Musculoskeletal Health PDF - Naturopathic Nutrition Year 2

Naturopathic Nutrition Year 2 Musculoskeletal Health 1 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Learning Outcomes In this lecture, you will learn about: Arthritis. Osteoarthritis. Rheumatoid arthr...

Naturopathic Nutrition Year 2 Musculoskeletal Health 1 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Learning Outcomes In this lecture, you will learn about: Arthritis. Osteoarthritis. Rheumatoid arthritis. Gout. Fibromyalgia. Back pain. Ankylosing spondylitis. Osteoporosis. 2 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Arthritis = from Greek Arthritis arthro-, meaning ‘joint’, and - itis, meaning ‘inflammation’. Arthritis = joint inflammation with pain. It includes over 100 conditions that affect joints, with some of the most common being: Osteoarthritis ― degeneration of the articular cartilage. ‘Wear and tear’. Rheumatoid arthritis ― autoimmune disease of synovial joints. Gout ― uric acid crystal deposition in joints. Ankylosing spondylitis ― autoimmune disease affecting the spine. Psoriatic arthritis ― autoimmune joint disease associated with psoriasis. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 3  Osteoarthritis Osteoarthritis (OA) = degenerative arthritis of the articular cartilage, typically affecting the weight-bearing (larger) joints and seen mostly over the age of 45 years. Signs and symptoms: Joint pain (e.g., knee, hip) with a gradual onset unilaterally. Often worsened by activity and relieved by rest. Associated joint stiffness. Joint swelling, deformity (due to osteophytes), crepitus. Heberden’s nodes: Swelling at the distal interphalangeal joints. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 4  extracellular matrix (ECM) Osteoarthritis = a non-cellular component of connective tissue Articular cartilage composition = extracellular matrix (water, collagen, proteoglycans) and chondrocytes. Collagen Matrix The normal turnover of matrix components is mediated by chondrocytes, which synthesise ECM components and the proteolytic enzymes responsible for their breakdown. Proteoglycans are formed of glycosaminoglycan (GAG) chains such as chondroitin sulphate, which is bound to hyaluronic acid. This provides osmotic properties ― critical to resist compressive forces. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 5  Osteoarthritis Pathophysiology: Proteolytic breakdown of cartilage matrix begins. Matrix metalloproteases (MMP) 1 such as collagenase degrade the ECM, releasing fragments into synovial fluid  release of pro-inflammatory mediators (e.g., IL-1β, TNF-α). The level of proteoglycans continues to drop, causing the cartilage to soften, 2 thin and lose elasticity, further compromising joint surface integrity. Fibrillations (vertical clefts) develop along the normally smooth articular cartilage. Over time, the loss of cartilage results in loss of joint space. 3 Erosion of the damaged cartilage in an osteoarthritic joint progresses until the underlying bone is exposed. 4 Subchondral bone responds with vascular invasion and increased cellularity. Bone thickening (‘eburnation’) and osteophyte (bone spur) formation occurs. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Martel-Pelletier, 2004) (Lorzada, 2018) 6  Chondrosenescence = Osteoarthritis age-dependent deterioration of chondrocyte function Causes / risk factors: Increasing age ― age-related loss of chondrocyte function is characterised by erosion of chondrocyte telomere length and mitochondrial dysfunction due to oxidative damage. Also associated with ‘inflammaging’. Previous joint trauma ― associated with joint inflammation and the onset of cartilage degradation. Overweight / obesity ― direct effect of mechanical load on cartilage. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Punzi et al. 2016; Rezuș et al. 2019) 7  Osteoarthritis Causes / risk factors (cont.): T2DM ― insulin stimulates chondrocytes to synthesise proteoglycans. Consider IR. Genetics ― the number of OA genetic risk loci are becoming increasingly identified. Drivers of chronic inflammation (immune lecture), e.g., metabolic endotoxaemia. Other joint diseases ― e.g., gout, RA. Nutritional deficiencies ― e.g., vitamin D; prevents articular cartilage erosion by regulating collagen II turnover and bone metabolism. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Osiecki, 2008; Lorzada, 2018; ) 8  Osteoarthritis Radiography: Key x-ray findings include joint-space narrowing, osteophytes and subchondral sclerosis. However, there is a lack of correlation between severity as determined by a radiograph and the degree of pain. In some cases, the joint appears normal with little, if any, joint space narrowing, yet the pain can be excruciating, and vice versa. Main conventional medications (NSAIDs): NSAIDs suppress symptoms, providing short-term relief. However, they have been shown to inhibit collagen matrix synthesis and accelerate cartilage breakdown, increasing the rate of degeneration. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 9  Osteoarthritis Natural approach: CNM Naturopathic Diet with a focus on supporting an anti-inflammatory environment (see immune health) and sufficient level of hydration for synovial support. Address the cause/s ― e.g., manage weight and improve insulin sensitivity (see obesity, energy metabolism, endocrine health), address dysbiosis / intestinal permeability (e.g., 5R protocol). Change dietary fats and oils ― decrease arachidonic acid as it’s a precursor to the inflammatory PGE2 series. Instead, increase dihomo-gamma-linolenic acid (DGLA) ― precursor to PGE1 series and eicosapentaenoic acid (EPA) ― precursor to PGE3 series. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 10  Osteoarthritis Natural approach (cont.): Nutrients: Functions: Glucosamine Used for GAG and hence proteoglycan synthesis, whilst sulphate also stimulating chondrocyte production of collagen. 500 mg x 3 daily A provider of sulphate ions for the synthesis of the chondroitin sulphate. Inhibits: MMPs (e.g., collagenase) ― reducing cartilage degradation; COX-2, PGE2 and downregulates NF-kB in chondrocytes. Chondroitin Chondroitin increases the amount of hyaluronic acid sulphate in joints ― keeping synovial joints lubricated. 200–400 mg / day Inhibits many cartilage-degrading enzymes. (James & Uhl, 2001; Singh et al. 2015) 11 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Osteoarthritis Natural approach (cont.): Nutrients: Functions: Methylsulfonyl- Anti-inflammatory effects, likely through methane (MSM) NF-κB inhibition and free radical scavenging. 1 g / day, building Stimulates proteoglycan and hyaluronic acid to 3–4 g / day synthesis; inhibits proteolytic enzymes. Vitamin C Anabolic effect on cartilage; required for 1–5000 mg / day chondrocyte protein synthesis (e.g., collagen). Antioxidant properties reduce impact of ROS on genomic stability in chondrocytes. Vitamin E Synergistic with vitamin C. Antioxidant, inhibits 200–400 IU / day lysosomal enzymes, increases proteoglycan deposition. 12 (Jomphe et al. 2007; Monfort et al. 2007; Nakhostin-Roohi © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. et al. 2011; Chaganti et al. 2014; Dunlap et al. 2021)  Osteoarthritis Natural approach (cont.): Nutrients: Functions: Vitamin D Prevents articular cartilage erosion by regulating 2000–10,000 iu collagen II turnover and bone metabolism. depending on Several studies have shown low serum vitamin D to be tested levels associated with an increased risk for progression of OA. Tart cherry Rich in anthocyanins and other flavonoids. Up to 3000 mg / Anti-inflammatory: Shown to inhibit COX, inhibit day extract NF-κB and reduce IL-6. Antioxidant effects. Shown to reduce pain and hsCRP levels in knee OA. Vitamin K2 Vitamin K binds to vitamin K-dependent proteins in 50–100 mcg joints. This binding inhibits cartilage calcification. (Kirakosyan et al. 2008; Schumacher et al. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 2013; Chin et al. 2015) 13  Consider Osteoarthritis Golden Mylk! Natural approach ― anti-inflammatory herbs: : Herb: Functions: Turmeric Curcuminoids inhibit NF-κB activation and pro- 500–2000 mg inflammatory cytokines like IL-1β and −6. Boswellia Boswellic acids inhibit 5-Lipoxygenase activity and 300 mg x 3 daily hence leukotriene B4 formation. Inhibits MMP release. Devil’s Claw The harpagosides in Devil’s Claw 100–1000 mg per can reduce the production of day split dose — inflammatory cytokines including building gradually IL-6, IL-1β and TNF-α. Ginger Inhibits TNF-α and PGE2 through inhibition of 500–1000 mg COX-2 and reduces inflammatory joint pain. (Ghasemian et al. 2016; Rondaneilli et al. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 2020 ; Kloesch et al. 2013; Yu et al. 2020) 14  Osteoarthritis Natural approach (cont.): Hydrotherapy ― contrast showers (starting with heat, ending with cold, and with heat being 3–4 x longer than cold) to areas of pain. Epsom salt baths (500g–1kg). Tissue salts (1 each x 3 daily): - Ferrum phos ― for inflammation and pain that comes with advanced OA. This causes both intra and extracapsular hyperacidity which further perpetuates the degeneration. - Calc. phos and calc. fluor ― for reduction of joint degeneration. - Nat. phos ― helps to alkalise the intra and extracapsular fluid. Referral to other modalities e.g., acupuncture, osteopathy. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 15  Osteoarthritis Natural approach (cont.): Exercise ― low-moderate intensity. Swimming, and practices such as yoga, Tai Chi and Pilates all increase joint circulation and strengthen surrounding muscles. Topical application (use twice daily): Devil’s Claw or MSM can be used topically. Warming oil blend, e.g., rosemary, ginger, cayenne (used cautiously) to encourage vasodilation / blood flow. Essential oils, e.g., peppermint, wintergreen, frankincense, basil. Add drops into a carrier oil or cream. Anti-inflammatory, blood circulation promoting and muscle relaxing effects. 16 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Mohammadifar et al. 2021)  Rheumatoid Arthritis Rheumatoid arthritis (RA) = a chronic inflammatory autoimmune disease characterised by synovial joint inflammation, potentially affecting all organs except the brain. Signs and symptoms: Symmetrical polyarthritis ― affecting small distal joints of the hands / feet. Can affect more proximal joints. Hand deformities (e.g., swan neck). Subcutaneous nodules. Complications: C1/2 vertebral subluxation, pleurisy, pulmonary fibrosis, kidney disease, Sjögren’s syndrome, carpal tunnel syndrome. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Pratt & Isaacs, 2014) 17  APCs = Antigen Rheumatoid Arthritis Presenting Cells RANKL = Receptor activator of nuclear factor kappa-Β ligand Pathophysiology: (a transmembrane protein) ― regulates osteoclast activity Citrullination occurs (conversion of arginine to citrulline), which is mediated by 1 genetics and environmental factors (see next slides). APCs recognise citrulline- containing regions of several proteins (e.g., type II collagen, fibrin) as foreign. APCs present the antigens to CD4+ T cells, triggering T-cell 2 differentiation. B-cells are activated  plasma cells  autoantibodies (anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor). T-cells stimulate macrophages in synovial joints to produce 3 inflammatory cytokines (e.g., TNF-a, IL-1, IL-6). The inflammatory cytokines stimulate fibroblast-like synoviocytes (FLS), which 4 release proteases ( cartilage degradation) and together with the cytokines increase RANKL expression ( increasing osteoclasts and bone destruction). (Makrygiannakis et al. 2008; Wegner et al, 2010; © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. Derksen et al, 2017; López-Mejías et al. 2019) 18  PTPN22 = protein Rheumatoid Arthritis tyrosine phosphatase non-receptor 22 Causes / risk factors: Genetics: – HLA-DRB1 alleles constitute the largest genetic risk factor for RA, estimated to contribute at least 30% of the total genetic component of this disease. – PTPN22 SNP – the largest non-HLA genetic association in RA. Associated with multiple autoimmune diseases. Smoking ― a significant RA risk factor. Associated with oxidative damage; raised pro-inflammatory cytokines (e.g., IL-17); increased MMP expression; epigenetic changes. (Change et al. 2014; Yarwood et al. 2016; Dedmon, 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 19  Rheumatoid Arthritis Causes / risk factors (cont.): Porphyromonas gingivalis (periodontitis) ― produces the enzyme peptidylarginine deiminase (PAD), which induces citrullination. Citrullinated proteins are key targets of autoantibodies in RA. Silica dust exposure ― increases inflammatory cytokines (e.g., TNF- α) and MMP activity. Other infectious agents, e.g., EBV, Proteus mirabilis (often UTIs). (Blaschke et al. 2000; Mikuls et al. 2012; Gómez- Bañuelos et al. 2019; Lopez-Olivia, & Bartold, 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 20  Rheumatoid Arthritis Causes / risk factors (cont.): Intestinal dysbiosis: ‒ Prevotella copri is often abundant in RA (even in preclinical stages) and can induce Th17-related cytokines. ‒ Raised Collinsella abundance is associated with RA; increasing gut permeability and IL-17. ‒ Reduced Bacteroides spp. and Bifidobacterium spp. abundance. ‒ Many RA patients have positive SIBO breath test. Links with disturbed gut barrier function (e.g.,  metabolic endotoxaemia) and intestinal inflammation. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Maeda et al. 2019; Shang et al. 2019) 21  Refer to the ANP Rheumatoid Arthritis interactions database Blood test findings: Raised inflammatory markers (ESR / CRP). Rheumatoid factor (RF) in 70% of cases ― an IgM antibody that targets the constant region of IgG antibodies. Anti-citrullinated protein antibodies (ACPAs) ― can be present in the serum up to 10 years before the onset of clinical symptoms. Conventional treatment: DMARDs (e.g., methotrexate), NSAIDs, corticosteroids, biologics (e.g., infliximab). Treatment response is highly variable, and often includes a variety of side effects. (NICE, 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 22  Rheumatoid Arthritis Natural approach: CNM Naturopathic Diet with a focus on reducing inflammation (e.g., no refined sugar, trans fats, dairy, limited red meat; high omega-3, etc.). Abundant antioxidants (rainbow diet) ― RA sufferers typically have low serum levels of antioxidants, and high levels of oxidative stress, which can contribute to tissue damage. See the autoimmune protocol (AIP) ― immune health lecture. Gluten-free ― as gluten is a key food source of molecular mimicry and inducer of intestinal permeability (triggering zonulin release). (Fasano , 2012; Mateen et al. 2016; Fasano, 2020; Tajik et al. 2020; Bruzzese et al. 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 23  Consider testing Rheumatoid Arthritis where applicable, e.g., oral microbiome Natural approach ― address the cause, e.g.: Oral microbiome (see assessment / diagnostics lecture) – – Anti-microbials and biofilm disruptors e.g., silver nanoparticle liquid (e.g., 1 tbsp in water as a mouthwash). Ginger, turmeric, aloe vera, clove, garlic and neem have demonstrated anti-microbial effects against P. gingivalis. – Oral probiotic and immune support (e.g., vitamin C). Stop smoking; stress management (see stress lecture). Gut barrier and microbiome support (see GI health lecture). EBV ― immune support (see immune lecture); anti-virals, e.g., L-Lysine, berberine, resveratrol, turmeric, EGCG. (Kadam et al. 2020; Natto, 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 24  See immune lecture Rheumatoid Arthritis – autoimmunity for more therapeutics Natural approach (cont.): Nutrients: Functions: Vitamin D A potent inhibitor of Th17 pathogenicity Test and and promotes Treg differentiation. optimise levels Shown to lower the levels of RANKL. Omega-3 Anti-inflammatory effects, beneficial in RA: 1 g+ of actual Reduce Th17 cells and IL-17 levels. EPA Inhibit PGE2, NFκB, TNF-α and Interleukin-6. GLA Shown to reduce pain, stiffness and swelling in RA. Borage oil 1–2 g Converted to DGLA, which forms daily the anti-inflammatory PGE1. It inhibits 5-LOX and reduces NF-kB activity. (Reed et al. 2014; Guan et al. 2020; Kostoglou-Athanassiou et al. 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 25  Rheumatoid Arthritis Natural approach (cont.): Nutrients: Functions: Resveratrol A polyphenol that reduces 200 mg / day Th17 cells; downregulates NF-KB and COX-2. Alpha lipoic acid Potent fat- and water-soluble antioxidant, raising Up to 1200 mg / day intracellular glutathione. Anti-inflammatory ― shown to downregulate NFκB and reduce inflammatory markers such as CRP. EGCG Anti-inflammatory — inhibits NF-κB, inducible nitric 2–3 green oxide (iNOS) and COX-2. tea / day Shown to induce apoptosis of FLS and osteoclasts. (Akbari et al. 2018; Yang et al. 2018; Lee et al. 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 26  Rheumatoid Arthritis Natural approach (cont.): Nutrients: Functions: Quercetin Anti-inflammatory: Inhibits NF-kβ and 1.5–3 g / day COX-2, as well as various inflammatory cytokines e.g., IL-17, TNF-α. Shown to inhibit the invasion of FLSs. Zinc (e.g. citrate) Deficiency / insufficiency is 15–30 mg / day common in RA, which can predispose to inflammation. Delta-6-desaturase activity decreases. Low levels are associated with increased: NF-kb activation, CRP, IL-1β, and TNF-α. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Yuan et al. 2020; Shen et al. 2021) 27  Rheumatoid Arthritis Natural approach (cont.): Probiotics ― e.g., Lactobacillus casei currently has the strongest evidence for use in RA (minimum of 108 CFU / capsule per day). It ↓inflammatory cytokines such as TNF and Il-6. L. rhamnosus GG also appears to be effective. Anti-inflammatory herbs: Turmeric, Devil’s Claw, boswellia and ginger (see OA). Tissue salts (2 pills x 3 daily): ‒ Ferrum phos ― ↓ inflammation and provides support if anaemic. ‒ Nat. phos ― an alkaliser for the body, esp. for synovial fluid. ‒ Calc. phos ― helps improve mineralisation and joint integrity. (Ammon, 2001; Kloesch et al. 2013; Ferro et al. 2021; Pourhabibi-Zarandi et al. 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 28  Case Study: Exercise Sue, 37 years, presents with RA (bilateral wrist / ankle pain). RA onset: 4 years ago. Had been caring for her ill father leading up to this. Felt generally “run down and exhausted” with a chronically sore throat around the time of the initial joint symptoms. Interventions: Took steroids and then methotrexate in the first year. Since then has managed pain with high dose naproxen and with dietary changes (having gone vegetarian and cut out gluten). Diet: 1 x coffee + cornflakes w. cow’s milk, processed meat alternatives, low veg / fruit, snacks often (biscuits), 800 ml water/day. Other symptoms: Bloating / flatulence for “many years”. BSC 5. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 29  Case Study: Exercise Relevant history: Recurrent tonsilitis as teenager with regular antibiotics. Glandular fever aged 19 (university). Cold sores 2 x per year since university. Smoked from age 17‒28 (approx. 5 per day). Recent testing: VCA IgG (EBV) positive. Stool: Low commensal diversity, high P. copri; Bifidobacterium spp. below detectable limits. Questions: 1. Outline potential triggers and mediators in this case. 2. Write therapeutic aims for Sue. 3. Outline dietary, supplement / herbal (incl. dosages) and lifestyle recommendations with justification. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 30  Gout Gout = arthritis due to deposition of monosodium urate (MSU) crystals within joints causing acute inflammation. Signs / symptoms: Monoarticular arthritis most commonly affecting the 1st metatarsophalangeal joint (big toe). Most often affecting men. Pain, swelling, redness and heat. Shiny skin. Can awaken patients from sleep. Can affect other joints (e.g., knee). Inability to use the joint during symptomatic episode Reaches its peak within 24 hours, often with fever and malaise. (Richette & Bardin, 2010) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 31  hyperuricaemia = Gout raised serum uric acid Pathophysiology: Hyperuricaemia is the key risk factor for gout and is a prerequisite for MSU crystal formation. Uric acid is the final breakdown product of purine metabolism. Purines Purines are part of the chemical structure Adenine Guanine of DNA and RNA found in all of the body’s cells, and in virtually all foods. Xanthine When cells die, the purines in the DNA Xanthine oxidase and RNA are released and recycled. Uric acid Metabolism of foods release purines. Interleukin-1β is the key cytokine mediating inflammation in gout. (Narang & Dalbeth, 2020) 32 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  AMP = adenosine Gout monophosphate Gout co-morbidities: Hyperuricaemia: Increases NF-kβ, disrupts eNOS activity, shows pro-oxidant effects, increases RAAS activity. Linked to hypertension, CVD, T2DM and kidney disease. Causes / risk factors ― uric acid overproduction: Dietary purines ― e.g., meat, organ meat, seafood (e.g., shellfish). High cell turnover disorders ― e.g., leukaemia, haemolytic anaemias, psoriasis. Chemotherapy ― increased cell death. Fructose (consider HFCS in soft drinks) ― increases ATP degradation to AMP, a uric acid precursor. (Bardin & Richette, 2017; Seong-Kyu, 2018; Marin & Maalouf, 2018; Pascart et al. 2018) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 33  AMP = adenosine Gout monophosphate Causes / risk factors ― underexcretion of uric acid: Medication side effects ― e.g., diuretics, aspirin (low dose) and ACE inhibitors increase urate renal retention. Renal insufficiency (CKD) ― impairs uric acid excretion. Alcohol (e.g., beer) ― decreases urate excretion and increases urate production. Genetics ― various SNPs in ABCG2 have been associated with gout. ABCG2 mediates urate secretion primarily in proximal renal tubule cells. Obesity and insulin resistance (IR) ― reduces urate renal excretion. Dehydration. (Neogi et al. 2014; Zhang et al. 2014; © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. Salem et al. 2017; Yu et al. 2017) 34  Gout Diagnosis: Mostly based on full clinical presentation. The presence of hyperuricaemia (>6.8 mg / dL) does not equate with a diagnosis of gout. Gold standard for diagnosis (although not practical) ― synovial joint microscopy showing urate crystals. Conventional medications: For ‘prevention’: Allopurinol ― inhibits xanthine oxidase (XO). For acute attacks: NSAIDs; colchicine ― which has a narrow therapeutic window and risk of toxicity. GIT side effects are especially common. (Bethesda, 2012) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 35  Gout Natural approach: CNM Naturopathic Diet with a focus on reducing uric acid levels: Avoid / minimise: Alcohol, fructose-containing beverages, pro-inflammatory foods (e.g., refined carbohydrates, trans fats). Low purine diet (see next slide). Address specific causes, e.g., IR (see endocrine lecture), weight loss strategies where appropriate (see obesity lecture). Optimise omega-3:6 ratio to reduce inflammation (see earlier). Minimum of 2L of water daily ― dilutes urine and promotes uric acid excretion. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 36  Gout Food Group Low Purine Moderate Purine High Purine 0‒50 mg / 100 g 50‒150 mg / 100 g 150‒1000 mg / 100 g Bread, Cereals White bread /pasta Barley, Wholegrain bread and pasta Grains corn, polenta couscous Wholegrain cereals, oats, brown rice. Fruit All fruit and fruit juices Vegetables Most vegetables except those Cauliflower, kale Chinese greens, in moderate / high group broccoli, spinach, asparagus, Brussel’s sprouts avocado, mushrooms Meat, Fish, Eggs Peanuts, cashews, groundnuts. Game: Pheasant, quail, Poultry and Nuts except those in moderate Most fish except those in high group. grouse, rabbit, venison Protein / high group (but beware salt Oysters, muscles, shrimp, prawns Organ meats: Pâté. products content in packaged nuts) Most red meats and sausages (veal, Fish roe. Meat and yeast beef, lamb, pork) except high group. extracts. Scallops, Poultry herring, trout, mackerel, Lentils, chickpeas and most beans crayfish, lobster, Soya ― tofu, tempeh, miso. anchovies, sardines. Dairy All cow, goat and sheep dairy Others Most cooking oils, olives, tea, Alcoholic beverages jams, chutney, pickles Gravies and stock mixes © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 37  Gout Natural approach (cont.): Protein intake should not be excessive (i.e., not >0.8 g / kg body weight), as this may accelerate uric acid synthesis. However, sufficient protein is needed because amino acids also decrease resorption of uric acid in the renal tubules. Avoid the feet getting cold ― uric acid is a highly water insoluble molecule which deposits easily in cold weather. Warmth helps dissolve uric acid crystals. Castor oil packs ― soak a flannel in warm castor oil, wring it out and place over the joint. Place hot water bottle on the cloth. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Pizzorno & Murray, 2007; Osiecki, 2008) 38  NLRP3 = a cellular protein that Gout detects products of damaged cells and triggers an immune response. Natural approach (cont.): Nutrients: Functions: Quercetin Actions that benefit hyperuricemia and gout include: 200‒400 XO inhibition and promoted activity of mg x 3 daily urate excretion transporters. Anti-inflammatory activity by targeting NLRP3 inflammasome-IL-1β pathway and TLR signalling. Antioxidant properties ― reducing inflammatory effects. EPA Has been shown to inhibit urate transporter 1 3 g daily (URAT1), thus increasing renal urate excretion. Anti-inflammatory: Inhibition of the PGE2 pathway; NFκB, TNF-α and interleukin-6. (Saito et al. 2020; Tumova et al. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 2021; Thanutchaporn, 2022) 39  Gout Natural approach (cont.): Nutrients: Functions: Methyl folate Shown to inhibit XO with its high 400‒800 mcg + affinity for the binding site for the high dietary folate enzyme’s cofactor, molybdenum. Tart cherry Its polyphenols (e.g., anthocyanins) have been Up to 3000 mg / primarily credited with tart cherry’s ability to: day extract Inhibit COX-1, COX-2, NFκB and IL-1β. Reduce uric acid levels, possibly through XO inhibition or increased renal clearance. Reduce oxidative stress. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Zhang et al. 2018; Collins et al. 2019) 40  Gout Natural approach (cont.): Herbs: Functions: Celery Reduces uric acid through inhibition of XO Apium activity, reduction in oxidative stress and graveolens inflammation (COX and LOX inhibiting). Actions are largely attributed to flavonoids (e.g., apigenin) and phenolic compounds. Dosage: Juice 1 celery daily. Or use seeds ― add 1 tbsp to 2 cups of water and boil until the seeds are soft. Nettle Diuretic and alkalising effects, associated Urtica with increasing urinary excretion of uric acid. dioica (leaf) Dosage: 1 tbsp infused in hot water for 10 mins x 2 daily. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Soliman et al. 2020) 41  Fibromyalgia Fibromyalgia (FM) = a condition of chronic widespread pain and abnormal pain-processing mechanisms. Other key symptoms: Fatigue, sleep disturbance, stiffness, headaches, bowel disturbances, anxiety and depression. American College of Rheumatology (2010) diagnostic criteria: 1. A widespread pain index (WPI) score of 7+ and a symptom severity scale (SS) score of 5+. Or you have a WPI score of 4–6 and a SS score of 9+. 2. Symptoms lasting at least three months at a similar level. 3. No other health problem that would explain the symptoms. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Wolfe et al. 2010) 42  It is crucial for us to consider Fibromyalgia WHY pain processing is faulty Causes / risk factors: Trauma ― physical (e.g., surgery, car accident) and emotional (e.g., bereavement, divorce, bullying). “Never been right since…” – Particular links with adversity in early life; excessively activating stress responses during development, thus altering responses to stimuli through hyperalgesic priming. This is associated with HPAA dysregulation. – Disrupted cortisol levels are common (also consider stress). Hypothyroidism ― thyroid hormones normally inhibit the synthesis and secretion of substance P in areas of the CNS such as the dorsal horn of the spinal cord. (Becker et al. 2012; Haliloglu et al. 2017; Gündüz et al. 2018; Zazour & Khalil, 2022) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 43  Review Nutrition 2, GI Fibromyalgia Health for SIBO causes Causes / risk factors ― intestinal dysbiosis: SIBO ― highly prevalent in FM. The degree of pain in FM correlates significantly with breath test hydrogen levels. Individuals with FM show significantly altered composition of SCFA-metabolising bacteria. Faecalibacterium prausnitzii and Bacteroides spp. were found in lower relative abundance in FM. Gut bacteria could modulate nociception (pain) at multiple levels, including direct effects on peripheral nociceptors to modulation of perception in the CNS. This is likely mediated by metabolites including SFCAs, bile acids and neurotransmitters. (Pimentel et al. 2004; Minerbi & Fitzcharles, 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 44  NMDA = N-methyl- Fibromyalgia D-aspartate Causes / risk factors (cont.): Infections ― e.g., EBV ― high EBV IgG concentrations in FM correlate with pain intensity and other key symptoms. Nutritional deficiencies: ‒ Vitamin D ― ↓ PGE2 synthesis, inflammatory cytokines and modulates central pain processing. ‒ Vitamin B12 ― enhances noradrenaline and 5-HT as inhibitory pain signals and supports myelination. ‒ Magnesium ― inhibits NMDA receptors, glutamate & substance P. Gluten reactivity ― in the form of coeliac disease, non-coeliac gluten sensitivity or allergy is common in FM. (Haliloglu et al. 2017; Giat et al. 2018; Haddad et al. 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 45  Fibromyalgia Causes / risk factors (cont.): Genetic SNPs affecting methylation and detoxification, e.g.: – MTHFR (C667T SNP) = impaired methylation (detoxification, NT production, e.g., serotonin). – COMT ― variations associated with low COMT activity are common in FM. Val158Met polymorphism plays a role in FM pain sensitivity (lowering the pain threshold). – GSTM1 (e.g., absent gene) ― increases the toxic burden. Heavy metals (e.g., mercury) ― ↓ glutathione, disturbs GABA-glutamate balance and methylation, ↑ pro-inflammatory cytokines. (Martinez-Jauand et al. 2013; Haley et al. 2014) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 46  Many aspects of FM Fibromyalgia overlap with those of CFS. Natural approach: Treat the cause! Follow dietary guidelines outlined for stress, mitochondrial dysfunction and CFS / ME in stress / fatigue lecture. Gluten-free diets and a low FODMAP diet have shown clinical improvements in FM. Support the thyroid, adrenals, GIT as needed. E.g., apply a SIBO / 5R protocol; support commensal microbial diversity and SCFA-producers with fibre, polyphenols etc. Reduce glutamate levels ― by increasing glutamate decarboxylase (GAD) co-factors (Mg, vitamin B6, Zn, vitamin C, taurine). Avoiding glutamate sources (e.g., MSG) and alcohol (inhibits GAD). (Isasi et al. 2014; Holton, 2016; Marum et al. 2017; Slim et al. 2017; Pagliai et al. 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 47  Fibromyalgia Natural approach (cont.): Nutrient: Functions: Magnesium Magnesium blocks NMDA receptor channels (as malate or and must be removed for excitation to occur. citrate) This leads to anti-nociceptive and analgesic effects. 200‒500 mg / Zinc is also an NMDA antagonist ― it is day co-released with glutamate into the synaptic cleft, and dampens the excitatory response. Vitamin D Modulates central pain processing, reduces Optimise levels inflammatory cytokines and PGE2. Vitamin B6 A co-factor for the glutamate decarboxylase ― 50–100 mg / day needed for the conversion of glutamate to GABA. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Holton, 2016; Ellis et al. 2018; Pagliai et al. 2020) 48  Also recommend Fibromyalgia tryptophan-rich foods Natural approach (cont.): Nutrient: Functions: Coenzyme CoQ10 deficiency is common in FM. The degree of Q10 deficiency appears to correlate with symptom severity. CoQ10 is a potent antioxidant and when deficient 300 mg daily can be associated with mitochondrial dysfunction. Plays a key role in the electron transport chain. 5-HTP Low levels of serotonin and L-tryptophan have been 100–300 mg observed in the cerebrospinal fluid of FM patients. daily 5-HTP is the direct precursor to serotonin, which plays a role in descending pain regulation. It also supports melatonin synthesis. (Hechtman, 2012; Abou-Raya et al. 2014; © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. Pagliai et al. 2020) 49  See Nutrition 1, Superfoods Fibromyalgia – heavy metal detox Natural approach ― detoxification and elimination: Reduce toxic load; support liver detoxification phases and elimination pathways (see detoxification lecture). Optimise levels of: ‒ Metallothionein (binds to heavy metals) ― requires adequate cysteine, zinc, copper, and selenium. ‒ Antioxidant enzyme status (e.g., SOD, glutathione peroxidase etc.) with selenium, zinc, etc. ‒ Chain-breaking antioxidants (vitamin C, E, flavonoids, carotenoids). Focus on a ‘rainbow’ diet. Optimise glutathione levels ― e.g., NAC, silymarin, resveratrol. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 50  balneotherapy = the Fibromyalgia practice of immersing a subject in mineral water Natural approach ― detoxification and elimination (cont.): Saunas ― increase the excretion of toxins incl. mercury. – A study of 44 FM patients doing 12 weeks of 1 sauna x 3 days / week (combined with underwater exercise) found that all subjects’ symptoms significantly improved. – Technique: High enough temperature to start sweating freely in 15–20 minutes. 20–40 min heavy sweating. Drink before and after (typically ~1 pint / 20 min moderate / heavy sweating. Hydrotherapy ― Epsom salts (0.5‒1 kg) with few drops of lavender essential oil in bath. Balneotherapy is well researched for FM. (Matsumoto et al. 2011; Sears et al. 2012; Cao et al. 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 51  Fibromyalgia Natural approach (cont.): Support methylation ― for NT synthesis and detoxification: folate, B12, B6, B2, choline, betaine (TMG, e.g., in beetroot) and zinc; SAMe. Consider methylated B vitamins. Sleep support ― FM patients demonstrate abnormal α-rhythms and wakefulness during non-REM sleep. Sleep is therefore non-restorative. Sleep deprivation impairs descending pain-inhibition pathways. ‒ See nervous system lecture for insomnia recommendations. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 52  Fibromyalgia Natural approach — herbal medicines: Herb: Functions: Ashwagandha Supports the HPAA and restorative sleep through (Withania somnifera) its influence on GABA. Anti-nociceptive effects 300‒600 mg 1-3 x / day likely mediated by the opioidergic system. St John’s wort Interacts with several neuronal (Hypericum perforatum) systems that modulate nociception. 600–1200 mg as 3 Affinity for GABA and MAO ― divided doses daily. ↑ serotonin / dopamine. Devil’s Claw Inhibits: Proinflammatory cytokine (Harpagophytum release (e.g., IL-1β, IL-6, TNF-α) procumbens) from macrophages; COX-2 3‒6 g daily dried herb expression and lipid peroxidation. (Panossian et al. 2010; Wang et al. 2010; Flodin et al. 2015) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 53  Fibromyalgia Natural approach (cont.): Capsaicin, a compound derived from cayenne, desensitises C-fibre sensory neurons that are responsible for the release of substance P. Regular aerobic exercise (e.g., walking, cycling, swimming) and Tai Chi can improve pain perception. Avoid high intensity. Stress support as appropriate. See stress / fatigue lecture. Consider adrenal testing / support. Tissue salts (2 pills x 3 daily): Kali. phos — ‘nerve nutrient’; Mag. phos — helps improve sleep, reduces restlessness, reduces headaches, anxiety and is the ‘pain reliever’. (Wang et al. 2010; Casanueva et al. 2013; Flodin et al. 2015; Bidonde et al. 2017) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 54  Back Pain Back pain = pain occurring anywhere in the back. This is most commonly lower back pain (LBP). The global prevalence of LBP is estimated to be about 8%. With up to 60% of adults expected to have LBP at some point in their life. There are numerous causes of back pain, and so initially categorising it can be helpful. Back pain can be broadly categorised as being mechanical or non-mechanical. Back pain can be acute or chronic (> 12 weeks). (Chenot et al. 2017; Wu et al. 2017) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 55  Back Pain Mechanical back pain: By far the most common category. Associated with movement. Structures often implicated include: - Muscles (e.g., muscle strains, spasms) — typically relieved by rest and heat. - Facet joints — often worse with spinal extension. Normally resolves in a short time period. - Intervertebral discs (e.g., degeneration, herniation) — if inflamed, this is often worsened by spinal flexion and coughing / sneezing. - Bones (e.g., vertebral fracture) — look for unremitting pain, trauma, osteoporosis risks / diagnosis. Referral necessary. (Chenot et al. 2017; Delitto et al. 2012) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 56  Back Pain Mechanical back pain — case history considerations: Pain onset: Gradual without trauma might indicate more of a degenerative picture or muscle fatigue. A sudden onset (e.g., trauma, waking with pain) is likely associated with acute inflammation. Age: Spinal joint degeneration begins from the age of about 30. Therefore, increasing age results in a higher chance of degenerative pain, and approximated vertebrae (facet joints). Disc herniations are common around the age of 30‒40 years. Daily If inflammation is a key feature, the pain is often pattern: relieved by movement. Morning stiffness is also common with inflammation. A muscular or degenerative issue often worsens through the day. (Chenot et al. 2017; Delitto et al. 2012) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 57  Back Pain Mechanical back pain — risk factors/causes: Physical trauma — e.g., sports injury, heavy lifting (more common in more manual occupations). Emotional stress — ↑ SNS activity = ↑ muscle tone / shortening. Chronic stress can also alter neurotransmitter levels associated with descending antinociceptive pathways. ‒ Studies have shown that chronic LBP is exacerbated by negative thoughts (‘catastrophising’), fear / pain avoidance. Inflammation — see immune health for chronic inflammation causes (e.g., poor diet, metabolic endotoxaemia, obesity). (Wessels et al. 2006; George et al. 2008; Delitto et al. 2012; Wippert & Wiebking, 2018) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 58  Back Pain Non-mechanical back pain: A smaller percentage of back pain is non-mechanical. Examples are: Systemic diseases (e.g., ankylosing spondylitis). Fibromyalgia. Endometriosis. Renal disease (e.g., infection / stones). Shingles. Malignancy — often secondary in the vertebral column from other sites. Osteomyelitis (bone infection). © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 59  Back Pain Natural approach: CNM Naturopathic Diet with a focus on reducing inflammation (e.g., no refined sugar, trans fats, dairy, limited red meat; high omega-3, etc.). Studies have highlighted the benefits of a Mediterranean diet in reducing MSK pain. Its antioxidant / anti-inflammatory actions are largely attributed to the polyphenol content. Address mediators of chronic inflammation as needed (e.g., gut protocol, sleep hygiene etc.) Address stress as needed (see stress lecture). (Pasdar et al. 2022) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 60  See immune lecture — Back Pain chronic inflammation for more therapeutics Natural approach (cont.): Nutrients: Functions: Magnesium Shown to block the NMDA-receptor 200‒400 mg channels, thus reducing nociception and neuropathic pain in chronic LBP. Also exerts muscle-relaxing actions. Omega-3 Fish oils have shown significant improvements in LBP. 1 g+ of EPA Anti-inflammatory, through inhibition of the PGE2 pathway. Inhibiting NFκB, TNF-α and Interleukin-6. Phosphatidyl- Provides neuronal cell membrane support, including serine myelination. Shown to be beneficial in chronic 200–400 mg neuropathic LBP, with apparent synergism with EPA. (Yousef, & Al-deeb, 2013; Ikuko et al. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 2022; Zhou et al. 2022) 61  Back Pain Natural approach (cont.): Nutrients: Functions: Proteolytic enzymes A study showed benefits of proteolytic enzymes with Serrapeptase LBP patients reporting improvements within 6 weeks. up to 75 mg Inhibits PGE2 synthesis. Reduces Bromelain pain mediators (e.g., bradykinin). up to 1500 mg Fibrinolytic — aiding fluid drainage. Bach Flowers E.g.: Vervain (overenthusiasm, intense — manifests 4 drops 4 times daily as 'stiffness'). Impatiens (impatient, can manifest as muscle tension). Mimulus (fear, slow to recover from injury, fear of movement). Star of Bethlehem (trauma, shock, or for back pain with no clear cause). © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Naeem et al. 2020) 62  Back Pain Natural approach — herbal medicine: Use anti-inflammatory herbs (already covered), focusing on: Devil’s Claw, turmeric, ginger and Boswellia. Where stress is a key trigger / mediator, nervine herbs can relax musculature and hence reduce tension on joints, e.g.: Lemon balm 300–600 mg Passionflower 1 tsp. dried Chamomile 1 tbsp herb infused 2–3 x daily dried herb infused Raises GABA levels Binds to GABA through inhibition of GABA receptors. Anti-inflammatory transaminase Modulates GABA pathways. (COX-2 and NF-kβ inhibition). (Srivastava et al. 2009; Yu et al. 2020; Pourhabibi-Zarandi et al. 2021) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 63  Back Pain Natural approach (cont.): Referral is often advisable, e.g., to an acupuncturist, osteopath etc. Generally, movement is fundamental for back pain recovery. Pilates and yoga are often beneficial. Ensure appropriate supportive footwear (to avoid excessive mechanical load through the spine). Steer people away from pain avoidance behaviour through education. Hydrotherapy (recommendations as for OA). Apply essential oils mixed in a carrier oil (e.g., almond). Lavender and frankincense (relaxing and anti-inflammatory); peppermint (anti-spasmodic). © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 64  Ankylosing Spondylitis Axial Spondyloarthritis in an umbrella term for types of chronic inflammatory arthritis Ankylosing spondylitis = from primarily affecting the spine and sacroiliac the Greek ankylos (crooked) joints (SIJs). It includes ‘non-radiographic and spondylos (joint of the back) axial spondyloarthritis’ (no x-ray findings) and ‘ankylosing spondylitis’ (AS). AS commonly begins between 20 and 30 years of age, and has a male-to-female ratio of ~ 3:1. This is a common AI condition that is certainly under-diagnosed. (MacMillan et al. 2021) 65 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Enthesitis = inflammation Ankylosing Spondylitis where a ligament or tendon attaches to bone Signs / symptoms: Chronic back pain and stiffness (especially in mornings, > 30 minutes). Often improves with movement. Typically starts as SIJ pain. Peripheral enthesitis (e.g., Achilles tendonitis, plantar fasciitis) and arthritis. Extra-articular manifestations: Uveitis (~25%), psoriasis (~10%), IBD (~6.5%). Systemic symptoms (e.g., fever, fatigue). In advanced stages, a loss of lumbar lordosis and an exaggerated thoracic kyphosis. (MacMillan et al. 2021) 66 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Il-23R =interleukin Ankylosing Spondylitis 23 receptor Causes / risk factors — genetics: Note: Dysfunction of the HLA-B27 — over 90% of AS patients have IL-23 / Th17 signalling the gene. Although the full mechanism is axis has been identified not clear, it is thought that molecular as a key driver of chronic mimicry between microbial antigens and inflammation in AS. HLA-B27 is one of the driving factors in AS. Il-23R SNPs — several SNPs in the IL-23R gene have been associated with AS. ERAP1/2 — likely associated with mistaken antigen presentation in conjunction with molecules such as HLA-B27. (Zhu et al. 2019) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 67  Ankylosing Spondylitis Causes / risk factors (cont.): Biomechanical stress — associated with microdamage from repetitive strain, which can promote chronic inflammation in genetically susceptible individuals. Microbial cross-reactivity (with HLA-B27) — Klebsiella pneumoniae has a strong connection to AS. Other microbial links include P. gingivalis, salmonella, shigella, chlamydia and campylobacter. GI inflammation — strongly associated with AS. Gut mucosal inflammation is thought to be present in approx. 70% of AS patients. This is reinforced by the prevalence (~6.5%) of IBD in AS. (Garcia-Montoya et al. 2018; Gracey et al. 2020; Mauro et al. 2021; Beterams et al. 2022) 68 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Ankylosing Spondylitis Causes / risk factors (cont.): Gut dysbiosis patterns — more prevalent in AS. E.g., ↓ F. prausnitzii, ↑ E. coli. Impaired intestinal barrier — upregulated zonulin, high serum LPS levels and a thin mucosal barrier have been linked with AS. This = ↑ proinflammatory cytokines (e.g., Il-17). (Mauro et al. 2021; Sagard et al. 2022) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 69  Ankylosing Spondylitis Natural approach: CNM Naturopathic Diet; dairy exclusion appears to show benefit. Studies have highlighted potential benefits from a ‘low starch diet’ in AS. This has been associated with lower ESR levels. The symptomatic benefits are thought to relate to reduced growth of intestinal microbes (e.g., klebsiella) and reduced LPS absorption. Fasting appears to reduce pain and stiffness in AS, likely through its GIT-supporting actions, and the positive effects on immune-modulation (e.g., ↓ circulating monocytes and inflammatory cytokines). (Almeneessier et al. 2019; Adiguzel et al. 2022; © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. Buono et al. 2022; Popa et al. 2022) 70  Ankylosing Spondylitis Natural approach (cont.): Restore gut health — consider a 5R protocol (see GI lecture). Lactobacillus based probiotics (e.g., casei, rhamnosus GG) appear to provide benefits in AS. Nutrients: Functions: Vitamin D High serum levels of vitamin D = reduced risk of AS. Optimise levels Increases T-reg activity and suppresses Th17 and Th1. Resveratrol Reduces Th17 cells; downregulates NF-KB 200 mg / day and COX-2. Also helpful for gut inflammation. Omega-3 High dose fish oils have been shown 1 g+ of EPA to reduce AS disease activity in 21 days. (Baharav et al. 2007; Singh et al. 2017; Xu et al. 2018) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 71  Ankylosing Spondylitis Natural approach (cont.): Use anti-inflammatory herbs (already covered), focusing on: Devil’s Claw, turmeric, ginger and boswellia. Consider turmeric-ginger shots. Manual therapy (e.g., osteopathy) — to maintain mobility. Exercise — especially key for maintaining spinal / rib mobility. Incorporate daily stretching (e.g., Pilates). Ensure extension based spinal stretches. Consider posture (e.g., desk setup?). Breathing exercises — to maintain thoracic mobility. E.g., in for 3 secs, hold 4 secs, out for 5 secs; Wim Hoff. Contrast showers; Epsom salt baths (500 g‒1 kg). © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 72  Osteoporosis Osteoporosis = low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Signs / symptoms: Asymptomatic until a fracture occurs. Most common fracture locations: vertebrae, hip (femur), distal radius. Vertebral ‘crush’ fractures — results in loss of height and kyphosis. Hip fractures in particular correlate with an increase in mortality. The mortality after 1 year of a hip fracture is between 20 and 40%. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 73  PTH = parathyroid Osteoporosis hormone Bone remodelling: Bone is an active tissue that undergoes remodelling throughout life. Osteoclasts (OC) ↑ the production of enzymes that dissolve minerals and protein in bone. Osteoblasts (OB) create a protein matrix primarily of collagen, resulting in remineralisation of the bone. Various substances affect this balance, e.g., PTH, oestrogen, vitamin D, corticosteroids, acidosis etc. Osteoporosis results from OC bone resorption not being compensated by OB bone formation. Osteoclast 74 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  Osteoporosis Causes / risk factors: Increasing age — peak bone mass is attained by age 25; age-related bone loss of 0.5-1% per year begins at age 40. Female / post-menopause — accelerated bone loss from the oestrogen deficient state. Oestrogen normally inhibits OC formation and induces OC apoptosis. Low body weight — a direct route of increased mechanical stress and load from the weight itself; and an indirect route of peripheral aromatisation of androgens to oestrogens. (Knoke et al. 2003; Mohamed et al. 2003; Prentice, 2004; Faienza et al. 2013) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 75  See nutrition year 1, Osteoporosis minerals lecture Causes / risk factors (cont.): Dairy products — epidemiology research reveals that countries with high dairy intakes have higher rates of osteoporosis and hip fractures. High red meat — acid-forming (linked to high methionine content). Nutrient deficiencies — e.g., vitamin D (facilitates intestinal calcium absorption); calcium (needed to mineralise bone architecture); magnesium (vitamin D co-factor). Carbonated beverages — high acid load due to phosphoric acid. Caffeine and alcohol — decreases intestinal calcium absorption. (Cheraghi et al. 2019; Campion et al. 2020; Chen et al. 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 76  BMD = bone Osteoporosis mineral density Causes / risk factors (cont.): Smoking — upregulates MMPs which break down collagen. Nicotine binds to OBs and promotes cell death. Inactivity — mechanical forces stimulate OBs. Hypochlorhydria — calcium must be ionised by HCl to be absorbed in the intestines. Consider causes, e.g., PPI use, chronic stress. Inflammation — chronic inflammation has been clearly linked to osteoporosis. hsCRP levels are associated with BMD. Inflammatory cytokines such as Il-1 and Il-6 promote osteoclast activity. Drugs — e.g., corticosteroids promote OC activity. (Ganesan et al. 2005; Carter et al. 2014; Al- Bashaireh et al. 2018; Ginaldi et al. 2019 ) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 77  Osteoporosis Causes / risk factors (cont.): Gut dysbiosis: – Intestinal bacteria play a key role in producing vitamin K2. – Low SCFA production is linked to osteoporosis. SCFAs regulate the differentiation of osteoclasts and inhibit bone resorption. – Some microbes (e.g., Lactobacillus, Bifidobacterium) promote mineral absorption (e.g., calcium, magnesium). – A diverse gut microbiome can promote the production of T-reg cells in the intestine. Other diseases – e.g., Cushing's, coeliac (malabsorption), hyperparathyroidism etc. (Ding et al. 2020) © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 78  Osteoporosis Investigations: Dual energy x-ray absorptiometry (DEXA) measures BMD. Often taken in the hip and lumbar spine. Alternative: Urinary bone resorption. Common conventional treatment: Bisphosphonates — inhibit osteoclast activity. Side effects: Oesophagitis, gastritis, jaw osteonecrosis. Calcium carbonate — poorly absorbed. HRT — for post-menopausal women. Synthetic drugs linked to breast cancer, endometrial cancer and thrombosis. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 79  Osteoporosis Natural approach — dietary: Based around the CNM Naturopathic Diet, with a focus to: Avoid / limit: Dairy products, carbonated beverages, coffee, alcohol, limit red meat intake. Eat / include: ‒ Anti-inflammatory foods — e.g., high omega-3 ‘SMASH’, flax / chia seeds; high phytonutrient foods; turmeric, ginger. ‒ Green leafy vegetables for their abundance of minerals and vitamins for bone health, e.g., calcium, magnesium, boron. ‒ Phytoestrogens if post-menopausal (e.g., organic fermented soy). © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 80  ESCEO = European Society for Osteoporosis Clinical and Economic Aspects of Osteoporosis and Osteoarthritis Natural approach (cont.): Adequate dietary protein is needed to support the bone framework ( collagen). The ESCEO recommends a protein intake of 1.0‒1.2 g / kg of bodyweight / day with at least 20‒25 g of high-quality protein at each main meal. ‒ However, a high-protein diet ↑ urinary excretion of calcium. It promotes acidosis, which the body buffers with calcium (taking it from bones). Address other risk factors for osteoporosis as needed, e.g., stop smoking, support gastric HCl / digestion, optimise body weight, support the gut microbiome etc. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 81  See nutrition year 1, Osteoporosis minerals lecture Natural approach (cont.): Nutrients: Functions: Calcium Needed to mineralise bone architecture. Food sources: Calcium must be ionised to dark green leafy be absorbed in the intestines veg (e.g., kale), (dependent on gastric HCl) — support sardines, sesame as needed with bitters, betaine HCl etc. seeds / tahini, Avoid a high intake of phytates which almonds impair absorption (esp. wheat bran which reduces intestinal absorption). If supplementing: Salt increases urinary calcium loss (by 500 mg / day 4‒5 % for each 500 mg of sodium ingested). © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. 82  See nutrition year 1, Osteoporosis vitamins lecture Natural approach (cont.): Nutrients: Functions: Vitamin D Vitamin D facilitates calcium absorption in the Optimise levels intestine and is involved directly in bone turnover. (dose higher if Low levels are associated with bone loss and fractures. VDR SNP) Vitamin D can also improve muscle function and balance, leading to reduced risk of falling. Vitamin K2 Required for the production of osteocalcin, 50‒100 mcg, which draws calcium into bone tissue and and support provides the protein matrix for mineralisation. through the Osteocalcin synthesis by osteoblasts is microflora. regulated by active vitamin D (calcitriol). (Purwosunu et al. 2006; Kuchuk et al. 2009) 83 © CNM: Nutrition Year 2: Musculoskeletal Health. BQ.  See nutrition year 1, Osteoporosis vitamins lecture Natural approach (cont.): Nutrients: Functions: Magnesium A co-factor for alkaline phosphatase, 200‒400 mg which plays a role in bone mineralisation A co-factor for the enzyme responsible for the conversion of 25-(OH)D3 to 1,25-(OH)2D3. Other Boron — reduces urinary excretion of calcium minerals: and magnesium and increases oestradiol Consider a and testosterone in postmenopausal women. multi-mineral Zinc — inhibits osteoclast activity; synthesis of supplement metalloenzymes for production of bone matrix. Manganese — assists bone calcium deposition. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Aydin et al. 2010) 84  Osteoporosis Natural approach (cont.): Herbs / nutrients: Functions: Nutritive herbs: Horsetail (Equisetum arvense) is a nutritive herb, especially rich in silica, which is good for bone mineralisation. Nettle (Urtica dioica) is also nutritive. Combine 1 tsp each per tea as a hot infusion. 2‒3 x daily. Tissue salts: Calc. fluor — improves mineralisation (osteoid formation). 1 each x 3 daily Calc. phos — helps support osteoid formation as well as improving calcium absorption, metabolism and utilisation. Silica — works with calc. phos to support mineralisation. Useful where heavy metals compromise bone structure. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Arbabzadegan et al. 2019) 85  Osteoporosis Natural approach — exercise: Focus on a minimum of 3 x weekly, 30 minutes sessions of mostly weight-bearing exercise to promote osteoblast activity. Good options include walking (e.g., brisk), weight training (free weights), stair climbing, dancing, yoga, Pilates, Tai Chi and hiking. Resistance exercise is also beneficial by acting on tendonous attachments to bone. These exercises also help co-ordination and hence prevent falls. © CNM: Nutrition Year 2: Musculoskeletal Health. BQ. (Hong & Kim, 2018) 86  Summary Quiz! 1. What is the typical daily pattern of inflammatory LBP? 2. 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