Counteracts danger by mobilising resources for physical activity.
- Stressor → hypothalamus → sympathetic nervous system → adrenal medulla releases adrenaline and noradrenaline.
- Adrenaline activates inflammatory cytokines - ↑ oxidative stress.
- ACTH release (anterior pituitary) → cortisol release (adrenal cortex). Cortisol provides additional glucose, ↑ pain threshold and inhibiting immune responses.
ACTH - Adrenocorticotropic hormone
What happens during the resistance phase of the general adaptation syndrome?
- Once the stressor has gone the alarm phase abates and the individual returns to a state of equilibrium.
- The first two phases (alarm and resistance) occur repeatedly in life and are part of evolving as human beings.
What happens during the exhaustion phase of the general adaptation syndrome?
- If stress is prolonged or severe then equilibrium is not restored and exhaustion results.
- Prolonged release of stress hormones has negative health effects.
- Over time, cortisol levels especially decrease, leading to illness.
Why can hyperactivation of the HPAA have widespread effects? Name THREE possible consequences.
Glucocorticoid receptors are expressed in most organs and tissues including several brain regions, sympathetic nerves and immune cells.
Repeated surges of cortisol can lead to cortisol dysfunction, resulting in unmodulated inflammation, and various sequelae including:
- pain
- depression
- GI issues
- increased risk of cardiovascular disease
- cancer.
What are the proposed mechanisms underlying cortisol dysfunction and cortisol resistance?
- Glucocorticoid receptors are expressed in most organs and tissues. Prolonged or excessive cortisol secretion leads to desensitisation of glucocorticoid receptors to cortisol (cortisol resistance).
- Impaired binding disrupts negative feedback where cortisol would normally inhibit continued CRH release.
- CRH ↑ mast cell activation, release of noradrenaline (pro-inflammatory) and upregulates glutamate in the amygdala to promote a fear-based response to stress.
- High surges of cortisol increase its affinity to bind to mineralocorticoid receptors, where it has a pro-inflammatory effect.
CRH = corticotropinreleasing hormone
The connection between stress and inflammation. What conditions is stress-induced inflammation implicated in?
Inflammation is a key driver in the physiological effects of stress. Stress in turn increases inflammation. It’s a vicious cycle.
- Stress-induced inflammation is implicated in: CVD, fibromyalgia, chronic fatigue syndrome, osteoporosis, rheumatoid arthritis, IBD, chronic back pain, TMJ dysfunction and more.
- Inflammation increases oxidative stress and free radical damage, cellular death, ageing and systemic tissue damage.
TRUE or FALSE
The sympathetic stress response is pro-inflammatory, serving a purpose in the short term (destroys pathogens and foreign bodies).
True
In chronic stress situations, it contributes to the inflammatory state.
Explain how prolonged cortisol secretion increase the risk of insulin resistance and Type 2 diabetes
- Cortisol increases gluconeogenesis and decreases glycogen synthesis. Prolonged elevations lead to hyperglycaemia.
- Cortisol also inhibits beta cell insulin secretion and impairs insulin-mediated glucose uptake.
Explain how prolonged cortisol secretion leads to weight gain with central adiposity
- Cortisol stimulates appetite and intake of highly palatable foods.
- Impaired insulin response and consistently high blood glucose sends hunger signals to the brain leading to overeating.
- Causes redistribution / accumulation of fat in visceral fat cells.
Explain how prolonged cortisol secretion suppresses reproductive function
- Normal function is inhibited by various components of the HPAA in chronic stress.
- CRH suppresses the secretion of GnRH, disrupting pulsatile release of FSH and LH and in turn, oestrogen, progesterone and androgens.
Explain how prolonged cortisol secretion leads to impaired immune function
- Increases infection susceptibility.
- Decreases T-cell proliferation and downregulates T-helper cell receptor expression - necessary to induce Th1 immune response.
- Inhibits neutrophil, macrophage, NK cell and lymphocyte activity.
Explain how prolonged cortisol secretion suppresses thyroid function
- HPAA activation and ↑ cortisol = ↓ TSH production.
- Glucocorticoids inhibit T4 - T3 conversion (↓ 5-deiodinase activity).
- Thyroxine is shunted into the ‘inactive’ rT3.
- In adrenal fatigue, low cortisol ↓ T3 receptor responsiveness.
Explain how prolonged cortisol secretion suppresses gastrointestinal function
Ongoing stress leads to changes in the ‘gut-brain’ axis (this includes responses from the ANS and HPAA) causing:
- Altered GI motility (impairing digestion and elimination).
- Increased visceral perception.
- Changes in GI secretions - e.g., downregulates HCl production.
- Increased intestinal permeability to large antigenic molecules. It can lead to mast cell degranulation and colonic mucin depletion.
- Negative effects on microbiota and GI mucosal regeneration.
- Clinical consequences include GORD, peptic ulcers, IBD, SIBO etc.
Explain how prolonged cortisol secretion downregulates the endocannabinoid (eCB) system and how it is connected to mood
- The eCB system has various homeostatic roles including
-modulation of neural plasticity,
-neuroprotection,
-immunity,
-inflammation,
-pain,
-emotional memory,
-hunger
-metabolism. - Suboptimal function of the eCB is linked with conditions such as
-depression,
-fibromyalgia,
-migraine
-IBS. - Circulating eCBs are used in the crosstalk between the intestinal microbiome and brain - specifically influencing mood.
List FIVE typical symptoms and conditions linked to chronic stress
Examples of typical symptoms:
- Insomnia,
- fatigue,
- depression,
- irritability,
- headache,
- digestive disturbances.
Conditions linked to chronic stress include:
- Anorexia nervosa,
- asthma,
- autoimmunity,
- cancer,
- CVD,
- chronic fatigue syndrome,
- recurrent infections,
- mood disorders,
- Type 2 diabetes,
- IBS,
- ulcers,
- headaches,
- hypertension,
- menstrual irregularities,
- PMS,
- thyroid disorders.
Persistent stress initially leads to hyperactivation of the HPAA. Continued stress results in hypo-activation of the HPAA. List the symptoms of both.
Hyperactivation
- depression,
- anxiety disorders,
- metabolic syndrome (hyperglycaemia, hypertension, lipid abnormalities and central adiposity).
Hypo-activation
- fatigue,
- irritability,
- pain and associated disorders including chronic fatigue syndrome, fibromyalgia and arthritis.
What is the role of the androgen DHEA in the stress response?
- Alongside the release of glucocorticoids, noradrenaline and adrenaline, the androgen DHEA is also produced in larger amounts in response to stress.
- DHEA has been suggested to play a significant role in protection against the negative consequences of stress.
- Also protects against neurotoxic effects of chronically elevated cortisol on the hippocampus and reduces anxiety and depression.
What can ongoing stress with prolonged DHEA and cortisol release lead to?
a depleted state (referred to as ‘adrenal exhaustion’) with an impaired stress response and loss of resiliency.
Name SIX key signs and symptoms of adrenal ‘exhaustion’
- Fatigue and ↑ need for sleep,
- inability to cope with stress,
- anxiety,
- irritability,
- ↓ libido,
- lots of yawning,
- lower back pain,
- recurrent infections,
- sweet cravings,
- reactive dysglycaemia,
- sensitivity to cold and heat,
- lower body temperature,
- poor digestion,
- postural hypotension,
- unstable pupillary reflex.
How can adaptogens be useful for adrenal ‘exhaustion’? Name TWO adaptogens.
Act as mild stressors to cells, priming them to be able to effectively respond to stress (analogous to repeated physical exercise).
Protect against adrenal exhaustion and assist recovery.
- ashwagandha,
- Siberian and Korean ginseng,
- rhodiola.
General interpretation of adrenal stress index results:
- Normal levels of cortisol and DHEA
= normal (no stress)
General interpretation of adrenal stress index results:
- Raised cortisol and raised DHEA
= chronic stress
General interpretation of adrenal stress index results:
- Raised cortisol, normal DHEA
= normal short-term stress
General interpretation of adrenal stress index results:
- High cortisol, low DHEA
= first sign of adrenal ‘fatigue’
General interpretation of adrenal stress index results:
- Low cortisol, low DHEA
= adrenal ‘exhaustion’
General interpretation of adrenal stress index results:
- Low cortisol, normal DHEA
= start of recovery process
Nutritional approach to stress: discuss how an anti-inflammatory diet can be useful in reducing stress levels. Provide practical advice.
Inflammation drives stress and stress drives inflammation. Include:
‒ 8–10 portions of energetically balanced fresh fruit and vegetables, rich in vitamins, minerals and phytonutrients such as polyphenols, flavonoids and organosulphur compounds.
Nutritional approach to stress: discuss how stabilising blood glucose can be useful for chronic stress. Provide practical advice.
Drops in blood glucose trigger cortisol release; chronic stress increases hyperglycaemia risk:
– Complex carbohydrates - release glucose at a steady rate, high in fibre, rich in B vitamins e.g., whole grains and legumes.
Natural Approach to Stress: proteins.
Name THREE amino acids especially important for stress. Provide practical advice.
- 2–3 palm size portions of high quality protein e.g., legumes, nuts and seeds, whole grains, fish and eggs, to ensure amino acids required for neurotransmitter production.
- Especially tyrosine - adrenaline, noradrenaline, dopamine production e.g., nuts, seeds, whole grains, legumes, fish.
- Tryptophan - serotonin, melatonin precursor e.g., brown rice, quinoa, oats, fish, eggs, bananas.
- Glutamine - GABA (ensure B6, zinc, taurine) e.g., cabbage juice, asparagus, broccoli, turkey, bone broth. ↓ intestinal permeability. ½ cup cabbage juice or 1 cup bone broth daily.
Why is potassium to sodium ratio important for stress?
Provide practical advice.
- Ensure good intake of potassium-rich foods and reduce sodium intake.
- Stress hormones can cause reductions in serum potassium.
- Aim for a dietary potassium-to-sodium ratio greater than 5:1.
- Readily achieved with a diet rich in fruits and vegetables because most fruits and vegetables have a K:Na ratio of at least 50:1.
- Include 2 handfuls of dark green leafy veg daily (green smoothie).
How can we support microbiome during the times of stress?
Stress induces changes in the gut microbiota. Support this with:
- Prebiotic foods - dandelion greens, chicory, Jerusalem artichoke, garlic, etc.
- Probiotic foods - kimchi, sauerkraut, kombucha, kefir, yoghurt (cultured) etc.
- Polyphenol-rich foods (to feed commensals and support the mucosal barrier) - green tea, blueberries, cranberry, currants etc.
What foods/drinks should be avoided during stress?
- High fructose, artificial sweeteners, high-fat consumption especially damaged fats, high intake of animal and soy protein.
- Refined carbohydrates - alongside disruption to the microbiome, disturbs blood glucose regulation.
- Alcohol - a chemical stressor that impairs communication and processing pathways in the brain and contributes to mood and sleep disorders; depletes glutathione and Vitamin B1 - it is potentially neurotoxic.
- Caffeine - stimulates adrenaline and cortisol release, driving the stress response; blocks adenosine receptor activity inhibiting sleep.
Name herbal teas that relax the nervous system
- chamomile,
- lemon balm,
- passionflower,
- lime flower,
- hops.
Stress promotes a state of sympathetic nervous system dominance at the expense of digestion and rest. Provide practical advice on supporting digestion in a clinic.
- Encouraging abdominal breathing techniques before meals (↑ vagal stimulation as it passes through the diaphragm).
- Eating a fist-sized amount of bitter foods and herbs 15 minutes before meals e.g., rocket, dandelion greens, or use tinctures such as gentian. Bitters increase the release of gastric acid (vagal reflex) and prime pancreatic enzymes and bile. Apple cider vinegar - 1
tsp. in 100 ml water before main meals will have a similar action. - Mindful eating focusing on aroma, texture and taste, and chewing food well shifts thoughts away from stress and improves digestion.
How can we support the eCB system?
- Increase dietary intake of omega-3 fatty acids - required for normal eCB signalling and act as regulators of the eCB system.
- Polyunsaturated fatty acids play a fundamental role in the eCB system.
- Arachidonic acid is needed in the biosynthesis of eCBs.
NOTE: a surplus of omega-6 fatty acids and inadequate omega-3 (common in Western diets), causes excess synthesis of eCBs.
This leads to desensitised and downregulated eCB receptors.
-
Prebiotics and probiotics support the eCB system.
The eCB system interacts with the central and enteric nervous systems influencing gut motility, reducing GI inflammation and balancing the reaction to stress. - Black pepper, cinnamon, oregano, basil, lavender and rosemary contain the phytocannabinoid beta-caryophyllene.
- Cold water exposure has been shown to increase eCB levels.
- EVOO has been shown to upregulate CB1 receptors.
Nutrients to support stress
How does Vitamin C help with stress? Include dosage.
- Key water-soluble antioxidant in blood and tissues inclusive of CNS. Stress increases free radical damage.
- The CNS is especially sensitive to oxidative stress, which is in turn linked with ↑ psychosocial stress, anxiety and depression.
- Shown to improve recovery from mental stress.
- Adrenal support - is a co-factor in glucocorticoid synthesis.
- Vitamin C supplementation has shown to reduce stress-induced cortisol release. ↓ hyperactivation of the HPA-axis.
- Enhances immune function - upregulates natural killer cells, interferons and T-cells.
Dosage: 500 mg - 2 g daily.
