Integrative Approaches To Common Conditions

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Hal S Blatman, MD, DAAPM, ABIHM

Presenter/Faculty Disclosure

• Faculty: Dr. Hal S Blatman • Relationships with commercial interests:

– Grants/Research Support: none – Speakers’ Bureau: Standard Process – Consulting Fees: none – Other: none

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Objectives • Review evidence-based use of dietary supplements and complimentary modalities of treatment for a variety of common conditions such as gastro-intestinal disorders that include IBS, reflux, cholelithiasis, and constipation. • Describe evidence-based use of dietary supplements and complimentary modalities of treatment for a variety of common conditions including pain management and substance abuse. • Discuss evidence-based use of dietary supplements and complimentary modalities of treatment for a variety of common conditions such as men’s health including prostate disorders, urolithiasis, and erectile dysfunction. • Review evidence-based use of dietary supplements and complimentary modalities of treatment for a variety of common conditions including rheumatologic and neurologic disorders.

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Gastro-Intestinal Health

•  Irritable bowel syndrome • Gastro-esophageal reflux disease • Peptic ulcer disease • Cholelithiasis • Recurring abdominal pain in pediatrics • Constipation

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Overview

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• Psychosocial factors • Stress • Enteric infection • Food sensitivities/allergies

– gluten, fructose, lactose, sorbitol, etc. • Diet • Visceral hypersensitivity • Orient thought to prescribe what helps the body

heal, not to block biological process

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Definitions and Basics!

Prebiotic non-digestible food ingredient that promotes the growth of beneficial

microorganisms in the intestines

• Partially hydrolyzed guar gum1

– Water soluble, non-gelling fiber – Reduced sx in constipation-predominant and diarrhea-predominant forms of IBS – Decreased abdominal pain – Improved quality of life during and after treatment – Prebiotic properties

• Increases colonic short-chain fatty acids • Increases Lactobacilli, Bifidobacteria

• Prebiotic review (stimulate bacterial growth and gas production)2

– Fructo-oligosaccharides (FOS) and inulin • Linked fructose molecules • Bifidogenic

– Galactooligosaccharides (GOS) • Linked galactose units • Selectively fermented in colon • Bifidogenic, Lactobacilli also

7 1.  Nutrition, 2006. Mar;22(3):334-42.!2.  Alt Med Rev., 2009. 14(1)!

Side Effects/Dose

• Shorter chain — more abdominal side effects – Flatulence 1-2 g/day if sensitive

• 2.5-10 g/day therapeutic • Diarrhea — osmotic due to fibers not

broken down 10-50+ g/day

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Fiber-Soluble vs Insoluble

• Soluble fiber led to significant IBS improvement – Psyllium – Ispaghula—dried seeds of So. Asian plantain – Calcium polycarbophil—drug used as stool stabilizer

• Rx constipation, diarrhea, abdominal discomfort (bulking)

•  Insoluble fiber no benefit, maybe worse – Corn, wheat, bran

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Bijerk C., et al.,: Systemic review: the role of different types of fiber in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 19:245-251, 2004.!

Constipation

• Stool softener / bulking herbs – Psyllium with water during the meal

• Psyllium will hold the water and keep stool soft • Suggest 2 caps with meals

– Inulin studies show stool softer, BMs more regular – Slippery Elm (Ulmus)

• Laxative – Cascara sagrada – Senna (Cassia senna) – Aloe (aloe spicata and aloe vera)

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Constipation-Minerals

• Magnesium Oxide — 1-2 tabs 2-4x/day – Safely provides ‘push’ – Perhaps threshold – Inexpensive – 10% absorbed for other effects of Mg – 20-30 g/day=>hypokalemia and metabolic alkalosis1

– Elevates serum magnesium levels, not dangerous2

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1.  Urakabe S., et al., Hypokalemia and metabolic alkalosis resulting from overuse of magnesium oxide. Jpn. Circ. J. October 1, 1975;39(10);1135-7.!

2.  Tatsuki M., et al., Serum magnesium concentration in children with functional constipation treated with magnesium oxide. World J. Gastroenterol. February 14, 2011;17(6);779-83.!

Constipation Combination Formulas

• Padma Lax Tibetan herbal formula1

– Aloe, calumba root, cascara bark, frangula bark, rhubarb root

– STW5 decreases dyspepsia of stress (rat separation stress)

50% (v/v) hydroethanolic fresh plant extract of Iberis amara L. (Brassicaceae, 15%) whole plants and the 30% hydroethanolic extracts of Melissa officinalis L. (Lamiaceae, 10%) leaves, Matricaria chamomilla (Compositae, 20%) flowers, Carum carvi L. (Apiaceae, 10%) fruits, Mentha piperita L. (Lamiaceae, 5%), Angelica archangelica L. (Apiaceae, 10%) roots, Silybum marianum (L.) Gaertn. (Compositae, 10%) fruits, Chelidonium majus L. (Papaveraceae, 10%) and Glycyrrhiza glabra L. (Leguminosae, 10%).

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1.  Sallon S., et al., A novel treatment for constipation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula. Digestion. 2002;65(3):161-171.!

2.  Abdel-Aziz H1, et al., Novel sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW5. Phytomedicine. 2015 May 15;22(5):588-95.!

Irritable Bowel Syndrome

• Artichoke1 (Cynara scolymus) leaf extract 320 mg/cap 6/day in 10 days decreased 3 of: abdominal pain/bloating/flatulence/right-sided abdominal cramps/constipation

• Turmeric standardized extract 72 mg or 144 mg/day decreased symptoms2

•  L-glutamine — primary fuel for enterocytes – 500 mg caps, open 4, qid, or powder…4-5 g, qid; careful for diabetics

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1.  Walker AF., et al., Artichoke leaf extract reduces symptoms of irritable bowel syndrome in a post-marketing surveillance study. Phytother res. 2001;15:58-61.!

2.  Bundy R., et al., Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: pilot study. J Alten Complement Med. 2004;10(6):1015-1018.!

Inflammatory Bowel Disease

• Lindsay trialed patients with ileocolonic or colonic Crohn’s disease 15 g oligofructose-enriched inulin/day x 21 – Crohn’s disease activity decreased – No increased flatulence – Increase anti-inflammatory IL-10 CD11c+dendritic

cells – Increase toll-like receptor 2,4 (TLR2 and TLR4)

expression – Suggest immunomodulatory activity

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Inflammatory Bowel Disease

• Adrographis vs mesalazine randomized, double blind trial for mild to moderately active ulcerative colitis — similar improvement vs placebo1

• Boswellia several studies, 1-decreased CrP2

• Rehmannia — improvement rheumatoid arthritis uncontrolled trials3

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1.  Tang T., et. al., Aliment Pharmacy there. 2011;33(2):194-202.!2.  Eleventh European Congress of Rheumatology. 1987;5(supplement issue):175.!3.  Hu C., Chin Med J. 1065;51:290.!

Other Botanicals • Peppermint oil1 (menthol and methyl salicylate)

– Antispasmodic – Analgesic (kappa receptor agonist) – 200-400 mg enteric (*aromatic or pungent spices are likely to add additional effects) caps t.i.d.

between meals – 100-200 mg children – May cause heartburn, decrease lower esophageal sphincter tone

• Fennel, caraway seeds – Antispasmodic, prevent bloating and gas – 1 tsp with food, tea, oil, alcohol extract

• Aloe vera and Matricaria recutita mixture2

– Decreased colonic TNF-α/lipid peroxidation/reduced transit time in stressed rats • Cramp bark (Viburnum opulus) — antispasmodic, mostly smooth muscle • Valerian (Valeriana), Slullcap (Scutellaria latieriflora) — sedative and nervine tonic

herbs • Chamomile (Matricaria recutita) — mild sedative, antispasmodic, non-demulcent, anti-

inflammatory – 1-3 g flowers, seeped, 3-4x/day

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1.  Pittler M., et al., Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis, Am J Gastroenterol. 83:1131-1135, 1998.!

2.  Asadi-Shahmirzadi A1., et al., Benefit of Aloe vera and Matricaria rectita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects, Chin J Integr Med 2012 Dec 21.!

Inflammatory Bowel Disease • Studies support supplementation with

– Folates – B12, B6

– E and C – Vitamin D, K – Zinc – Selenium – Magnesium – Chromium — can reduce steroid-induced diabetes in humans – Fish oils – Glutamine – N-Acetylglucosamine (NAG) — protect bowel mucosa from toxic damage1

– N-Acetylcysteine — needed for synthesis of glutathione; 800 mg/day + mesalamine2

– Phosphatidylcholine down regulates TNFα signaling 500 mg qid 80% got off steroids3

– Probiotics – Prebiotics

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1.  Salvatore S., et. al., A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in pediatric chronic inflammatory bowel disease. Aliment Pharmacy There. 2000 14:1567-1579.!

2.  Guijarro O., et. al., N-Acetyl-l-cysteine combined with melamine in the treatment of ulcerative colitis: randomized, placebo-controlled pilot study. World J Gastroenterol. 2008 14:2851-2857.!

3.  Stremmel W., et. al., Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 147:603-610.!

Gastroesophageal Refulx Disease

• Demulcent Botanicals (mucilaginous) – mucoprotection, soothes – Licorice (Glycyrrhiza glabra) deglycyrrhizinated is effective also, safe for long term

use – 2-4 x 380 mg tablets before meals1

• Slippery Elm (Ulmus fulva) Root Bark Powder – Relieve symptoms, promote healing of irritated esophageal/gastric mucosa

• Marshmallow (Althea officials)1

– GERD, pharyngitis, wound healing, cough, bronchitis – 5-6 g/day, infusion or root

• L-glutamine 2-5 g qid plus symptomatic indigestion • Acid — maybe acid deficient, and need hydrochloric acid with meals

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1. Johnson LP., Pocket Guide to Herbal Medicines, 2002 Blackwell Science Malden MA!

Peptic Ulcer Disease • Vitamin C — several studies, H. pylori eradication 2 weeks 1000

mg/day1

• Polyunsaturated fatty acids — several studies, anti-H. pylori effects, EPA, GLA (black currant seed oil) 1 g each daily x 4 weeks2,3

• Zinc — healing 3x faster than placebo 40 mg/day x 4 weeks4

• L-glutamine — prevent stress ulcers in burn patients; ASA induced gastric lesions, peptic ulcers (2-4 g q.i.d.+sx) caution with diabetics5

– Inhibits gastric lesions produced by oral aspirin6

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1.  Kockar C., et al., Helicobacter pylori eradication with beta carotene, ascorbic acid, and allicin. Acta Medica (Hradec Kralove).. 2001. 44:97-100.!

2.  Thompson L., et al., Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter pylori: a possible explanation of the effect of diet on peptic ulceration. Gut 1994. 35:1557-1561.!

3.  Frieri G., Polyunsaturated fatty acid dietary supplementation: an adjuvant approach to treatment of Helocobacter pylori infection. Nut Res 2000. 20:907-916.!

4.  Frommer D., The healing of gastric ulcers by zinc sulfate. Med J Aust, 1975. 2:793-796.!5.  Yan R., early enter feeding and supplement of glutamine prevent occurrence of stress ulcer following severe thermal injury.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi. 1995. 11:189-192.!6.  Mitra R., Inhibition of mast cell population by L-glutamine in aspirin-induced ulceration in rat stomach. J Physiol Pharmacol.

October 1, 1977;21(4):374-8.!

Peptic Ulcer Disease Botanicals

• Turmeric (Curcuma longa) – Dyspepsia and epigastric pain, ulcer – Root powder caps 600 mg 5x/day 12 weeks1

– H2 histamine receptor blocker2 – Inhibits 11B-HSD13

• Cabbage (Brassica oleracea) juice – Studies from 1050’s, rich source glutamine, sulforahanes

• Licorice • Capsacin — suspected to exacerbate, but 2.5 mg caps daily x5 weeks leads to clinical

improvement4

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1.  Prucksunand C., et al., Phase II clinical trial on effect of the long turmeric (Curcuma long Linn) on healing peptic ulcer. Southeast Asian J Trop Med Public Health. 2001. 32:208-215.!

2.  Kim D., et al., Curcuma longa extract protects against gastric ulcers by blocking H2 histamine receptors. Bill Pharm Bull. 2005. 28:2220-2224.!

3.  Hu GX et al., Curcumin as a potent and selective inhibitor of 11B-hydroxysteroid dehydrogenase: improving lipid profiles in high-fat-diet-treated rats. PLoS One. 2013;8(3):e49976. Pub 2013 MR 22.!

4.  Bortolotti M., et al., The treatment of functional dyspepsia with red pepper. Alien Pharmacy There. 2002. 16:1075-1082.!

Cholelithiasis • Monounsaturated and polyunsaturated fats inhibit

cholesterol cholelithiasis1

• Fish oil decrease biliary cholesterol saturation and enhance bile flow2

• Proinflammatory fats (arachidonic acid) increase cholesterol saturation and disrupt gallbladder epithelium3

• Lecithin — increase in biliary phospholipids, may aid in prevention 500-1000 mg/day4

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1.  Cohen B., et al., Dietary fat and fatty acids modulate cholesterol cholelithiasis in the hamster. Lipids. 1992. 27:526-532.!2.  Berr F., et al., Dietary n-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.

Hematology 1992. 16:960-967.!3.  Rakel D., Cholelithiasis. Integrative Medicine 2nd ed. 2007 Saunders Philadelphia 491-497.!4.  Tuzhilin S., et al., The treatment of patients with gallstones by lecithin. Am J Gastroenterol. 1976 65:231.!

Cholelithiasis

• Vitamin C decreases cholesterol crystal formation1

• Magnesium decreases gall stones2

• Vitamin E may help3

• Calcium (gluconate)4

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1.  Gustafsson U., et al., The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of nucleation time. Eur J Clin Invest. 1997 27:387-391.!

2.  Tsai C., et al., Long-term effect of magnesium consumption on the risk of symptomatic gallstone disease among men. Am J Gastroenterol. 2008 103:375-382.!

3.  Christensen F., et al., Alimentary production of gallstones in hamsters II. Acta Physiol Scand. 1953 27:315-320.!4.  Moerman C., et al., Dietary risk factors for clinically diagnosed gallstones in middle-aged men: a 25-year follow-up study

(the Zutphen Study). Ann Epidemiol. 1994 4:248-254.!

Cholelithiasis — Herbs • Chelidonium (Chelidonium majus L)

– Choleretic (increases bile production) – Aerial parts assist liver and gallbladder function, spasmolytic to GI tract,

stimulates bile flow, anti-inflammatory – 2-4 g/day – Short term use; contraindicated if liver damage

• Peppermint (Mentha x piperita L) – Cholagogue (promotes bile discharge) – Stones reduced in size and number, 6+ months

• St Mary’s Thistle (Silybum marianum (L) Gaertn.) {milk thistle} Leaf – Silymarin, flavonolignan complex is main active fraction – Choleretic, galactagogue (promotes flow of mothers’ milk)

– Hepatoprotective, increases intracellular glutathione – 4-9 g/day of seed – No restrictions for long term use

23 Bone and Mills, Principles and Practice of Phytotherapy 2nd Ed., Churchill Livingstone 2013.!

Cholelithiasis Gall Bladder Flush

• Controversy in efficacy and risk of getting stones stuck but works very well (personal exp.)

• Soften stones in advance (apple pectin supplement)

• Thin bile (Choleretic, Cholagogue)

• Drink at night glass with 1/2 olive oil; 1/2 lemon juice

• Lie on right side • BM with stones in the morning

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Recurring Abdominal Pain in Pediatrics

• Stop using formula, instead of mother’s milk prescribe goat’s milk (add folate) • Psyllium 1 tsp (2g) in 8 oz up to t.i.d. • Chamomile (Matricaria recutita)

– Tea reduces colic episodes1

• Peppermint (Mentha piperita) – Tea or capsules

• Ginger (Zingiber officinale) – Improve gastric motility, antispasmodic

• Slippery Elm (Ulmus fulva) – Protects GI tract from irritation – Helpful for children with dyspepsia – Tea from powdered bark

• Lemon Balm (Melissa officinalis) – Relax bladder, stomach, uterus

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1.  Weizman Z., et al., Efficacy of herbal tea preparation in infantile colic. J Pediatr. 1993 122:650-652.!2.  Murray M., Healing Power of Herbs. 1995 Prima Publishing Rocklin, CA.!3.  Bone and Mills, Principles and Practice of Phytotherapy 2nd Ed., Churchill Livingstone 2013.!

Men’s Health

• Benign prostatic hyperplasia • Urolithiasis • Chronic prostatitis • Erectile dysfunction

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Benign Prostatic Hyperplasia • Beta-sitosterol (found in most plants)

– Phytosterol similar to cholesterol – High levels in saw palmetto, pygeum, stinging nettle – Benefit in treating BPH1

– 60 mg bid • Zinc (30 mg/day)

– Reduces BPH2

– Many studies absorption decreased by coffee, thiazide diuretics, steroids – Decreases production of DHT, and DHT binding

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1.  Klippel K., et al., A multicentric, placebo-controlled, double-blind clinical trial of B-sitosterol for the treatment of benign prostatic hyperplasia. Br J Urol. 1997 80:427-432.!

2.  Fahim M., et al., Zinc treatment for the reduction of hyperplasia of the prostate. Fed Proc. 1976 35:361.!

Benign Prostatic Hyperplasia

• Saw Palmetto (Serenoa repens) – Sterol beta-sitosterol – Improves nocturia, residual urine volume,

urinary flow with BPH – Does not affect PSA1

– 160 mg bid at least 8 weeks

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1.  Gerber G., et al., Saw palmetto in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urology. 1998 51:1003-1007.!

Benign Prostatic Hyperplasia

• Rye Grass Pollen (Secake cereake)

– Use in Europe since 1970’s, response rate 70%1

• Inhibits prostatic cell growth2

• Inhibits inflammatory prostaglandins and leukotrienes3

• 126 mg tid of 20:1 standardized extract

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1.  Buck A., et al., Treatment of outflow tract obstruction due to benign prostatic hyperplasia with the pollen extract, Cernilton: a double-blind, placebo-controlled study. Br J Urol. 1990 66:398-404.!

2.  Habib F., et al., Identification of a prostate inhibitory substance in a pollen extract. Prostate. 1995 26:133-139.!

3.  Loschen G,. et al., Inhibition of arachidonic acid cascade by extract of rye pollen, Arzneimittelforschung. 1991 41:162-167.!

Benign Prostatic Hyperplasia

• Pygeum africanum (Prunus africana) – Bark African plum tree sterols – Reduce inflammation – Increase prostatic and seminal fluid secretions – Decrease nocturia and other parameters1

– 100-200 mg/day

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1.  Ishani A., et al., Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: s systematic review and quantitative meta-analysis. Am J Med. 2000 109:654-664.!

Urolithiasis • Calcium — studies in 1990’s calcium inversely related to

stone formation • No consensus regarding dietary oxalate and stone formation

(nuts, vegetables, chocolate) • Vitamin C — no evidence for increased stones (can be metabolized

to oxalate)

• Suggest decrease animal protein (high purine increases uric acid secretion)

• Fish oil may reduce urinary oxalate • Uric acid stones — should reduce purines1

– Organ meats, legumes, mushrooms, spinach, alcohol, sardines, poultry

31 1. Cameron M., et al., Uric acid nephrolithiasis. Urol ClinNorth Am. 2007 34:335-346.!

Urolithiasis • Factors in urine that inhibit crystallization

– Magnesium — complexes oxalate – Citrate — complexes calcium – Pyrophosphate — impairs crystallization of calcium oxalate1

• Oxalobacter formigenes degrades dietary oxalate2

– O. formigenes (anaerobe in colon) is killed by Quinolone

• Crataeva nurvala – Studies show reduced oxalate stone formation3

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1.  Whitfield H, Mallick N., Ranal calculi. Medicine 1995:199-204.!2.  Siva S., et al., A critical analysis of the role of gut Oxalobacter foreignness in oxalate stone disease. BJU Int. 2009;103(1):

18-21!3.  Anand R., et al., Antiurolithiatic activity of Crataeva nirvana ethanolic extract on rats. Fitoterapia. 1993;64(4):345—350.!

Chronic Prostatitis

• Zinc supplementation does not raise prostate zinc concentration, but reverses prostatitis-induced infertility – More than 40 mg/day can depress serum

copper and impair immunity – Take separate from quinolone antibiotics (2,6

hrs) (Rakel)

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Chronic Prostatitis

• Saw Palmetto – Inhibits enzymes that convert arachidonic acid to PgE2

• Rye Grass Pollen – Blocks inflammatory prostaglandins/leukotrienes

• South African Star Grass (Hypoxis rooperi) – B-sitosterol reduces inflammation, cholesterol

• Clivers (Galium aparine) – Anti-oxidant flavinoids, diuretic, reduces inflammation – 30-40 drops tid in glass water

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Chronic Prostatitis

• Agrimony (Agrimonia eupatoria) – Flower rich in catechins, reduce inflammation – 3 g or herb, 30 drops extract in water tid

• Stinging Nettle (Urtica dioica) – Polysaccharides inhibit prostaglandin and

leukotriene molecules – 120 mg bid

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Painful Urination • Marshmallow Root (Althaena officials)

– Soothes inflamed mucous membranes • Eryngo (Eryngium campestre)

– Herbal tincture from leaves, roots, flowers — assuages dysuria • Cranberry (Vaccinium macrocarpon)

– Proanthocyanidins prevent bacteria adherence to urothelial mucosa

• Uva ursi (Arctostaphylos uva-ursi)

– Contains arbutin, potent antiseptic – Hydrolyzed to hydroquinone, best in alkaline urine

• There are also homeopathic remedies 36

Erectile Dysfunction

• Korean red ginseng 2-3 g/day significant improvement;1 (meta-analysis of 6 randomized controlled studies)

• Treat stress and anxiety – Valerian, Nervine tonics: damiana, skullcap

• Adaptogenic herbs: Withania, Rhodiola, Korean ginseng •  Improve male hormone levels: saw palmetto, Tribulus, Withania •  Improve circulation: ginger, Ginkgo, prickly ash • Consider injection of platelet-rich plasma to penis, G-spot

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1.  Jang D., et al., Red ginseng for treating erectile dysfunction: a systematic review. Br J ClinPharmacol. 2008;66(4):444-450.!

2.  Bone and Mills, Principles and Practice of Phytotherapy 2nd Ed., Churchill Livingstone 2013.!

Neurological Disorders

• Alzheimer’s disease • Headache • Peripheral neuropathy • Multiple sclerosis • Parkinson’s disease

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Alzheimer’s Disease • Nutrients can be added to medication regimens • B vitamins

– B3 memory improvement1

– Folate reduces risk, decrease homocysteine2

• Vitamin E – 2000 u/day slows progression of midstage AD3 (protects cell membranes from

oxidative damage)

• Phosphatidylserine (100-300 mg/day) – Improves short-term memory, mood, concentration, ADL’s4

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1.  Zhang X., et al., Protective effects of nicotinic acid on disturbance of memory induced by cerebral ischemia-reperfusion in rats. Clin J Pharm Toxicol. 1996 10:178-80.!

2.  Corrada M., et al., Reduced risk of Alzheimer’s disease with high folate intake: the Baltimore Longitudinal Study of Aging. Alzheimers Dement. 2005 1:11-18.!

3.  Sano M., A controlled trial of selegiline, alphatocopherol, or both as treatment for Alzheimer’s disease: the Alzheimer’s Disease Cooperative Study. N Engl J Med. 1997 336:1216-1222.!

4.  Crook T., et al., Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull. 1992 28:61-66.!

Alzheimer’s Disease • Coenzyme Q10 (100-400 mg/day) several studies

– Neuroprotective, antioxidant • Ginkgo biloba (up to 240 mg/day)

– Improves short term memory and concentration • Vitamin E + Ginkgo + Coumadin

–  monitor coagulation parameters, do not deny care

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1.  Le Bars P., et al., A placebo-controlled, double blind, randomized trial of an extract of Ginkgo biloba for dement. JAMA. 1997 278:1327-1332.!

Alzheimer’s Disease • Huperzine A (50 mg bid)

– Natural anti cholinesterase inhibitor from Chinese club moss – Reverses memory deficits

• Vinpocetine (2.5-5 mg bid) – Periwinkle plant – Increase cerebral blood flow, enhance neuronal metabolism – Beneficial effects on cognitive function2

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1.  Le Bars P., et al., A placebo-controlled, double blind, randomized trial of an extract of Ginkgo biloba for dement. JAMA. 1997 278:1327-1332!

2.  Szatmari S., et al., Vinpocetine for cognitive impairment and dementia. Cochrane Database Syst Rev. 1 2003 CD003119.!

Headache • Magnesium

– Orally, transdermally, intravenously • Riboflavin (B2) 200 mg b.i.d.//5-phosphate form 36 mg

– Important in mitochondrial function • Coenzyme Q10 (100 mg t.i.d. reduced attacks 47.6% at 3 months)1

• Fish oil from many benefits • Alpha-lipoic acid — daily use for 3 months decrease

migraine2

– Mitochondrial cofactor, potent antioxidant

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1.  Rozen T., et al., Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia. 2002 22:137-141.!2.  Magis D., et al., A randomized double-blind, placebo controlled trial of thioctic acid in migraine prophylaxis.

Headache. 2007 47:52-57.!

Headache

• Feverfew (Tanacetum parthenium Leaf) 150 mg tab contain >0.6 mg parthenolide 2-3x/day – Antisecretory (inhibition of platelet aggregation, granule secretion

from polymorphonuclear leucocytes – Anti-inflammatory (inhibits NF-kappaB activation and prostaglandin

biosynthesis) – Migraine prophylaxis effect not immediate

• Butterbur (Petasites hybridus Root) – Dble blind, placebo-cont trial 50 mg b.i.d. decreases attacks 46%

after 4 weeks3

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1.  Rozen T., et al., Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia. 2002 22:137-141.!2.  Magis D., et al., A randomized double-blind, placebo controlled trial of thioctic acid in migraine prophylaxis.

Headache. 2007 47:52-57.!3.  Mauskip A., et al., Headache 2000; May:420.!

Peripheral Neuropathy

• Acetyl-L-carnitine — transport fatty acids into mitochondria – Studies for chemotherapy, diabetes (type 2>1) – Pain, sensory improvement, nerve regeneration,

vibratory perception – Up to 1000 mg po tid

• Alpha-lipoic acid (thiotic acid) – Diabetic neuropathy – Neurogenerative and neuroprotective – 600-1800 mg/day 44

Peripheral Neuropathy • B vitamins

– Benfotiamine (B1, S-benzoylthiamine-O-monophosphate; lipid soluble derivative)

– Penetrates nerves more readily – Increase nerve conduction velocity – 150-300 mg bid for diabetic PN

• Methylcobalamin: B12

– 1500 ucg/day x 2 months improved vibratory perception and HRV (autonomic neuropathy) in diabetics1

• B complex vitamins in balanced dose are likely not dangerous – Up to 4 x B-100 / day for 6 months not harmful (personal prescriptive experience)

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1. Yoshioka K., et al., Effect of methylcobalamin on diabetic autonomic neuropathy as assessed by power spectral analysis of heart rate variations. Horn Metab Res. 1995 27:43-44.!

Peripheral Neuropathy

• Fish oil – Diabetic neuropathy, 1800 mg EPA daily x 48 weeks,

decreased cold/numb sensations,improved vibratory threshold1

– Triglyceride form superior by 70% vs ethyl ester2

• Evening Primrose Oil (GLA>linoleic acid essential component of myelin and neuronal cell membrane) – 360 mg/day 6 months improve neuropathy scores, nerve conduction

velocities, diabetes

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1.  Okuda Y., Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus. J Diabetes Complications. 1996 10:280-287.!

2.  Dyerberg J., Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010 83:137-141.!

Peripheral Neuropathy

• Curcumin (active ingredient in turmeric) – Attenuates diabetic neuropathic pain1 – Heaping tsp (4 g powder) with water or milk bid2 – Safe for long term use2

• Geranium oil – Pain reduction PHN, in 30 min up to 8 hrs3

47

1.  Sharma S., Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF-α. Phytother Res. 2007 21:278-283!

2.  Bone and Mills, Principles and Practice of Phytotherapy 2nd Ed., Churchill Livingstone 2013!3.  Greenway F., et al., Temporary relief of postherpetic neuralgia pain with topical geranium oil. Am J Med.

2003 15:586-587.!

Multiple Sclerosis

• Vitamin D (decrease incidence, alleviate symptoms)

• Alpha-lipoic acid • Glutathione (IV is superior) • N-Acetylcysteine (raises glutathione levels) • Magnesium • B-Complex • B12

48

Multiple Sclerosis • Ashwagandha (Withania somnifera)

– anti-inflammatory, antioxidant, anxiolytic, antidepressant activities1

– 1-6 g powder whole herb 2-3x/day • Ginkgo biloba

– Antioxidant, enhances neurotransmission2

• Marijuana (Cannabis sativa) – MS related symptoms, spasm and tremor3

49

1.  Mishra L., et al., Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Alter Med Rev. 2000 5:334-346.!

2.  Yoshikawa T., Gingko biloba leaf extract: review of biological actions and clinical applications. Antioxid Redox Signal. 1999 9:59!

3.  Zajiek J., et al., Cannabiinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomized placebo-controlled trial. Lancet. 2003 362:1517-1526.!

Parkinson’s Disease • Coenzyme Q10 several studies up to 2400 mg/day. Suggest 400

mg/day. – Other mitochondrial treatments helpful including ozone/oxygen gas in the

blood • N-Acetylcysteine (600 mg bid)

– Unlike glutathione crosses blood brain barrier1

– Protects against cell death in animal models Parkinson’s2

• Vitamin B6

– Can increase peripheral conversion of levodopa to dopamine, avoid with patients taking carbidopa/levodopa3

50

1.  Dringen R., et al., N-acetylcysteine, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as cysteine donor for the synthesis of glutathione in cultured neurons derived from embryonal rat brain. Neurotic Lett. 1999 259:79-82.!

2.  Clark J., et al., Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synucein overexpressing mice. Plos One 5:e12333 2010!

3.  Klawans H., et al., Failure of vitamin B6 to reverse the L-dopa effect in patients on a dopa decarboxylase inhibitor. J Neurol Neurosurg Psychiatry. 1971 34:682-686.!

Parkinson’s Disease • Creatine (by diet and body synthesis)

– Skeletal muscle and crosses BBB – 5 g bid (suggested by Rakel) – Decreases need for ATP1

• Choline (Cytidine diphosphate, citicoline) – Intermediate in phospholipid synthesis – Decreases dopamine reuptake, activates dopamine

hydroxyls and increased dopamine production2

51

1.  Thomas B., et al., Mitochondrial therapies for Parkinson’s disease. Mov Discord. 2010 25 (suppl 1):S155-S160.!2.  Martinet M., et al., Interaction of CDP-choline with synaptosomal transport of biogenic amines and their

precursors in vitro and in vivo in the rat corpus striatum. Experiential. 1978 34:1197-1199.!

Parkinson’s Disease • Green tea (Epigallocatechin Gallate)

– 3 cups/day may decrease risk by 28%1

• Curcumin – Potent antioxidant attenuate loss of glutathione in cultured

dopaminergic cells, reduce cell loss – 450-3000 mg/day, or cook with it – reduces lipid peroxidation and primes Nrf2/ARE pathway (Bone 2013)

• Cowhage (Mucuna pruriens) – Contains levodopa, CoQ10, and reduced NADH

• As effective as levodopa in reducing symptoms2

52

1.  Mandel S., et al., Multifunctional activities of free ea catches in neuroprotectin: ovulation of cell survival genes, iron-dependent oxidative stress and PK signaling pathway. Neurosigals. 2005 j14:46-60.!

2.  Katzensclager R., et al., Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological stdy. J Neurol Neurosurg Pschiatry. 2004 75:1672-1677.!

Pain Management

• Osteoarthritis • Myofascial pain syndrome • Chronic low back pain • Neck pain • Gout • Carpal Tunnel Syndrome/RSI/Epicondylitis

53

Osteoarthritis • Glucosamine

– Lots of studies and with 20 years of experience (negative studies used product that did not work):

• Sulfate or Hydrochloride, never mind chondroitin • Orally only for knees — 500 mg tid • Transdermally for any joint, TMJ to great toe; use HCL • Injectable for any joint, greater efficacy, less side effects, and less expensive than hyaluronate preparations

• Platelet-rich plasma, many studies (recent study shows joint cartilage thickening by MRI)

• Bromelian • Equivalent to diclofenac for acute pain osteoarthritis of hip1

54

Klein G., Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis if the hip: a double-blind, randomized study comparing oral enzymes with non-steroidal anti-inflammatory drugs. ClinExp Rheumatl. 2006 24:25-30.!

Osteoarthritis • Omega-3 fatty acids — multiple studies • Curcumin — in turmeric, many anti-inflammatory

properties • Avocado soybean unsaponifiables • Boswellia serrata

– Decreases leukotriene synthesis – Prospective randomized study compared Boswellia to

valdecoxib, osteoarthritis of the knee1

• 400 mg/day Boswellia vs valdecoxib 10 mg/day • Boswellia slower onset (2 months), as effective, effect persisted

• Ginger — knee study2

55

1.  Sontakke S., et al., Indian J Pharmacology. 2007;39(1):27-29.!2.  Altman R., et al., Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum

2001 44:25312538.!

Myofascial Pain Syndrome

• Referred by free nerve endings between layers and strings of fascia sensing pressure and shear deformation

• Worst pain is referred by trigger point, where free unmyelinated nerve endings are under the most pressure from fascia

56

Sensory Nerves in Myofascial Tissue

• Tibial nerve – 3x more sensory fibers than motor fibers

• 20% originate in mechanoreceptors—Golgi organs, Pacini corpuscles, Ruffini endings

• 80% small diameter interstitial muscle/fascia receptors – 90% unmyelinated free nerve endings

» some for pain, thermo/chemoception » majority for mechanical tension/pressure

• Anatomy studies demonstrate most sensory nerve input is from unmyelinated free nerve endings between fibers of fascia, mostly measuring mechanical tension, shear, and pressure

57

Mitchell & Schmitt, In: Shepherd JT et al. (eds). Handbook of Physiology, Sect. 2, Vol. III, 1977.

Fascia Shear

• Generally accepted that myofascial pain comes from myofascial trigger points in muscle and fascia (Travell Simons Diagrams)

58

Myofascial Pain Syndrome • Magnesium — muscle relaxant

– Magnesium glycinate, citrate, lactate – Oxide is most gut sensitive, helps with constipation – Measure RBC Mg, not serum Mg

• CoQ-10; D-ribose (still sugar) – Improves result of mitochondrial function

• Vitamin D • Fish oil • Malic acid • L-carnitine • Boswellia, White willow bark

59

Myofascial Pain Syndrome

• Herbs for stress • Herbs for adrenal support • Herbs for inflammation (help reduce

inflammation and pain from food)

60

Chronic Low Back Pain • Anti-inflammatory diet • Omega-3 fatty acids • Devil’s Claw (Harpagophytum procumbent

– Analgesic effect for short-term pain1

– 800 mg tid • Willow Bark

– Contains salicylates, botanical precursor to aspirin – For short-term pain2

– 240 mg salicin once daily

61

1.  Gagnier J., er al., Herbal medicine for low back pain. Cochrane Database Syst Rev. 2 2006 CD004504.!2.  IBID.!

Neck Pain • Omega-3 Fatty Acids • Anti-inflammatory diet • Antioxidants

– Fruits, colored vegetables, vitamin E • Turmeric • Boswellia (Frankincense) • Avocado • Willow bark • Ginger • Cat’s claw • Devil’s claw

62

Gout

• Vitamin C decreases uric acid levels (500 mg/day)1,2

• Eicosapentaenoic Acid and Gamma-Linolenic Acid (omega-6 — evening primrose, borage, black currant seed)

– Suppress inflammation in monosodium irate-induced arthropathy3

• Cherry — 2 servings 280 g, lowered plasma urate levels4

63

1.  Berger L., et al., The effect of ascorbic acid on uric acid excretion n with a commentary on the real handling of ascorbic acid. Am J Med. 1977 62:71-76.!

2.  Huang H., et al., The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial. Arthritis Rhem. 2005 52:1843-1847.!

3.  Tate G., et al., Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid. Arthritis Rheum. 1988 32:1543-1551!

4.  Jacob R, et al., Consumption of cherries lowers plasma urate in healthy women. J Nutr. 2003 133:1826-1829.!

Gout

• Bromelian • Equivalent to diclofenac for acute pain osteoarthritis of hip1

• Boswellia — anti-inflammatory2

• Celery seed — uricosuric best known2

– Improve efficacy with dandelion leaves (diuretic) • Nettle and Birch leaves2

• Salicylates block uricosuric drugs – Willow bark, meadowsweet — herbs may also2

64

1.  Klein G., et al., Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip: a double blind, randomized study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006 24:25-30.!

2.  Bone and Mills: Principles and Practice of Phytotherapy 2nd ed. Churchill Livinstron 309-310; 2013.!

Carpal Tunnel Syndrome RSI/Epicondylitis

• Consider herbs on the basis of – Inflammation

• devil’s claw, cat’s claw, Boswellia, celery seed, turmeric, ginger, willow bark, topical arnica, comfrey

– Restricted blood flow • ginkgo

– Local edema • horse chestnut, butcher’s broom

– Nerve entrapment • St John’s wort

– Fascia healing • Gotu kola (improves collage cross linking)

65 1.  Bone and Mills: Principles and Practice of Phytotherapy 2nd ed. Churchill Livinstron 311; 2013.!

• Vitamin B-6 – Rakel says no proof for benefit

• But may be helpful in patients with underlying deficiency – Deficiencies are common

• Experience with P-5-P 50 mg bid for impingement neuropathies, may be helpful, no side effects

66

Carpal Tunnel Syndrome

Rheumatology

• Fibromyalgia • Chronic fatigue syndrome • Rheumatoid arthritis •  Inflammatory bowel disease

67

Fibromyalgia /

Chronic Fatigue Syndrome

• Central Sensitivity Syndrome1

• Co-morbidity with CFS

68

1. Smith H., et. al., Fibromyalgia: an afferent processing disorder leading to a complex pain generalized syndrome. Pain Physician. 2011;14(2):E217-E245.!

Fibromyalgia /

Chronic Fatigue Syndrome • Nervine tonic herbs

– St John’s wort boosted growth hormone in small trial1

– Bacopa and Scutellaria lateriflora • Adaptogenic and adrenal supportive herbs

– Astragalus, Eleutherococcus, rhodiola, panax ginseng, withania, glycyrrhiza and rehmannia

•  Immune modulating herbs – Echinacea and Hemidesmus

• Cognition supporting2

– Ginkgo and Bacopa

69

1.  Franklin M., et. al., Neuroendocrine evidence for dopaminergic actions of hypericum extract in healthy volunteers. Bill Psychiatry. 1999;46(4):581-584.!

2.  Bone and Mills 2013.!

Fibromyalgia add…

• Anxiolytic and hypnotic herbs reduce sympathetic overactivity, improve sleep quality – Kava, Valeriana, Passiflora, Bacopa, Skullcap, Vitex,

Zizyphus spinosa, Magnolia officinalis, Crataegus, Corydalis • Anti-Inflammatory and analgesic herbs help address

disorder of central afferent processing – Rehmannia, Apium, Boswellia, Curcuma, Salix, Bupleurum

• Antidepressant herbs – Rhodiola, Hypericum, Lavandula

70 Bone and Mills 2013.!

Key Herbs for FMS

• California poppy, jamaican dogwood and corydalis for pain and sleep

• Gotu kola, grape seed, bilberry for microcirculation

• Down regulate smooth muscle reactivity – Hawthorn (Crataegus), Cramp bark, Chamomile

71

Herbal Therapies • Kava

– Enhanced mood vs placebo 250 mg 3 week RCT (Sarris J., et al., 2009 Psychopharmacology (Berl) Aug;

205(3):399-407). – Calm the nerves, erase effects of everyday tension and stress, promote relaxation and

sleep, support relief of muscular tension • Not for use by persons pregnant, not with EtOH, not for prolonged use, rare liver injury, should be extracted in water

• Gingko extract at 120 mg/day for 3 months significantly supported plasma cortisol levels during the stress caused by the glucose tolerance test in healthy volunteers1

• Rhodiola & Ginseng – Rhodiola root extract containing rosins and salidrosied and Korean Ginseng root from Panax ginseng root containing ginsenosides 2-4x/day – Enhance mental clarity and support cognitive function – Promote vitality and stamina – Maintain feelings of general well-being under temporary stress – Support and maintain the body as it ages – Support the body’s natural defenses against emotional and environmental stressors

72 1.  Kudos GB., Clin Chem 2007;53(6, Suple S):A186.!2.  Bone and Mills 2013.!

Fibromyalgia /

Chronic Fatigue Syndrome • Omega-3 fatty acids may decrease pain • Vitamin D (low levels associated with pain)1

• Magnesium citrate 300 mg/day, 8 wk RCT=> decrease tender points, sensitivity, depression2

• S-Adenosylmethionine (SAMe) may help with depression2

• D-Ribose tid for mitochondrial efficiency (still sugar-suggest only before exercise)3

• B-12 — suggest methyl or hydroxy cobalamin, can inject 1 mg daily for 3 months • Coenzyme Q-10 100-400 mg/day (mitochondrial function) • Acetyl-L-Carnitine 500 mg bid (intracellular levels typically low)4

73

1.  Straube S., et al., Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev. (1)2010!

2.  Bagis S., et al. Rheumatol Int 3013;33(1):167-172.!3.  Jacobsen S., Oral S-adenosyl methionine in primary fibromyalgia: double-blind clinical evaluation. Stand J

Rheumatol. 1991 20:294-302.!4.  Teitelbaum J., et. al., The use of d-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J

Altern Complement Med. 2006 12:857-862.!5.  Rakel 3rd Edition.!

FMS and Endocrine/Stress Response

• Dysfunctional HPA axis/stress response • Disordered sleep patterns • Fatigue

74

Other Treatment Priorities

• Balance immunity and increase NK cell function (Echinacea root, vit D, Zinc)

• Address chronic inflammation/cytokines with Turmeric, Omega-3, Rehmannia

• Persistant organisms—Echinacea root, Cat’s claw, St John’s wort, licorice

• Sympathetic dominance—Hawthorn, Horsechestnut 75

Other Treatment Priorities

•  Improve mitochondrial function (Hawthorn, Mg • Cytoprotection—Nrf2/ARE herbs include

echinacea root, adaptogens, glutathione, whey – Vital HSP (heat shock protein) responses

decreased in CFS (includes HSP267 and HSP70 • Detoxification—incr Nrf2/ARE, glutathione,

Schisandra 76 Jammes Y., et al., J Intern Med 2012;272(1):74-84.!

Other Treatment Priorities

• Balance immune system function (Echinacea root, antiallergic herbs, vitamin D, Zinc

• Chronic inflammation/cytokines (Turmeric, omega-3 FA, St John’s Wort, Licorice

• Dysbiosis – gut, flora, healing herbs

77

Not all Chocolate is Equal

78

Rheumatoid Arthritis • Essential fatty acids EPA/DHA1

• Gamma-linolenic acid (Evening primrose oil/Borage oil)2

• Conjugated Linoleic Acids – Decrease morning stiffness, ESR, 2 caps daily3

•  Antioxidants (vitamin E mixed, Vit C, Selenium)4

79

1.  Henderson C., Panush R., Diets, nutritional supplements, and nutritional therapies in rheumatic diseases. Rheum Dis Clin North Am. 1999 25:937-968.!

2.  Ernst E., Chrubasik S., Phyto-anti-inflammatories: a systemic review of randomized placebo-controlled, double-blind trials. Rheum Dis Clin North Am. 2000 26:13-27.!

3.  Arylaeian N., et. al., Effect of conjugated linoleic acids, vitamin E and their combinations on the clinical outcome of Iranian adults with active rheumatoid arthritis. Int J Rheum Dis. 2009 12:20-28.!

4.  Rakel D., Integrative Medicine 3rd ed.!

Rheumatoid Arthritis • Andrographis • Licorice (Glycyrrhiza glabra L.)

– Treatment of corticosteroid dependency1

• Ginger inhibits inflammatory prostaglandins2

• Turmeric similar to NSAIDs3

80

1.  Bone and Mills 2013.!2.  Sirivastava L., et. al., Ginger (Zingiber officinale) and rheumatic disorders. Med Hypotheses 1989 29:25-28.!3.  Deodhar S., et. al., Preliminary studies on anti rheumatic activity of curcumin (deferaloyl methane). Indian J Med

Res. 1980 71:632-634.!

Substance Abuse

• Drugs • Tobacco • Food

81

Alcoholism

• Kudzu, traditional Chinese herb for “anti-inebriation” treatment1

• Valerian: for anxiety • St. John’s wort: for depression, several

studies show decreased alcohol intake2

• Kava kava: for anxiety

82

1.  Xie C., et. al., Diadzin, an antioxidant isoflavonoid, decreases blood alcohol levels and shortens sleep time induced by ethanol intoxication. Alcohol Clin Exp Res. 1994 18:1443-1447.!

2.  Rezvani A., et. al., Alcohol Clin Exp Res. 1988;22(3,suppl):121A.!

Addiction — Efficacy in Experience

• Treat all addictions at the same time – Drugs

• Suboxone for opiate substitution • Not the 12 step program for everyone • Methadone not a safe drug, but cheap, effective

– Tobacco – Food

• Coach away from addictive “do not eat” list – wheat, sugar, potato, fruit juice, artificial sweetener, hydrogenated fat

• Brain – Polarity Therapy

83

Tobacco

• 3 Primary Addictions – Hands,activity – Nicotine – Chemicals in tobacco

• Path – Start to roll own, organic pipe tobacco, filters,

papers, rolling machine – 2 months, progress to e-cig – Only smoke outside, and not in car

84

Thank You

End

85