Stress and fatigue Flashcards
Describe the mechanism behind cortisol resistance and how this results in inflammation?
- Chronic stress leads to prolonged or excessive cortisol secretion, which leads to the desensitisation of glucocorticoid receptors (expressed in most organs and tissues) to cortisol (cortisol resistance)
- Negative feedback would normally inhibit continued corticotropin-releasing hormone release but the impaired binding means that CRH increases mast cell activation, release of noradrenaline (inflammatory) and upregulates glutamate.
- High surges of cortisol can lead to cortisol dysregulation which can have a pro inflammatory effect as it binds to mineralocorticoid receptors and can also cause pain, depression, GI issues and an increased risk of CVD and cancer.
Discuss the three stages of the stress response
1) Alarm phase (fight or flight)
-counteracts danger by redirecting resources for physical activity
- The hypothalamus tells the anterior pituitary to release adrenocorticotropic hormone which stimulates cortisol release from the adrenal cortex. Cortisol increases blood glucose and ups the pain threshold
- Adrenals release adrenaline ( activates inflammatory cytokines in case you are responding to a wound) and noradrenaline
2) Resistance phase
Once the stressor has gone the alarm phase subsides and everything calms down, but cortisol is still secreted. These first two phases happen repeatedly in life and are normal
3) Exhaustion phase
If the stress is prolonged or severe then equilibrium is not restored and exhaustion results, prolonged release of stress hormones mean levels decrease, especially cortisol and this can lead to illness
Discuss 5 effects of prolonged cortisol secretion?
1) Increased risk of type 2 diabetes and insulin resistance
- cortisol increases gluconeogenesis and raises blood glucose, leading to potential hyperglycemia
- Also inhibits insulin secretion- cortisol will always override insulin
2) Weight gain with central adiposity
- cortisol stimulate appetite of palatable foods
- Causes accumulation of fat in visceral fat cells
- consistent high blood glucose sends hunger signals to the brain and can cause overeating
3) Suppressed reproductive function
- CRH suppresses the secretion of GnRH, disrupting release of FSH, LH and in turn oestrogen , progesterone and androgens
4) Impaired thyroid function
- Reduced TSH production
- cortisol inhibits 5 deiodinase activity, impairing the conversion of thyroxine to triiodothyronine, and shunts thyroxine to inactive RT3
- in adrenal fatigue, low cortisol can decrease T3 receptor responsiveness
5) Suppresses gastrointestinal function, changes in the gut-brain axis
- Altered GI motility, impairing digestion and elimination
- Changes in GI secretions eg decreased HCI
- negative effects on microbiota and GI mucosal regenerative
6) Impaired immune function
- Inhibits neutrophil, macrophage, NK cell and lymphocyte activity
- decreases T cell proliferation and reduces Th1 immune response
What are the effects of both persistent and continued stress on the HPAA with examples of diseases?
- Persistent stress initially leads to hyperactivation of the HPAA and is associated with depression, anxiety and metabolic syndrome
- Continued stress results in hypoactivation of the HPAA and is linked with fatigue, irritability, pain, CFS, fibromyalgia and arthritis
What is adrenal exhaustion with key signs and symptoms?
The adrenal glands release glucocorticoids, noradrenaline and adrenaline and the androgen DHEA in response to stress, ongoing stress with prolonged DHEA and cortisol release leads to a depleted state ‘adrenal exhaustion’- impaired stress response and a loss of resiliency.
fatigue and increased need for sleep, inability to cope with stress, anxiety, low libido, lower back pain, recurrent infections, sweet cravings
How do adaptogens work?
Adaptogens act as mild stressors to cells, they are preparing them to be able to effectively respond to stress and can protect against adrenal exhaustion
Natural approach to stress: 5 dietary recommendations of things to include, and 3 of things to avoid
Include:
1) 8-10 portions of fruit and veg everyday, rich in vitamins, minerals and phytonutrients to protect against oxidative stress, high demand for vitamin C, dark leafy greens for magnesium
2) Complex carbohydrates to stabilise blood sugar and release glucose at a steady rate , so cortisol isn’t triggered . also rich in B vitamins whole grains and legumes
3) 2-3 palm size high quality protein eg legumes, fish, nuts, seeds, fish and eggs to ensure amino acids for neurotransmitter production especially tyrosine (adrenaline, noradrenaline, dopamine)
Tryptophan (serotonin, melatonin ) brown rice quinoa oats fish bananas
Glutamine for GABA cabbage juice asparagus broccoli bone broth
4) Support microbiota with prebiotic foods- dandelion greens, chicory, artichoke, garlic and probiotic foods- kimchi, saurkraut, kombucha, keffir
5) Polyphenol rich foods to feed commensals and support the mucosal barrier- green tea, blueberries, cranberry, currants
Avoid:
1) Refined carbohydrates- disrupts microbiome and blood glucose regulation
2) Alcohol- contributes to mood and sleep disorders, depletes glutathione and B vitamins
3) Caffeine- stimulates adrenaline and cortisol release, drives the stress response and inhibits sleep
4 ways to support the digestive system in a state of sympathetic nervous dominance?
1) Encourage abdominal breathing techniques before meals to stimulate vagus nerve
2) Eat a fist size amount of bitter foods and herbs 15 minutes before meals eg rocket, dandelion greens or gentian to increase stomach acid and prime pancreatic enzymes and bile
3) Take Apple cider vinegar 1 tsp in 100ml water before main meals to have similar action
4) Mindful eating, chew food well to sift thoughts away from stress and onto digestion
3 ways to nutritionally support the endocannabinoid system?
1) Increase dietary intake of omega 3 fatty acids- regulators and needed for signalling
2) Polyunsaturated fatty acids play a role in the eCB system
3) Arachidonic acid is needed in the biosynthesis of eCBs
Describe 5 specific nutrients you could use for stress with mechanisms?
1) Magnesium 200- 400mg, taurate, gycinate
- Co factor for GABA synthesis- reduces presynaptic glutamate release with a net anxiolytic effect
- Stress related muscle tension- can break the actin - myosin bond
- co factor for serotonin- melatonin pathway
- Taurine is a GABA agonist and Glycine is an inhibitory neurotranmitter so these forms may be even more useful
2) B complex vitamins ( high dose formula- 50-100mg/each)
- Co factors in krebs cycle- needed for ATP production
- B6 exerts modulatory effects on GABA and serotonin, regulates anxiety, pain and depression
B6, B9 and B12 role in methylation and support monoamine and catecholamine neurotransmitters
- As a complex can improve mood and quality of life
3) Vitamin C 500-2000mg
- Key water soluble antioxidant in blood and tissues. Stress increases free radical damage and the CNS is especially sensitive to oxidative stress
- Adrenal support- cofactor in glucocorticoid synthesis
- Can reduce stress induced cortisol release and decrease hyperactivation of the HPA axis
- enhances immune function
4) Vitamin E- 400-800 IU
- lipid soluble antioxidant so can protect neuronal cell membranes and myelin sheaths from oxidative stress
- protects the adrenal cortex from free radical damage and decrease stress induced release of cortisol
- supports immunity
5) Phosphatidyl serine 200-400mg
- Buffers HPAA response, allows better sleep mood and decreased anxiety
- mediates effect through normalisation of cortisol binding globulin
How can stress lead to unresolved chronic inflammation?
The sympathetic response to stress is pro inflammatory, with the purpose of destroying pathogens and foreign bodies.
Inflammation increases oxidative stress and free radical damage, cellular death and tissue damage.
stress induced inflammation is implicated in : CVD, fibromyalgia, CFS, osteoporosis, IBD, chronic back pain and more
4 herbs that you could use to support stress?
1) Chamomile
- mild anxiolytic and sedative effects
- relieves GI pain and complaints associated with stress
2) Passionflower
- anxiolytic properties and promotes restful sleep
- shown to increase resilience to stress, regulates GABA pathway
3) Lavender
- elevates mood, useful for depression
- essential oil interacts with the limbic system (deals with emotion and memory)
4) Ashwagandha
- Adaptogen and tonic, conserves energy and boosts energy reserves
- Is neuroprotective, sedative, anxiolytic (GABA agonist) and cognition enhancing
Which 5 things may contribute to mitochondrial dysfunction?
1) Nutrient deficiencies
2) Environmental toxins- mitochondria have high metabolic activity so are susceptible to toxin exposure
3) Oxidative stress in cells - mitochondria generate ROS which leak out. damage occurs when ROS outnumbers antioxidant activity
4) Hyperglycaemia- induces superoxide production in mitochondria leading to dysfunction
5) Inflammatory mediators eg TNF-a, increased ROS generation
Which antioxidants can protect the mitochondria from oxidative stress?
- superoxide dismutase (manganese)
- glutathione peroxidase (selenium)
- glutathione reductase (B3)
- Co enzyme Q10
- Vitamin E
What are 4 factors associated with increased mitochondrial damage?
1) ROS leaked whilst ATP is produced
2) Ageing (accumulated oxidative damage to mitochondrial DNA)
3) Genetic susceptibility
4) Toxic metals and pollutants
5) prescription drugs- antibiotics, aspirin, NSAIDS statins
