Phytomedicine 2.0

Botanical Medicine in Clinical Practice

Aviva Romm, MD

Learning Objectives

Upon completion of this session, participants will be better able to:

1. Describe the role of botanical medicines as part of the continuum of “food as medicine.”

2. Be familiar with a selection of evidence-based phytomedicines for intestinal hyperpermeability, GERD, insulin resistance, dyslipidemia, and as anti-inflammatory agents.

3. Integrate evidence-based botanical medicines into an overall integrative treatment plan.

Food or Medicine?

It’s a Continuum

Food Herbs/Spices Herbal Medicine

Botanical Safety

Safe Medicine?

Case Study 1: JRA

Katie is 2 years old

Diagnosed with polyarticular JRA use by rheumatologist at 18 mo. old

Chronic pain, chronic NSAID use, regular steroid injections

Symptoms began after chronic NSAID and PPI use

Rheumatologist wants to begin methotrexate

Mom, an RN, is seeking alternatives

What’s Going On?

History

PMH

Born by NSVD, mother on insulin for poorly controlled GDM, then IDDM postpartum.

Live rurally + pesticide exposure, + heavy metal contamination, ? arsenic exposure

Antibiotic use history

Eczema

Gastritis

Mother is gluten intolerant

Nutrition Review

Picky eater

Hx low vitamin 25 OH-D

Evaluation/ Testing

Lyme (WB + ELISA, coinfx) negative

EBV negative

Celiac HLA, Gluten Abs negative

MTHFR +/-

Urine toxic metals elevated lead body burden

Iron deficiency anemia

Stool testing + roundworm, tx.

Detox studies low GSH

General Initial

Approach

Elimination diet Anti-inflammatory diet (including extended GF/DF)

4R program for gut hyper permeability

Anti-inflammatory botanicals

Observe for flare triggers

Reduce environmental toxin exposures

4 R Program

Remove: Triggers and irritants

Repair: Provide nutrients that nourish and heal the intestinal membranes and healthy flora. Consider L-glutamine, aloe vera gel, licorice root extract (or DGL), marshmallow root, zinc, and larch arabinogalactan.

Replace: Digestive enzymes and hydrochloric acid, for example, are replaced in this phase.

Reinoculate: Prebiotics and probiotics, along with good quality fiber

Supplements

Multivitamin

Omega 3 fats twice daily

Licorice root extract, marshmallow root, chamomile, ginger in powdered and liquid extract forms in foods

Meriva form of curcumin, 500 mg BID

Vitamin D3 2000 units/day

L-Glutamine 2.5 g twice daily

Infant Formula Probiotic

GSH topically

Licorice Traditional uses: cough, colds, sore throat, GERD,

gastritis, IBD Compounds in licorice increase local prostaglandin

levels that promote mucus secretion and cell proliferation in the stomach

Preparations without glycyrrhizin are called DGL

Dose 700-800 mg (760 mg) Chewable tablets

Safety Avoid in pts with HTN, hyperaldo (risk of hypoK), on

steroids Likely safe in healthy adults when used at doses not

exceeding 3 grams/d for periods up to 3-4 weeks. Avoid licorice in pregnancy, DGL likely ok

Chamomile

Traditionally widely used

Evidence based uses include: Colic (w/fennel, lemon balm) Pediatric “stomach aches” Diarrhea (w/apple pectin) Dyspepsia (in Iberogast) Oral mucositis Anxiety/GAD

Dose 1 ml TID (less for pediatric use)

Safety May cause allergic reaction in some individuals

(rare) w/ragweed allergy.

Turmeric What the Science Says

NIH: positive studies for UC, Crohn’s, rheumatoid d/o

In vitro and animal studies show it increases phase II enzymes and inhibits phase I CYP1A

Antioxidant effects: Down regulates COX2, LOX, NFkB, AP-1, TNF

Safety

Warfarin interaction, bleeding risk at high doses

Dose (Adult)

1200-2400 mg/d curcumin for IBD

India: average daily intake = 60 mg curcumin (2.5 gm/d of turmeric)

20 mg black pepper/1 kg curcumin -> approx. 2000% absorption increase

Ginger What the Science Says

Clinical research shows that taking ginger extracts can modestly improve pain in some patients with osteoarthritis.

May be comparable to ibuprofen in a dose of 500 mg twice daily

Also compared favorably to diclofenac + glucosamine sulfate

There is some preliminary evidence that ginger might be helpful for decreasing joint pain in patients with RA.

Dose (Adult)

250 mg ginger extract four times daily, dosing may vary according to the preparation

Marshmallow Root

Approved by the German Commission E for the treatment of oral and pharyngeal ulcers, and mild inflammation of gastric mucosa.

Potential anti-inflammatory effect based on in vitro effects on cytokines, TNF, and IL-6.

Lack of clinical research.

Considered quite safe; primary constituents are mucilage polysaccharides and flavonoids.

Treatment/Outcome

Had 1 (prescheduled) joint injection at the outset

Within 8 months no further need for NSAIDs or steroids

Per rheumatologist, methotrexate no longer indicated

Per rheumatologist, only 1 joint (index finger) remains slightly swollen compared to 8 joints before starting care

Able to run, play, dance without pain, just like other kids in family!

Case Study 2: Complex Adult

46 yo woman with:

BPAD, Anxiety, paranoia

CFIDS/ME, FM

Circadian rhythm sleep disorder

Hunger/ NES

GERD

Nausea, gastritis

SIBO

Lactose intolerance – (eats

dairy daily)

Insulin resistance

Osteopenia

Hypothyroidism

Joint pain

Dental caries

Hx hypovitaminosis D

Hx anemia

“Brain fog”

Decreased libido

FHx

Indian descent

Mother: obesity, inflammatory arthritis, dementia, depression

Father: obesity, depression

Sisters: cancer, obesity, depression, bipolar

Children: depression, ADD, SA SA (caffeine, MJ, ETOH)

Paternal Grandmother: depression

Uncles: depression

All family members, including pt., tapeworm hx

Soc Hx

Moved to US in 20s

Lives with husband, son in college – ADD on meds

Husband verbally abusive but also loving/attentive (he grew up with an abusive mother)

Financially comfortable

Stay at home mother

Family primarily in India

Meds/Allergies

Medications

Remeron for sleep-wake cycle - has also noticed increased appetite and weight gain on it

Lexapro - alternates because effectiveness goes away

Allergies: NKDA

Environmental HX

Mold growing up in India

No tuna or other fish

Composites as an adult; no fillings as a kid; 4 cavities past 4 yrs.

Household chemical exposures- lots of bleach

No other known toxic exposures

Physical Exam

Vitals

MSQ 74, BP 113/69, Ht 60, Wt 146.5, BMI 28.61, Waist Circ 36.5

Exam

Anxious, hyper speech, pleasant

Overweight, soft, doughy, “Damp”

Dark circles under eyes

Hair thin

Food Journal

Pertinent Labs

CBC: low normal Hb & Hct, Ferretin 14

NMR: HLD w/insulin resistance LDL-P 2187, LDL-C 123, HDL C-50, LDL-p 1320, Patt B, LP-IR 55

A1C 6.1

TSH initially 2.38, FT3 3.2, Iodine 38, RT3 19, neg abs, CRP 3.97

Glucose F 81, 1hr 189, 2 hr 145 (H)

Ins 1 hr 188 (H)

MTHFR A1298C +/+

Hcy 6.7

Vitamin D deficiency

Iodine low

Functional

Detoxification issues on ION

4+ yeast, SIBO, Leaky gut

Sl . Depressed AM cortisol w/H nl MN

Hg 20 on ION (post); Bismuth H

Leaky Gut

K.R. Functional Medicine Matrix

K.R. Initial Treatment

Plan

Mind Body Strategy Options: Select 2

15 minutes of breathing/relaxation exercises per day.

Biofeedback with Heart Math

Audiotapes - available on line to listen to before bed.

Biofeedback.

Do something for yourself everyday.

Take a warm bath several nights each week with 1 cup of Epsom salts and 5-7 drops of lavender essential oil in the bath for relaxation.

Diet

Low Glycemic/Portfolio Diet:

Low grains, eliminate white rice completely, no sugar and emphasize meats - willing to eat fish, chicken, lamb.

Dairy free

Avoid caffeine which increases anxiety and sleep problems

Exercise/ Osteopenia

Start with walking for 45 minutes 3 times/week.

Hypothyroid

Armour thyroid

CFIDS/ME, FM

Reduce inflammation and support detoxification and mitochondrial function

CoQ10

NAC

Turmeric in the form of Meriva, 2000 mg/day

A proprietary blend containing proteolytic enzymes, Boswellia, Ginger, Turmeric, Quercetin, Rosemary, and Resveratrol

Cardiometabolic Issues

Portfolio Diet

Flax seeds, olive oil, almonds, meta-sitosterol

Anemia

Iron chelate + buffered Vit C, Vitamin D 3000 u/d

Gut repair/GERD

4 R Program

Xifaxan for SIBO x 14 days

Nystatin x 30 days

Digestive Enzymes, Betaine HCL

Herbal product containing: L-Glutamine (5000 mg), Arabinogalactans (1000 mg), DGL (500 mg), Aloe Vera Leaf Extract 250 mg, Slippery Elm Bark (200 mg), Zinc Carnosine (100 mg), Marshmallow Root (100 mg)

DGL tablets, chew 2-3, 15 min before meals + before bed, PRN

Circadian rhythm sleep disorder NOS/ NES

Sleep hygiene practices

Balance blood sugar, and eating protein at meals and snacks will help. Also, we will look at your nutrition, gut flora, and for parasites to see if any of these are a contributing issue.

A proprietary blend containing B-complex, Magnesium, L-theanine, Valerian, Passionflower, Lemon balm, and Ashwagandha

A proprietary blend containing GABA (750 mg), L-tyrosine (1200 mg), Inositol (600 mg), Taurine (600 mg), 5-HTP (150 mg)

Melatonin 1-3 mg qhs

Anxiety

Lavela (lavender oil)

Bipolar affective disorder, depressed, moderate

EPA/DHA

Added in Deplin 7.5

GIFX post- treatment with 4R Plan

SIBO

What Can Happen…

Lost 25 + LBS

Said:

”I continue to feel so much better because of you”

“Anxiety has completely disappeared – the neurolink is so helpful”

“My stomach doing so well” - able to take her supplements

“Armour has helped so much” - feverish feeling resolved, sex drive returning

“Sleep is perfect”

“No joint pain”

“Mood better than [she] believed possible”

Is still tired by 5 pm

Diet - for 3 mo. was “religious” and lost so much weight. Started eating yogurt and gluten again - after a week started feeling unwell, couldn't walk properly - so went back off completely and within a week the inflammation is gone.

Summary of Lab (+) Changes

10 months into treatment:

LDL-P 1817, LDL-C 103, LDL-p 1084

A1C 5.6

Glucose F 93, 1hr 166, 2 hr. 116

Ins 1 hr. 127

Vit D 61

TSH > 5 started on Armour TSH 1.0 FT3 2.9

Hct >30 37.4

Ferritin 14 3553 after iron chelate and buffered vitamin C

Metabolic Syndrome

Flax Seeds

Actions

high fiber, anti-inflammatory, anticholesterolemic, antidiabetic, +/- reductions in breast CA, menopausal sx, mastalgia

Evidence

lignans weak phytoestrogens w/possible antiestrogenic effects

Dose

25-40 gm/day

Contraindications

Usually well-tolerated

Can significantly increase the number of bowel movements

Doses > 45 grams per day may not be tolerated for this reason

Some concern that large amounts could -> bowel obstruction; not likely to occur if consumed with adequate fluids

Olive Oil Reduced risk of CVD including risk of 1st MI by 82%

@4 TBS/day Reductions in cholesterol Modified diet including high amounts of EVOO over

6 months, with conventional treatments for hypertension, can significantly improve BP and lead to decrease doses or discontinued use of anti-hypertensives.

FDA allows olive oil and olive oil-containing food labels to state that limited evidence suggests that consuming 23 grams/day (~ TBS) of olive oil instead of saturated fats may reduce the risk of heart disease.

Lower risk of breast and colon CA associated with regular intake

Olive leaf extract taken orally can also be anti-hypertensive

Pomegranate

50 mL/day of juice leads to reduced intima-media thickness of the carotid artery by up to 35% after one year.

Drinking concentrated pomegranate juice 40 grams/day can significantly reduce total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with hyperlipidemia and DM2.

Drinking pomegranate juice 50 mL/day for up to 1 year can reduce systolic blood pressure by 5% to 21%

POM Wonderful 240 mL daily for 3 months decreases stress-induced myocardial ischemia in patients with coronary heart disease.

Cinnamon 1, 3, or 6 g daily for 40 days lowered

fasting serum glucose by 18% to 29%, triglycerides by 23% to 30%, low-density lipoprotein (LDL) by 7% to 27%, and total Chol by 12% to 26% in pts. with type 2 diabetes

MA of 8 trials demonstrates that cinnamon reduces blood sugar modestly but effectively in DM2 pts

3 studies found no significant effect on blood glucose, HbA1C, Chol, or triglycerides when used in doses of 1-3 g daily up to 4 months

Hypoglycemic activity comparable to metformin

MA of 5 trials failed to identify improvement in 5 parameters including FBG, A1C

Safety

Overall safe, caution w/other DM meds

Milk thistle

Actions

Decreases insulin resistance, hepatoprotective, potent impacts on Phase I and Phase II detoxification, decreased NFK-b, COX-2, increased GSH, inflamm leukotrienese

Dose

200 mg TID stand. to 80% silymarin

Contraindications: n/a

45

Depression and Anxiety

St. John’s Wort Cochrane 2008: 29 RCTs on various preparations in MA. N = total

of 5489 patients

18 RCTs compared SJW w/ placebo; 17 RCTs compared SJW w/ Rx drugs

Superior to placebo in patients with major depression; similarly effective as standard antidepressants; fewer side effects than standard ADS.

Dose

Products standardized to 0.3% hypericin and/or 3-5% hyperforin

300-600 mg TID

Safety

Induces CYP3A4 subset of P-450 enzymes that metabolize many pharmaceuticals

Interacts with P- glycoprotein

Potential H-D interactions include warfarin, digoxin, cyclosporine, indinavir, irinotecan, and OCPs

Rhodiola

“Adaptogen”

Preliminary data suggests efficacy in the tx of GAD

Also helpful with stress, memory, and fatigue

Studies done in military cadets, college students, night shift workers

Dose

Clinical trials use products containing 2-3% rosavin and 0.8-1% salidroside.

Dose 100mg-400mg/day

Safety

Overall high safety profile

Care should be taken with BPAD

Lavender Promising data using oil extract for tx of

generalized and test anxiety

Study of a proprietary product showed effects comparable to lorazapam in the tx of anxiety based on HAM-A and SAS scores

Alleviates anxiety related sleep disturbance and improves sleep quality

Dose

Per package, typically 1 gel cap qhs

Safety

No sedative effects

No addictive or abuse potential

Kava kava Anxiety: Most evidence shows extracts

standardized to 70% kavalactones superior to placebo, and possibly comparable to low-dose benzodiazepines.

Most clinical studies have used the standardized extract WS 1490 (Schwabe), standardized to contain 70% kava-lactones (also known as kavapyrones). This extract is more than 2x as concentrated as most commercially available products.

Some evidence that upwardly titrating kava over 1 week while tapering benzodiazepine over 2 weeks can prevent withdrawal symptoms in some people with non-psychotic anxiety.

Kava kava (cont.)

• 2 small trials have shown that kava standardized to 15% or 70% kava-lactones is superior to placebo taken orally for short-term treatment of neurovegetative and anxiety symptoms related to climacteric. Significant improvement occurred after one week of treatment.

• Preliminary clinical research in healthy volunteers suggests that taking kava orally might reduce physiological reactivity during stressful situations.

Dose

• For anxiety disorders, most clinical trials have used kava extract standardized to 70% kava-lactone content. Doses of the kava extract were most commonly 100 mg (70 mg kava-lactones) three times daily

• Treatment for 1-8 weeks may be necessary for significant improvement though acute reductions in anxiety are possible

Safety

• Realistic concerns regarding hepatotoxicity, though rare occurrence given frequency of use globally.

• Unpredictability is the challenge.

• Check LFTs q. 6 weeks (no data on timing)

Key Clinical Take Home Points

1.The use of plant medicines (foods, botanicals) as alternatives to pharmaceuticals is not simply an ideological approach - it is a sound and important public health approach in the face of existing environmental and human costs of pharmaceutical overuse.

2.Botanicals have demonstrated safety and efficacy, some comparing even favorably to pharmaceuticals, in the treatment of common acute and common health problems.

3.Reliable resources are available for learning about and applying botanicals in clinical practice so that you can begin to safely and effectively integrate them into practice whether as foods or supplements.

Want to Learn (MUCH) More?

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References

Chamomile

McKay DL, Blumberg JB. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res. 2006 Jul;20(7):519-30.

Ross SM. Generalized anxiety disorder (GAD): efficacy of standardized Matricaria recutita (German chamomile) extract in the treatment of generalized anxiety disorder. Holist Nurs Pract. 2013 Nov-Dec;27(6):366-8.

Srivastava JK, Shankar E, and Gupta S. Chamomile: A herbal medicine of the past with bright future. Mol Med Report. Nov 1, 2010; 3(6): 895–901.

Cinnamon

Baker WL, Gutierrez-Williams G, et al. Effect of cinnamon on glucose control and lipid parameters. Diabetes Care. 2008;31:41-3.

Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med. 2009;22:507-12.

Khan A, Safdar M, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215-8.

Curcumin/Turmeric

Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res 2012;26:1719-25.

Taylor RA, Leonard MC. Curcumin for inflammatory bowel disease: a review of human studies. Altern Med Rev. 2011 Jun;16(2):152-6.

Thapliyal R, Deshpande SS, Maru GB. Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts. Cancer Lett 2002;175:79-88.

Flaxseed

Brooks JD, Ward WE, Lewis JE, et al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004;79:318-25

Herbs At A Glance: Flaxseed and Flaxseed Oil, Accessed at http://nccam.nih.gov/health/flaxseed/ataglance.htm

Pan A, Yu D, et al. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr. 2009 Aug;90(2):288-9

Garlic

Ackermann RT, et al. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med. 2001; 161: 813-24.

Ried K, Frank OR, Stocks NP, Fakler P, Sullivan T. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008;8:13.

Silagy C, et al. A meta-analysis of the effect of garlic on blood pressure. JR Coll Phys. London 1994; 28:2-8.

Warshafsky S, et al. Effect of garlic on total semm cholesterol. A meta-analysis. Ann Int Med. 1993; 19:599-605.

Ginger

Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum. 2001 Nov;44(11):2531-8.

Srivastava K. C, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypotheses. 1992;39(4):342–8

Kava Kava

Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J. 2010 Oct 7;9:42.

Sarris J, Stough C, et al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8.

Sarris J, Kavanagh DJ, et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl). 2009 Aug;205(3):399-407.

Lavender

Kasper S, Gastpar M, et al. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol. 2010 Sep;25(5):277-87.

Licorice (DGL)

Morgan AG, Pacsoo C, McAdam WA. Maintenance therapy: a two year comparison between Caved-S and cimetidine treatment in the prevention of symptomatic gastric ulcer recurrence. Gut. 1985; 26)6):599-602.

Ruetzler K, Fleck M, et al. A randomized, double-blind comparison of licorice versus sugar-water gargle for prevention of postoperative sore throat and postextubation coughing. Anesth Analg. 2013 Sep;117(3):614-21.

Milk Thistle

Rambaldi A, et al. Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic cochrane hepato-biliary group review with meta-analyses of randomized clinical trials. Am J Gastroenterol. 2005; 100(11):2583-91.

Olive Oil

Bendinelli B, Masala G, Saieva C, et al. Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: the EPICOR Study. Am J Clin Nutr, 2011 (93):275–283.

Ros E, Martínez-González MA, et al. Mediterranean diet and cardiovascular health: Teachings of the PREDIMED study. Adv Nutr. 2014 May 14;5(3):330S-6S.

Peppermint Oil

Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337:a2313.

Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014 Jul;48(6):505-12.

Pomegranate

Hamoud S, Hayek T, et al. Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study. Atherosclerosis. 2014 Jan;232(1):204-10.

Zarfeshany A, Asgary S, Javanmard SH. Potent health effects of pomegranate. Adv Biomed Res. 2014 Mar 25;3:100.

Rhodiola

Bystritsky A, Kerwin L, Feusner JD. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety

Hung SK, Perry R, Ernst E. The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials. Phytomedicine. February 15, 2011;18(4):235-244.

St John’s wort

Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD000448.