Naturopathic Nutrition Year 2 Stress and Fatigue PDF

Naturopathic Nutrition Year 2 Stress and Fatigue © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 1  Learning Outcomes In this lecture, you will learn about: Understanding stress. Physiological effects of stress. Stress in clinical practice. Adrenals. Natural a...

Naturopathic Nutrition Year 2 Stress and Fatigue © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 1  Learning Outcomes In this lecture, you will learn about: 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). © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 2  Understanding Stress Stress is defined as a non-specific response of the body to any disturbance / demand — triggering the ‘stress response’. The demand or ‘stressor’ can be positive (e.g., a new job, new relationship) or negative (e.g., fear, injury). A degree of stress is a normal part of life and can provide the impetus for action or change. However, if stress is extreme or chronic, the stress response can be overwhelming and harmful to any body system (this is ‘distress’). ‘Distress’ can significantly impact health and wellbeing. Identifying the cause of one's stress is fundamental in naturopathy. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 3  Understanding Stress Causes of stress: Poor nutrition: Nutritional deficiencies (e.g., highly-processed diets, high intake of alcohol). 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. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 4  Understanding Stress The general adaptation syndrome — 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: 1. Alarm phase (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. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 5  Understanding Stress The general adaptation syndrome (cont.): 2. Resistance phase: Once the stressor has gone the alarm phase abates and the individual returns to a state of equilibrium. The first two phases occur repeatedly in life and are part of evolving as human beings. 3. Exhaustion phase: 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. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 6  Physiological Effects of Stress If the stressor is perceived as too intense or the duration is too long, maladaptive responses occur, which can lead to disease. Glucocorticoid receptors are expressed in most organs and tissues including several brain regions, sympathetic nerves and immune cells. Thus, continued stimulus causing hyperactivation of the HPAA can have widespread effects. Repeated surges of cortisol can lead to cortisol dysfunction, resulting in unmodulated inflammation, and various sequelae including pain, depression, GI issues and increased risk of cardiovascular disease and cancer. HPAA = hypothalamic- (Hannibal & Bishop, 2014; Rehm et al. 2021) pituitary-adrenal axis © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 7  Physiological Effects of Stress Proposed mechanisms underlying cortisol dysfunction: 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 CRH = to bind to mineralocorticoid receptors, corticotropin- releasing hormone where it has a pro-inflammatory effect. (Hannibal & Bishop, 2014) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 8  Physiological Effects of Stress 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. The sympathetic response to stress is pro-inflammatory, serving a purpose in the short term (destroys pathogens and foreign bodies). In chronic stress situations it contributes to the inflammatory state. (Rehm et al. 2021) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 9  Physiological Effects of Stress Effects of prolonged cortisol secretion: Increased 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. Weight gain with central adiposity: Cortisol stimulates appetite and intake of highly palatable foods. Causes redistribution / accumulation of fat in visceral fat cells. Impaired insulin response and consistently high blood glucose sends hunger signals to the brain leading to overeating. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Adam et al. 2010; Geer et al. 2014) 10  Physiological Effects of Stress Effects of prolonged cortisol secretion (cont.): 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. Impaired immune function: Increases infection susceptibility. Decreases T-cell proliferation and downregulates T-helper cell receptor expression — necessary to induce Th1 immune response. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Charmandari et al. 2003; Dhabhar, 2014) 11  Physiological Effects of Stress Effects of prolonged cortisol secretion (cont.): Impaired immune function (cont.): Inhibits neutrophil, macrophage, NK cell and lymphocyte activity. Suppresses thyroid function: HPAA activation with increases in cortisol is associated with reduced TSH production. Glucocorticoids inhibit 5-deiodinase activity, which converts thyroxine to triiodothyronine. Thyroxine is shunted into the ‘inactive’ rT3. In adrenal fatigue, low cortisol ↓ T3 receptor responsiveness. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Charmandari et al. 2003) 12  Physiological Effects of Stress Effects of prolonged cortisol secretion (cont.): 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 regenerative. Clinical consequences include GORD, peptic ulcers, IBD, SIBO etc. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Konturek et al. 2011) 13  Physiological Effects of Stress Effects of prolonged cortisol secretion (cont.): Downregulates the endocannabinoid (eCB) system: The eCB system has various homeostatic roles including modulation of neural plasticity, neuroprotection, immunity, inflammation, pain, emotional memory, hunger and metabolism. Suboptimal function of the eCB is linked with conditions such as depression, fibromyalgia, migraine and IBS. Circulating eCBs are used in the crosstalk between the intestinal microbiome and brain — specifically influencing mood. (McPartland et al. 2014; Deroon-Cassini © CNM: Nutrition 2: Stress and Fatigue. SM / DC. et al. 2020; Jansma et al. 2021) 14  Stress in Clinical Practice Clients can present with myriad symptoms that trace back to stress as the key underlying or perpetuating factor. Examples of typical symptoms: Insomnia, fatigue, depression, irritability, headache, and 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 and thyroid disorders. Assessing client stress levels is a vital part of the consultation. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Gruner & Hechtman, 2012) 15  Stress in Clinical Practice Persistent stress initially leads to hyperactivation of the HPAA and is commonly associated with issues such as depression, anxiety disorders and metabolic syndrome (hyperglycaemia, hypertension, lipid abnormalities and central adiposity). Continued stress results in hypo-activation of the HPAA and is linked with fatigue, irritability, pain and associated disorders including chronic fatigue syndrome, fibromyalgia and arthritis. Functional testing can be valuable in (Helhammer et al., 2014; determining where on the continuum the client sits. Ciaramella et al. 2016) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 16  DHEA = dehydroepiandrosterone Adrenals (a precursor to sex hormones) The adrenal glands play an integral role 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. Ongoing stress with prolonged DHEA and cortisol release leads to a depleted state (referred to as ‘adrenal exhaustion’) with an impaired stress response and loss of resiliency. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Sripada et al. 2013) 17  Note: Many present with mixed Adrenals patterns of low / high cortisol as they head towards adrenal exhaustion Adrenal ‘exhaustion’ — key signs and symptoms include: 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. The role of 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 e.g., ashwagandha, Siberian and Korean ginseng, rhodiola. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 18  Review Nutrition Adrenals 2, Assessment & Diagnostics General interpretation of adrenal stress index results: Normal levels of cortisol and DHEA = normal (no stress). Raised cortisol, normal DHEA = normal short-term stress. Raised cortisol and raised DHEA = chronic stress. High cortisol, low DHEA = first sign of adrenal ‘fatigue’. Low cortisol, low DHEA = adrenal ‘exhaustion’. As seen in sample report. Low cortisol, normal DHEA = start of Indicates adrenal exhaustion. recovery process. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 19  Natural Approach to Stress Nutritional approach: Apply the CNM Naturopathic diet and adjust accordingly. Focus on an anti-inflammatory diet — 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. Stabilise blood glucose — 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. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 20  Natural Approach to Stress Nutritional approach — protein: 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. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 21  Natural Approach to Stress Nutritional approach — potassium to sodium ratio: Ensure good intake of potassium-rich foods and reduce sodium intake. Chronic stress and anxiety are associated with decreased levels of potassium. 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). © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 22  Natural Approach to Stress Nutritional approach — microbiome support: 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. Avoid: Refined carbohydrates, high fructose, artificial sweeteners, high fat consumption especially damaged fats, alcohol, high intake of animal and soy protein. (Rogers et al. 2016) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 23  Natural Approach to Stress Nutritional approach — Avoid: 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. Replace with herbal teas that relax the nervous system. Includes chamomile, lemon balm, passionflower, lime flower, hops. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 24  Natural Approach to Stress Stress promotes a state of sympathetic nervous system dominance at the expense of digestion and rest. Focus on supporting digestion by: Encouraging abdominal breathing techniques prior to 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 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. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 25  Natural Approach to Stress Nutritional approach — supporting the eCB system: eCB = endocannabinoid Increase dietary intake of omega-3 fatty acids. Polyunsaturated fatty acids play a fundamental role in the eCB system. Arachidonic acid is needed in the biosynthesis of eCBs. However, 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. Omega-3 fatty acids are required for normal eCB (McPartland et al. 2014) signalling and act as regulators of the eCB system. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 26  Natural Approach to Stress Supporting the eCB system (cont.): 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. Inclusion of pre and probiotic foods and probiotic supplementation supports the eCB system. 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. 27 © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (McPartland et al. 2014; Fidyt et al. 2016)  Natural Approach to Stress Specific nutrients: Nutrient: Functions: Vitamin C Key water-soluble antioxidant in blood and tissues inclusive (ascorbic of CNS. Stress increases free radical damage. acid) The CNS is especially sensitive to oxidative stress, which is in turn linked with Dosage: 500 ↑ psychosocial stress, anxiety and depression. mg — 2 g daily. 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. (Moritz et al. 2020) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 28  Natural Approach to Stress Specific nutrients (cont.): Nutrient: Functions: Vitamin B5 As a precursor to coenzyme A plays an (pantothenic essential role in adrenal cortex function. acid) Increases production of glucocorticoids Dosage: 100- and other adrenal hormones. 300 mg / day. Thought to reduce secretion of cortisol in times of stress. Vitamin B6 Exerts modulatory effects on GABA and (pyridoxine) serotonin, neurotransmitters that regulate Dosage: 50- anxiety, depression and pain perception. 100 mg / day. Downregulates activity of glucocorticoid receptors, ↓ the physiological impact of corticosteroid release. 29 © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Gruner & Hechtman, 2012; Pouteau et al. 2018)  Natural Approach to Stress Specific nutrients (cont.): Nutrient: Functions: B complex Co-factors in the Krebs cycle — needed for ATP production. vitamins Required to maintain nervous system health — B1 in particular enables the brain to utilise glucose. High dose combination. Vitamins B6, B9 and B12 have specific roles in methylation and decarboxylation processes that support synthesis of monoamine and catecholamine neurotransmitters. B group vitamins taken as a complex have been shown to improve mood and quality of life in individuals experiencing depression and anxiety. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Gruner & Hechtman, 2012; Lewis et al. 2013) 30  Natural Approach to Stress Specific nutrients (cont.): Nutrient: Functions: Vitamin E Acute and chronic stress increase free radical formation, especially in the CNS and adrenal cortex. Dosage: 400–800 iu / As a lipid soluble antioxidant, vitamin E protects neuronal day. cell membranes and myelin sheaths from oxidative stress. Has been shown to protect the adrenal cortex from free radical damage and decrease stress-induced release of cortisol. Supports immunity — increases phagocyte activity and promotes differentiation of immature T-cells in the thymus. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Anderson, 2008) 31  Natural Approach to Stress Specific nutrients (cont.): Nutrient: Functions: Magnesium Deficiency upregulates HPA activity, while supplementation (as citrate, attenuates activity with reductions in ACTH and cortisol. taurate, Is a co-factor for GABA synthesis, heightens glycinate). GABAergic availability by reducing presynaptic Dosage: glutamate release — net effect anxiolytic. 100–400 mg Is a co-factor in the serotonin-melatonin pathway. / day. Stress-related muscle tension — breaks actin-myosin bond. Amino acid chelates — taurate / glycinate: Taurine is a GABA agonist and glycine acts as an inhibitory neurotransmitter, so potentially even more useful. (Sartori et al. 2012; Boyle et al, 2017; © CNM: Nutrition 2: Stress and Fatigue. SM / DC. Kirkland et al. 2018) 32  Natural Approach to Stress Specific nutrients (cont.): Nutrient: Functions: Phosphatidyl- Normalises stress response. serine (PS) Buffers HPAA response, restoring normal ACTH and cortisol activity, allowing for better quality Dosage: 200– sleep, decreased anxiety and improved mood 400 mg / day. The effect is believed to be mediated through normalisation of cortisol binding globulin (CBG). L-theanine L-theanine (N-ethyl-L-glutamine) is a major amino acid uniquely found in green tea. L-theanine Dosage: 20–- increases brain serotonin, dopamine, GABA levels, 400 mg / day. supporting cognitive function and aiding relaxation. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Helhammer et al. 2014) 33  Natural Approach to Stress Specific nutrients (cont.): Therapeutic uses: Reishi mushroom Regarded as an adaptogen. Ganoderma Triterpene constituents have a lucidum sedative action, calming the nervous system to support relaxation and sleep. Dosage: 3–9 g / Contains polypeptides that act as day. Use as a powder in tea, precursors to neurotransmitters and food, capsules. endorphins supporting the stress response Considered non- Assists the immune system at times of stress edible; has a bitter, including increased number and activity of woody taste. NK cells, macrophages and T-lymphocytes. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Mukai et al. 2014) 34  Natural Approach to Stress Herbal support for stress: Key herbal strategies are aimed at calming heightened nervous system activity and supporting resistance to stress. Herbs can be used as infusions — 2 teaspoons of dried herb infused for 10 minutes in just boiled water, 2–3 cups daily. For herbal products follow dosages as per label recommendations. Nervine relaxants and mild sedatives calm the nervous system and promote restful sleep. Adaptogens increase the body’s resistance to stress through modulation of hormone and neurotransmitter physiology. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 35  Natural Approach to Stress Herbal support for stress (cont.): Therapeutic uses: Chamomile Has mild sedative and anxiolytic effects and has Matricaria recutita demonstrated benefits in alleviating symptoms flowers associated with generalised anxiety disorder. Relieves GI pain and spasm and is particularly helpful for GI complaints associated with stress. Passionflower Has anxiolytic properties and promotes restful sleep. Passiflora incarnata Shown to increase resistance to stress aerial parts (i.e., ↑ resilience), with improvements in inner restlessness, fear, sleep disturbance and exhaustion. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Mao et al. 2016; Gibbert et al. 2017) 36  Natural Approach to Stress Herbal support for stress (cont.): Therapeutic Uses: Lavender Elevates mood; useful for depression Lavandula especially where accompanied by officinalis restlessness, insomnia or anxiety. flowers, The essential oil interacts with the limbic essential oil system (deals with emotion and memory). Lemon balm Mild sedative and antispasmodic properties (relaxes Melissa officinalis smooth muscle) and is used traditionally for insomnia, aerial parts anxiety, irritability, depression, colic, nervous dyspepsia. 300–600 mg Effect thought to be by inhibition of GABA transaminase system, raising levels of GABA. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Cases et al. 2011) 37  Natural Approach to Stress Herbal support for stress (cont.): Therapeutic uses: Ashwagandha Is both adaptogen and tonic — conserves Withania somnifera energy and boosts energy reserves. root In the CNS is neuroprotective, sedative, anxiolytic (GABA agonist), and cognition enhancing. Shown to increase physical capability as well as improving psychological parameters. Siberian ginseng Helps the body to counteract and adapt to stress. Eleutherococcus Improves mental and physical performance senticosus and minimises negative effects of stress. root Enhances immunity, esp. NK cells and T-helper cells. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Bone & Mills, 2013) 38  Natural Approach to Stress Other strategies: Exercise: Facilitates regulation of the HPAA, and influences neurotransmitters associated with mood such as dopamine and serotonin. ‒ Include regular physical activity (several times a week), e.g., walking, jogging, Pilates. Natural therapies: Acupuncture, aromatherapy, massage, reflexology, cranial osteopathy, Bach flowers, homeopathy etc. Other ways of reducing stress: Optimise sleep hygiene, avoid reading / listening to bad news, talk to a friend, go for a walk in daylight, reduce blue light, fulfil responsibilities you have. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Gruner & Hechtman, 2012; Jackson, 2013) 39  Natural Approach to Stress Other strategies — establish a purpose / goal in life of your client: Purpose in life (Japanese ikigai) plays a major role in longevity. It acts as a buffer against stress and helps reduce overall inflammation. Facilitate / explore this concept with your clients. Work out life goals, how to achieve them and how to overcome hurdles. Achieving goals helps to overcome stress and, therefore, disease. Work on future goals rather than over-evaluation of the past. Overcoming hurdles is part of life. It creates a sense of fulfillment. 40 © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Ishida & Okada, 2006; Alimujiang et al. 2019)  Natural Approach to Stress A practical approach to solving stress / problems: 1. Ask your client: Write down all problems you have: Personal, work, financial, feeling overwhelmed, relationship difficulties etc. 2. Ask then: Read them over asking yourself: “How do I solve them”? 3. Get the client to solve the easy ones first — one step at a time. 4. Support the client in working out how to solve the bigger problems by breaking them down. 5. Encourage to seek additional support if needed, e.g., financial advice. 41 © CNM: Nutrition 2: Stress and Fatigue. SM / DC.  Natural Approach to Stress A practical approach to solving stress / problems (cont.): Steer client away from indecisive language: e.g., “I try, I hope, I am not sure”. e.g., focusing on the obstacles. Instead you should: Encourage your client to take control. Get your client to focus only on solutions and positive things. Acknowledge every progress made, small or large. Encourage your client to keep pushing forward, further and further to make the changes they desire. 42 © CNM: Nutrition 2: Stress and Fatigue. SM / DC.  Exercise: Case Study Jill, 38 years, buyer for a grocery chain, average 50 hours / week. Presents with: 4 months — stress and anxiety, difficulty falling asleep, bloating and discomfort on eating, ‘tired but wired’. Observations: Slight tremor and tongue quivers on protrusion. Tests: Salivary cortisol — low am with increase pm. Diet: Coffee x 3 / day milk +1 sugar, water x 4 glasses, wine x 2 glasses most nights to ‘wind down’. Often skips breakfast. Sandwiches (cheese or egg), mostly vegetarian, few legumes or nuts. Rice or pasta and fresh veg for dinner. History: Mild hypertension 3 years. No medication or supplements. Provide a brief naturopathic plan based on the information provided. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 43  Understanding Fatigue Fatigue = physical and mental exhaustion that is not relieved by rest. Fatigue is the symptom experienced when energy demand exceeds energy delivery. If more energy is spent than can be generated, it will lead to death! Thus, the body manifests uncomfortable symptoms to prevent this happening. While mild fatigue can be caused by a range of factors, moderate to severe persistent fatigue involves cellular energy systems — the hallmark of chronic fatigue syndrome and other intractable fatigue states. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 44  Mitochondria and Fatigue Mitochondria make over 90% of the body’s energy as ATP. This energy is crucial to sustain life and support organ function. Mitochondrial energy production is the result of two closely coordinated metabolic processes — the Krebs cycle and electron transport chain. If cells function slowly, then organs function slowly i.e., the start of organ failures such as heart failure and dementia. If the immune system functions slowly then healing and repair is slow, increasing risk of infection and cancer. If all cells in the body are affected, the clinical picture of chronic fatigue syndrome and premature ageing emerges. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 45  Mitochondria and Fatigue ATP cannot be stored — therefore, the mitochondria need to function continuously, every second of every day. Mitochondria are highly susceptible to nutrient deficiencies, environmental toxins and oxidative damage. Environmental toxins — mitochondria have very high metabolic activity so are particularly susceptible to toxin exposure. Oxidative stress in cells — the primary source of ROS are those generated by the mitochondria themselves, which leak out. Mitochondrial damage occurs when ROS production outpaces antioxidant activity. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Pizzorno, 2014) 46  Mitochondria and Fatigue Mitochondrial dysfunction (cont.): Hyperglycaemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Inflammatory mediators such as TNF-α have been associated with mitochondrial dysfunction and increased ROS generation. ‒ Consider why inflammatory mediators are raised, e.g., intestinal mucosal degradation (LPS leakage), pro-inflammatory diet (high omega 6:3 etc.), glucose dysregulation, raised homocysteine (increases TNF-α expression), TNF SNP, smoking, obesity, etc. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Gerő et al. 2016) 47  Mitochondria and Fatigue Primary ways mitochondria are protected from oxidative stress: Optimising levels of antioxidant enzymes — superoxide dismutase (manganese), glutathione peroxidase (selenium), glutathione reductase (B3), catalase (iron). Coenzyme Q10, vitamin E. Factors associated with increased mitochondrial damage: ROS leaked while ATP is produced. Ageing (accumulated oxidative damage to mitochondrial DNA). Genomic susceptibility. Toxic metals, persistent organic pollutants (POPs), alcohol. Many prescription drugs e.g., antibiotics, aspirin, NSAIDs, statins. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Filler et al. 2014 ; Pizzorno, 2014) 48  Mitochondria and Fatigue Key nutrients required for atp production (other than oxygen): Glycolysis Magnesium, vitamin B3 — in the cytosol. Acetyl CoA Vitamin B1, alpha-lipoic acid, vitamin B5. formation Krebs cycle Magnesium, manganese, iron, B1, B2, B3. Electron Transport Iron (complex I and III), vitamin B2 (complex I), Chain (ETC) sulphur (complex I), CoQ10 (complex II — transports high energy electrons), copper (complex IV). β-oxidation of fats Carnitine to transport fatty acids is most crucial. Energy carriers Vitamin B3 (or tryptophan and aspartic acid) — NAD (temporarily capture Vitamin B2 — FAD energy) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Pizzorno, 2014) 49  Mitochondria and Fatigue Key strategies to improve mitochondrial function: Optimise nutrients required for ATP production and antioxidant properties to protect the mitochondria from oxidative stress. Focus on blood sugar regulation (prevent chronic hyperglycaemia). Reduce levels of inflammatory mediators — optimise intestinal health, anti-inflammatory foods, optimise weight etc. Decrease toxin exposure e.g., consume organic food, avoid plastic packaging, carefully select cleaning products, cosmetics and personal care items; avoid alcohol and pharmaceuticals. Strength training — increase muscle mass to increase mitochondria number and function. (Pizzorno, 2014) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 50  ET = electron Mitochondria and Fatigue transport Essential nutrients for mitochondrial function: Nutrient: Functions: Coenzyme Transports high energy electrons in the ETC supporting Q10 mitochondrial function and energy production. Deficiency reduces ATP production and increases electron loss causing increased oxidative damage and fatigue. Production of ROS, which can damage Dosage: cellular lipids, proteins and DNA, is a 100–300 mg direct consequence of the ET process. / day CoQ10 is an efficient intra-mitochondrial (solubilised) antioxidant, playing a vital role in neutralising ROS. Ability to produce CoQ10 strongly correlates with longevity. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Nicolson, 2014; Pizzorno, 2014) 51  Mitochondria and Fatigue Essential nutrients for mitochondrial function (cont.): Nutrient: Functions: Alpha lipoic Is a co-factor for several mitochondrial acid (ALA) enzymes involved in glucose Dosage: oxidation and ATP generation. 300–600 mg / As an antioxidant, protects day. mitochondrial structures. Acetyl L- Essential for the transport of long chain fatty carnitine. acids across the mitochondrial membrane for Dosage: subsequent β-oxidation and generation of ATP. 500–2000 mg Increases mitochondrial oxidative phosphorylation, / day. thereby increasing ATP production and reducing mtROS. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Nicolson, 2014; Pizzorno, 2014) 52  Mitochondria and Fatigue Essential nutrients for mitochondrial function (cont.): Nutrient: Functions: Magnesium Plays a fundamental role in energy production where it (as citrate or transfers phosphate groups between ADP and ATP. malate). Magnesium insufficiency or deficiency can result in a symptom picture reflective of chronic fatigue syndrome. Dosage:200 ‒400 mg / day. Malic acid is a Krebs cycle cofactor, so magnesium malate may be better, and is researched to improve fibromyalgia. B complex B1 is needed in the Krebs cycle. B2 (energy carriers FAD, vitamins FMN) and B3 (coenzymes NAD and NADP). Required for High dose Krebs cycle and for conversion of fatty acids to ATP. combination. Possibly consider even higher even dose B2/B3 — 100mg+ © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 53  CFS and ME CFS = chronic fatigue syndrome. ME = myalgic encephalomyelitis. CFS and ME are terms often used interchangeably though ME is sometimes defined as CFS + inflammation. Characterised by long-term physical and cognitive fatigue, not alleviated by rest. Other symptoms include post-exertional malaise, muscle and joint pain, unrefreshing sleep, flu-like symptoms with sore throat and tender lymph nodes, mood disturbances. While mitochondrial dysfunction is recognised as a key player, there are a number of proposed contributing factors. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 54  CFS and ME Proposed aetiologies: Infectious organisms — in particular EBV (high antibody titres in patients with symptoms indicative of CFS). Other: Human herpes virus-6, Borrelia burgdorferi (Lyme’s). Immunological — e.g., increased cytokines, NK cell abnormalities, decreased CD8 suppressor cells. Imbalances that collectively suggest chronic, low level activation of the immune system. Abnormal HPAA functioning — association with hypocortisolism. Mitochondrial dysfunction and high oxidative stress — associated with ↓ GPO and SOD. Also low melatonin (sleep dysregulation). Consider polymorphisms in antioxidant or detox pathways. (Hechtman & Naik, 2012; Maes et al. 2013; © CNM: Nutrition 2: Stress and Fatigue. SM / DC. Lee et al. 2018; Noda et al. 2018) 55  CFS and ME Proposed aetiologies: Serotonin studies have concluded: ‒ Increased 5-HT autoimmune activity is associated with activation of inflammatory pathways and increased bacterial translocation. A reduction in 5 HT neurons has been noted. ‒ Proposed upregulation of the serotonin transporter (5-HTT) in astrocytes, reducing extracellular serotonin (5-HT) levels. A breakdown in the bidirectional communication between the brain and the gut mediated by bacteria and their metabolites. CFS / ME are commonly associated with GI symptoms (see next slide). (Maes et al. 2013; Lee et al. 2018; Noda et al. 2018) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 56  CFS and ME Proposed aetiologies (cont.): Findings in relation to intestinal health and CFS: – High relative abundance of bacterial species such as clostridium and ruminococcus in CFS / ME; decreased faecalibacterium abundance. – Metabolic endotoxaemia as a driver for CFS / ME. Microbes that cause dysbiosis can alter the immune system and disregulate mitochondrial function. Further, CNS manifestations are thought to relate in part to increases in neurotoxic ammonia and D-lactic acid-producing gut bacteria. (Brown, 2017; Nagy-Szakal et al. 2017; Newberry et al. 2018; Haß et al., 2019) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 57  CFS and ME Natural approach to CFS / ME — avoid: Caffeine (coffee, tea, chocolate, energy drinks). Temporarily counters fatigue, but the effect is short-lived and places strain on the adrenal glands exacerbating an already fatigued body. Sugar — an immune system depressant. Destabilises blood glucose causing peaks and troughs in energy. Artificial sweeteners — interact with sweet receptors to trigger insulin release (destabilise blood glucose). Aspartame contains excitotoxins (e.g., aspartates) and methanol, which converts to formic acid — a neurotoxin. Can worsen neurological symptoms. Alcohol — worsening of symptoms, depletes body of nutrients. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Hechtman & Naik, 2012) 58  CFS and ME Natural approach to CFS / ME — include (cont.): Good quantities of essential fatty acids: – Omega-3 is especially important for the activity of the mitochondrial membrane. EPA — anti-inflammatory properties and increases mitochondrial growth, size and distribution. DHA — essential for the structure of ETC complexes. – Most notable benefits observed are improvements in cognitive function and reduction in relapse frequency. Sufficient protein to allow for immune cell restoration and function. Individualised immune support (e.g., anti-microbials, vitamin C etc.) and GI support (e.g., digestive bitters, pro and prebiotics etc.). © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Hechtman & Naik, 2012) 59  CFS and ME Nutritional ketosis in CFS / ME — considered a beneficial dietary strategy for supporting mitochondrial function. Total carbohydrate intake < 50 g / day (or whatever is needed to get into ketosis). Moderate protein intake, around 1.5 g / kg bodyweight per day. Fuel as ketones come from fat AND the fermentation of fibre in the large bowel to short chain fatty acids. Typical macronutrient ratio — 75% fat, 20% protein, 5% carbohydrate. Changes the body’s primary fuel source from glucose to ketones. Ketones enter the mitochondria of body tissues for ATP production. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 60  CFS and ME Benefits of a ketogenic diet: mitohormesis = low concentrations While excess levels of mitochondrial ROS of mitochondrial (mtROS) are associated with mitochondrial stress increase dysfunction, low concentrations of mtROS can act health and viability within cells as signalling molecules, upregulating mitochondrial capacity and antioxidant defence — known as mitohormesis. Ketosis causes a significant shift in energy metabolism increasing reliance on mitochondrial respiration ― this induces mitohormesis. Further, in addition to their role as energy substrates, ketones (especially β-hydroxybutyrate) act as signalling molecules increasing expression of antioxidant enzyme systems. (Miller et al. 2018) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 61  CFS and ME Herbal approach to CFS / ME: Nutrient: Functions: Liquorice Suboptimal HPAA function and low cortisol is a common Glycyrrhiza feature of CFS / ME. Liquorice is an adrenal cortex glabra 1‒2 tsp restorative, supporting cortisol production and ↓ fatigue. powder daily. Anti-inflammatory activity — research indicates inhibitory effects on ROS-induced tissue inflammation and the COX, LOX and NF-κB inflammatory pathways. Astragalus An adaptogen and tonic indicated for debility and CFS. Astragalus Regulatory effect on immune function; supports aspects membranaceus of innate immunity while promoting Th1 / Th2 balance. 2.5‒3.5 g dry herb Reduces abnormal cytokine production. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Hechtman & Naik, 2012) 62  Dr Sarah Myhill’s Approach to: CFS and ME CFS and ME are not diagnoses — they are clinical pictures. The role of healthcare practitioners is to identify the underlying mechanisms and contributing factors. Both are characterised by fatigue but in ME there is also an inflammatory process: ‒ CFS = poor energy delivery mechanisms. ‒ ME = CFS plus inflammation. Inflammation occurs when the immune system is active i.e., chronic infection, allergy and / or autoimmunity. Poor energy delivery systems can result in myriad symptoms. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 63  CFS and ME Chronic stress effectively ‘kicks’ mitochondria unrelentingly but: Eventually mitochondria will fatigue either because they run out of raw materials and / or there is no proper ‘shut down’ during sleep for healing and repair. If they become unable to respond to the unrelenting adrenaline kick, it results in the clinical picture of chronic fatigue syndrome. If the immune system lacks energy, then it cannot deal with an infection efficiently so the infection may become chronic. The above mechanisms result in the clinical picture of myalgic encephalomyelitis. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 64  CFS and ME Effects of poor energy delivery: Poor energy Physical fatigue, poor stamina. delivery to the Post-exertional malaise (akin to over-training in athletes). body: Loss of muscle power — muscles heavily rely on ATP! Muscle pain — because of an early switch into anaerobic metabolism with production of lactic acid. Variable blurred vision — the ciliary body muscles required for focusing tire easily. Subnormal core temperature. Poor energy Mental fatigue with brain fog — the brain weighs 2% of delivery to body weight but consumes 20% of total energy. the brain: Light and noise intolerance. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 65  POTS = postural CFS and ME orthostatic tachycardia syndrome Effects of poor energy delivery (cont.): Mental symptoms Low mood. which inhibit Feeling stressed. energy Procrastination. expenditure: Poor energy Hypotension — in severe cases this manifests delivery to with orthostatic intolerance and POTS. the heart: Angina described as ‘atypical’ (from lactic acid). Poor energy Susceptibility to infection, delivery to the unable to run a good fever. immune system: Slow healing and repair. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 66  CFS and ME Mitochondrial disorders manifest in the short term with poor energy delivery mechanisms. These then result in a multiplicity of possible symptoms. But mitochondria are not the only players: Poor energy delivery mechanisms involve the following which can be described using the car analogy: – Diet (fuel). – Mitochondria (engine). – Thyroid (accelerator pedal). – Adrenals (gear box). © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 67  CFS and ME To improve energy delivery mechanisms, all aspects must be addressed. They must also be addressed in the correct order. 1. Fuel in the tank (paleo-ketogenic diet, basic package of nutritional supplements and good gut function). 2. Mitochondrial engine — servicing and repair (quality and quantity of sleep). 3. The control mechanisms: Thyroid accelerator pedal. Adrenal gear box. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 68  CFS and ME 1. Fuel in the tank — paleo-ketogenic diet (PK Diet): Mitochondria evolved to use ketones from fat and fibre for energy. Increases expression of energy-producing genes — energy output is increased. Decreases inflammatory end-products and the toxic load on the mitochondria. “Let fat be thy medicine and medicine be thy fat!” Dr Gabriella Segura, consultant cardiologist. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 69  CFS and ME 1. Fuel in the tank — PK diet (cont.): Avoid gluten and all dairy except butter (almost 100% fat). Gluten — Non-coeliac wheat sensitivity (NCWS), identified in a subset of individuals with CFS / ME, is linked with increased intestinal permeability and systemic immune activation. Other grains are permitted so long as ketosis is maintained — this is why a ketone breath meter is so helpful. Dairy — at least 30% of people are allergic; lactose may be fermented; milk protein contains growth promoters (risk for cancer); high Ca / Mg ratio which induces Mg deficiency, increased risk of osteoporosis; milk protein increases blood viscosity. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Uhde et al. 2019) 70  CFS and ME How to determine you are in ketosis — three types of ketones: Beta-hydroxybutyric acid — is present in the blood and can be measured in the blood — this is the most accurate measure, but testing strips are expensive. Acetoacetate — is excreted in the urine. Testing is cheap and easy with urine keto-stix but as the body becomes more efficient at matching ketone production to demand, urine tests may show false negatives. Acetone Acetone — is exhaled and can be measured with breath testing. This can easily be tested after every meal to ensure you have not overdone the carbohydrates. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Uhde et al. 2019) 71  ppm = parts CFS and ME per million How to determine you are in ketosis (cont.): When sufficiently low in carbs, expect to blow 2–6 (ppm) of ketones. However, the body will always use sugar in preference to ketones. So ANY amount of ketones in the breath means you are in ketosis. Very high ketones (up to 10 ppm) may occur because: When stressed, an outpouring of adrenaline stimulates fat burning. Fasting — even on a PK diet you consume some carbohydrates! With fasting you get ALL your calories from fat, so ketones are higher. This illustrates the point that even in mild ketosis you will be using some sugars as a fuel — that is fine! Over-dosing with thyroid hormones may cause high levels. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. (Uhde et al. 2019) 72  CFS and ME How to determine you are in ketosis — false positives: The mechanism used to measure ketones is the same as that for measuring alcohol. You may see a positive if you have consumed any alcohol in the past 24 hours (depending on how much!) If you have SIBO, this too produces alcohol. Any products containing alcohol may give a positive result e.g., an alcohol wipe to clean the mouthpiece. The meter measures parts per million — it is very sensitive! Only a tiny amount of contaminant can upset the result. Many household cleaners contain volatile organic compounds which may register on the meter! (Uhde et al. 2019) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 73  CFS and ME How to determine you are in ketosis — false negatives: Eating or drinking anything other than water in the preceding 20 minutes may affect the test e.g., a sip of coffee can = a negative reading. Breath ketone levels may not align with blood levels and urine ketones, which does not matter. It is not unusual to see ketones present on a breath test, but the urine test is negative. With time, the body gets better at matching energy demands to delivery, so less ketones are ‘wasted’ through urinary losses. Note — being in ketosis is NOT dangerous and is not the same as ketoacidosis. (Uhde et al. 2019) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 74  CFS and ME 2. Mitochondrial engine — raw materials that mitochondria need daily for enzyme systems to work: CoQ10 100‒300 mg. Magnesium 300 mg (absorption enhanced by vit. D 10,000iu / day). Niacinamide 1500 mg daily. Acetyl L-carnitine 500‒2,000 mg (vegetarians and vegans are often deficient). Vitamin B12 1‒5 mg daily. D-ribose 5‒15 g daily — but has to be part of the PK diet carb count — it is a sugar! Use as a rescue remedy to shorten recovery time if the patient has overdone his / her activity. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 75  CFS and ME Factors that inhibit mitochondrial function: Problem: Remedy: Lactic acid Pace activity carefully. Products of the ‘fermenting gut’. PK diet. Vitamin C to bowel tolerance. Diamino compounds e.g., hair dye. Avoid. Malondialdehdye — a result of Improve antioxidant status esp. with poor antioxidant status. vitamin B12 and C to bowel tolerance. Parabens, polybrominated Avoid and eliminate, e.g., with heating biphenyls (e.g., in fire retardants), regimes such as with saunas. pesticides, mercury and other toxic Detoxify with multi-minerals and metals. glutathione 250 mg daily. Mycotoxins and viral proteins. Look for infectious cause. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 76  CFS and ME 3. The control mechanisms — balance the thyroid (accelerator pedal) and adrenal glands (gear box). The thyroid and adrenal glands allow energy delivery to be matched closely with energy demands. They are also essential for circadian rhythms. Tests of thyroid function are essential for two reasons: First to exclude an overactive thyroid. Secondly to see if there is a need for thyroid support, e.g., a trial of thyroid glandulars. It is also useful to do an adrenal stress profile. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 77  CFS and ME 3. The control mechanisms (cont.): The thyroid, adrenals and circadian rhythm: Light (sunshine is best) switches off melatonin production. Darkness triggers melatonin production from the suprachiasmatic nuclei in the pineal gland, following signalling from the retina. As melatonin rises TSH production is stimulated — spiking at 12am. The thyroid gland increases output of T4 which spikes at 4am.T4 is converted to T3 which spikes at 5am.T3 stimulates the adrenals and so adrenal hormones, including cortisol and DHEA, spike at 6‒7am; this wakes you up. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 78  CFS and ME ‘Fine tuning’: The combined effects of the fuel in the tank, the mitochondrial engines, the thyroid accelerator pedal and the adrenal gear box are reflected by our core temperature. Assuming the fuel and engines are correct: The average core temperature reflects thyroid function. The fluctuations reflect adrenal function. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 79  CFS and ME Correcting temperatures — adrenals: See earlier adrenal support. Or glandulars, e.g.: If the core temperature wobbles by more than 0.6 degrees (i.e., 0.3 above and below average) adrenal glandulars may be needed. Alternatively, adrenal herbs / nutrients can be implemented here. Start with a glandular such as adrenavive II (cortex only) on rising. Increase by one capsule every two weeks. Monitor with core temps and ‘how do you feel’. Most need adrenavive II 2‒6 daily (or adrenavive II 1‒3 daily). With time, some further benefit from adrenavive I (whole adrenal — cortex and medulla). © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 80  Review Nutrition 2, Endocrine Health for more CFS and ME info on thyroid support Correcting temperatures — thyroid: See thyroid support in endocrine lecture. Or glandulars, e.g.: If the average temperature is low, a thyroid glandular such as metavive may be needed. This comes in two sizes, I and II. Start with metavive I on rising. Monitor pulse, BP temperature and ‘how do you feel’. Increase by one capsule every two weeks, (take on rising and midday). Most end up on metavive I x 2—6 capsules daily (equivalent to metavive II x 1—3 capsules) daily. If temperature continues to be difficult, consider chronic infection. (Myhill et al. 2013) © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 81  Case Study: Exercise Andrea, 35 years, full-time cleaner, 1 daughter (aged 4). Presenting symptoms: Brain fog, fatigue, low mood muscle aches. Onset: Gradual from the age of 27 after a miscarriage and stressful period in her last relationship. Medical history: Suspected glandular fever aged 18. Diet: High ‘white carbohydrate’ intake throughout the day. Snacks on oat cakes and chocolate every afternoon. High dairy intake, no fish, frequently eats processed meats in sandwiches. 3 coffees most days to provide energy. 1 bottle of white wine per weekend. Medications: Paracetamol and ibuprofen every day for pain. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 82  Case Study: Exercise Andrea’s test results: 22 After reviewing these results, produce a naturopathic plan for Andrea. Also mention any further tests that may be beneficial if applicable. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 83  References Adam, TC. Hasson, RE. Ventura, EE. Toledo-Corral, C. et al. (2010). ‘Cortisol is negatively associated with insulin sensitivity in overweight Latino youth’. The Journal of clinical endocrinology and metabolism. 95(10). 4729–4735. Alimujiang, A. Wiensch, A. Boss, J. et al. (2019). ‘Association Between Life Purpose and Mortality Among US Adults Older Than 50 Years’. JAMA Netw Open. 2(5). e194270. Anderson, DC. (2008). ‘Assessment and Nutraceutical Management of Stress-induced Adrenal Dysfunction’. Integrative Medicine. 7(5). Bone, K. & Mills, S. (2013). Principles and Practice of Phytotherapy, 2nd edition. Chruchill Livingstone Elsevier. Boyle, NB. Lawton, C. Dye, L. (2017). ‘The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review’. Nutrients. 9(5). 429. Brown, BI. (2017). ‘Nutritional Management of Metabolic Endotoxemia: A Clinical Review’. Alternative Therapies in Health & Medicine. (4).42-54. Cases, J. Ibarra, A. Feuillère, N. Roller, M. & Sukkar, SG. (2011). ‘Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances’. Mediterranean journal of nutrition and metabolism. 4(3). 211–218. Ciaramella, A. Poli, P. Maccheroni, M. (2016). ‘F Somatisation and function of HPA in fibromyalgia: an investigation using sham and true pain stimuli’. Med Res Innov. 3. Deroon-Cassini, TA. Stollenwerk, TM. Beatka, M. Hillard, CJ. (2020). ‘Meet Your Stress Management Professionals: The Endocannabinoids’. Trends in Molecular Medicine. 26(10). 953-968. Dhabhar, FS. (2014). ‘Effects of stress on immune function: the good, the bad, and the beautiful’. Immunol Res. 58(2-3). 193-210. Fidyt, K. Fiedorowicz, A. Strządała, L. & Szumny, A. (2016). ‘β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties’. Cancer medicine. 5(10). 3007–3017. Filler, K. Lyon, D. Bennett, J. McCain, N. et al. (2014). ‘Association of mitochondrial dysfunction and fatigue: A review of the literature’. BBA Clin. 1. 12-23. Geer, EB. Islam, J. & Buettner, C. (2014). ‘Mechanisms of glucocorticoid-induced insulin resistance: focus on adipose tissue function and lipid metabolism’. Endocrinology and metabolism clinics of North America. 43(1). 75–102. Gerő, D. Torregrossa, R. Perry, A. Waters, A. et al. (2016). ‘The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro’. Pharmacol Res. 113. 186-198. Gibbert, J. Kreimendahl, F. Lebert, J. Rychlik, R. et al. (2017). ‘Improvement of Stress Resistance and Quality of Life of Adults with Nervous Restlessness after Treatment with a Passion Flower Dry Extract’. Complementary Medicine Research. 24. Hannibal, KE. & Bishop, MD. (2014). ‘Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation’. Physical therapy. 94(12). 1816–1825. Haß, U. Herpich, C. & Norman, K. (2019). ‘Anti-Inflammatory Diets and Fatigue’. Nutrients. 11(10). 2315. Hechtman, L. & Gruner, T. (2012). ‘The Endocrine System’ in L. Hechtman (Ed.), Clinical Naturopathic Medicine (pp. 1111-1124). Chatswood, NSW, Churchill Livingstone Elsevier. Hechtman, L. & Naik, S. (2012). ‘The Nervous System’ in L. Hechtman (Ed.), Clinical Naturopathic Medicine (pp. 1182-1200). Chatswood, NSW, Churchill Livingstone Elsevier. Hellhammer, J. Vogt, D. Franz, N. Freitas, U. & Rutenberg, D. (2014). ‘A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal- axis in chronically stressed male subjects: a randomized, placebo-controlled study’. Lipids in health and disease. 13. 121. Ishida, R. & Okada, M. (2006 ). ‘Effects of a firm purpose in life on anxiety and sympathetic nervous activity caused by emotional stress: assessment by psycho-physiological method’. Stress and Health. 22. 275–281. Jackson, E. (2013). ‘Stress relief’. ACSM’s Health & Fitness Journal. 17(3). Jansma, J. Brinkman, F. Hemert, SV. Aidy, SE. (2021). ‘Targeting the endocannabinoid system with microbial interventions to improve gut integrity’. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 106. 110169. Kirkland, AE. Sarlo, GL. & Holton, KF. (2018). ‘The Role of Magnesium in Neurological Disorders’. Nutrients. 10(6). 730. Konturek, PC. Brzozowski, T. Konturek, SJ. (2011). ‘Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options’. Journal of Physiology & Pharmacology. 62(6). Retrieved from http://www.jpp.krakow.pl/journal/archive/12_11/pdf/591_12_11_article.pdf Lee, JS. Kim, HG. Lee, DS. & Son, CG. (2018). ‘Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue’. Scientific reports. 8(1). 12890. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 84  References Lewis, JE. Tiozzo, E. Melillo, AB. Leonard, S. et al. (2013). ‘The effect of methylated vitamin B complex on depressive and anxiety symptoms and quality of life in adults with depression’. ISRN psychiatry. 2013. 621453. Maes, M. Ringel, K. Kubera, M. Anderson, G. et al. (2013). ‘In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation’. J Affect Disord. 150(2). 223-30. Mao, JJ. Xie, SX. Keefe, JR. Soeller, I. et al. (2016). ‘Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial’. Phytomedicine : international journal of phytotherapy and phytopharmacology. 23(14). Moritz, B. Schmitz, AE. Rodrigues, ALS. Dafre, AL. et al. (2020). ‘The role of vitamin C in stress-related disorders’. The Journal of Nutritional Biochemistry. 85. McPartland, JM. Guy, GW. & Di Marzo, V. (2014). ‘Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system’. PloS one. 9(3). e89566. Miller, VJ. Villamena, FA. & Volek, JS. (2018). ‘Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health’. Journal of nutrition and metabolism. 2018. 5157645. Mukai, T. Kishi, T. Matsuda, Y. Iwata, N. (2014). ‘A meta-analysis of inositol for depression and anxiety disorders’. Hum Psychopharmacol. 29(1).55-63. Myhill, S. Booth, NE. & McLaren-Howard, J. (2013). ‘Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit’. Int J Clin Exp Med. 6(1). 1-15. Nagy-Szakal, D. Williams, BL. Mishra, N. Che, X. et al. (2017). ‘Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome’. Microbiome. 5(1). Newberry, F. Hsieh, SY. Wileman, T. & Carding, SR. (2018). ‘Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?’. Clinical science.132(5). 523–542. Nicolson GL. (2014). ‘Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements’. Integrative medicine. 13(4). 35–43. Noda, M. Ifuku, M. Hossain, MS. & Katafuchi, T. (2018). ‘Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue Syndrome’. Frontiers in psychiatry. 9. 589. Pizzorno, J. (2014). ‘Mitochondria-Fundamental to Life and Health’. Integrative medicine. 13(2). 8–15. Pouteau, E. Kabir-Ahmadi, M. Noah, L. Mazur, A. et al. (2018). ‘Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial’. PloS one. 13(12). e0208454. Rehm, S. Sachau, J. Hellriegel, J. Forstenpointner, J. (2021). ‘Pain matters for central sensitization: sensory and psychological parameters in patients with fibromyalgia syndrome’. Pain reports. 6(1). e901. Rogers, GB. Keating, DJ. Young, RL. Wong, ML. et al. (2016). ‘From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways’. Molecular Psychiatry. 21(6). Sartori, SB. Whittle, N. Hetzenauer, A. Singewald, N. (2012). ‘Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment’. Neuropharmacology. 62(1). 304-312. Sripada, R. Marx, C. King, A. et al. (2013). ‘DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli’. Neuropsychopharmacol. 38. Uhde, M. Indart, AC. Yu, XB. Jang, SS. et al. (2019). ‘Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome’. Gut. 68(2). 377–378. © CNM: Nutrition 2: Stress and Fatigue. SM / DC. 85