Vitamins & Supplements:

12/4/2012 Outline Vitamins & Supplements: Evidence & Essentials Annual Review in Family Medicine 2012 Kevin Barrows, MD Medical Director Osher Cente...
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12/4/2012

Outline

Vitamins & Supplements: Evidence & Essentials Annual Review in Family Medicine 2012 Kevin Barrows, MD Medical Director Osher Center for Integrative Medicine UCSF School of Medicine

A.

Vitamins

B.

Herbs & Supplements - Fish Oil - Cranberry - St. John’s Wort

C.

Botanical ID Quiz

A. Vitamins

Good Food • • • •

Mediterranean Diet DASH Diet Vegetarian Fish, Olive oil, Garlic, Nuts, Oats, Soy, Alcohol, Red Wine, Purple Grape Juice, Tea, Chocolate

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Vitamin A • • • •

Avoid excess Beta-carotene vs. preformed Vit A (retinol) Safe upper limit 10,000 IU/d Relevant literature – ?increased lung cancer ?prostate cancer – No CVD primary prevention benefit – No colorectal adenoma prevention benefit

Vitamin C • Safe • No benefit of supplementation for cancer or CVD • ?common cold • dose

B Vitamins • Safe – B6 less than 50mg/d

• Homocysteine reduction – B vitamin supplementation does not reduce CVD

• Folate – Prevention of neural tube defects

Vitamin D • Deficiency is common • Goal 800 IU/d (sunlight, diet and/or supp) • Many observational studies, few RCT’s – Osteoporosis – Falls

• UL = 4,000 IU/d • D3 vs. D2 • Infants

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Vitamin E • No evidence that supplementation helps prevent cancer, CVD • Meta-analysis ↑ mortality > 400 IU/d • Unresolved issues • Fat malabsorption

Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Ann Intern Med. 2005 Jan 4;142(1):37-46

When to check: • Inadequate Intake – Dietary extremes – Recent immigrants – Poor – Elderly – Mentally ill – Eating Disorders – Alcoholism/Substance Abuse

When to check: • Abnormal GI Structure – Bariatric surgery – Other GI surgery

• Abnormal GI Function – IBD – Cystic fibrosis – Celiac – Malabsorption

When to check: • Drug-induced depletions – Metformin – PPI’s – Furosemide – Isoniazid

• Chronic Kidney Disease

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B. Herbs & Supplements Format: • Indications • Mechanisms • Evidence • Side effects • Recommendations

Fish Oil b. Mechanisms: i. TG levels ii. inflammation iii. blood pressure iv. platelet inhibition (ad + agg) v. dysrhythmias vi. atherosclerotic plaque formation vii. improvements in arterial and endothelial function

Fish Oil a. indications: - hypertriglyceridemia - 2°CHD prevention - 1°CHD prevention - HTN - CHF ---------- inflammatory diseases (RA, SLE, IBD, etc.), other (dysmenorrhea, Raynaud’s, etc.) - mental health

Fish Oil c. Evidence (hypertriglyceridemia): - dozens of trials - unanimous benefit (20-50% lowering) - 2-4 g/d of ω-3 - AHA recommended - FDA-approved Lovaza® Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta analysis. Eslick GD, Howe PR, Smith C, Priest R, Bensoussan A. Int J Cardiol. 2009 Jul 24;136(1):4-16.

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Fish Oil c. Evidence ( 2°CHD): - Dozens of RCT’s, including 10,000’s patients - 1999 GISSI-Prevenzione (n=11,000) Shows large reduction: 1) in sudden cardiac death 2) total cardiovascular mortality 3) overall mortality •

Fish Oil c. Evidence ( 2°CHD): negative studies in the last two years - two RCT add-on to modern full usual care •

OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Rauch B, et al, OMEGA Study Group. Circulation. 2010 Nov 23;122(21):2152-9.



n-3 fatty acids and cardiovascular events after myocardial infarction. Kromhout D, et al Alpha Omega Trial Group. N Engl J Med. 2010 Nov 18;363(21):2015-26

GISSI was not placebo-controlled and dropout rate 25%

Fish Oil • Two meta-analyses •

Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials.,Kwak SM, et al, Korean Meta-analysis Study Group. Arch Intern Med. 2012 May 14;172(9):686-94



Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. JAMA. 2012 Sep 12;308(10):1024-33.

Fish Oil c. Evidence ( 1°CHD): - 4 RCT’s, >25 prospective cohort studies, 7 case control studies - n= 100,000’s (JELIS) - overall positive, but some studies negative •

Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Yokoyama M, et al, Japan EPA lipid intervention study (JELIS) Investigators Lancet. 2007 Mar 31;369(9567):1090-8

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Fish Oil c. Evidence (HTN):

Fish Oil c. Evidence (CHF): 2008 GISSI – Heart Failure (n= 6,975)

- 3 meta-analyses (largest n=36 RCT’s)

1) reduced CV hosp

- “fish oil supplementation, especially at higher doses, significantly lowers blood pressure”

2) reduced all-cause mortality

- SBP 3-6 mm Hg and DBP 2-4 mm Hg • •

Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. Geleijnse JM; Giltay EJ; Grobbee DE; Donders AR; Kok FJ J Hypertens 2002 Aug;20(8):1493-9

Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Gissi-HF Investigators, Lancet. 2008 Oct 4;372(9645):1223-30.

Fish Oil

Fish Oil c. Evidence (CHF): - two other RCT’s 1) TNF-alpha and maintain bodyweight 2) increased endothelium-dependent vasodilation

d. Side Effects: – “fishy burp”, halitosis, heartburn, dyspepsia, nausea, loose stools – Increase LDL because larger particles – Small increase HDL – Cod liver oil risk of hypervitaminosis A – Risk of bleeding with anticoagulants overstated (no problem up to 3g/d) – ? benefit for patients with ICD’s

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Fish Oil

e. Recommendations:

d. Side Effects: -

Contamination -

-

Fish Oil

Mercury PCB’s

Most brands meet govt. standards for safety (ConsumerLab.com) Some brands have independent 3rd party testing as part of their process

1) Dose by EPA + DHA a) Hypertriglyceridemia 2-4 g/d b) 1°and 2°prevention CHD 1 g/d c) CHF 1 g/d d) HTN 3 g/d trial x 3-4 months 2) 1g/d choose more concentrated.

Fish Oil

St. John’s Wort

3) Palatability: capsules vs. oil, brand, flavor, before meal, freeze the capsules 4) Vegetarian options - flax seed, etc. ALA conversion problem - algae (DHA predominant, e.g. Martek®, V-Pure®, Ovega-3®)

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St. John’s Wort – Hypericum perforatum – perennial herb – 1 to 3 feet in uncultivated ground, woods, hedges, roadsides and meadows – native to Europe – naturalized to North America – one of the oldest medicinal herbs of Europe – traditional uses

St. John’s Wort b. Mechanisms: - serotonin - norepinephrine - dopamine

St. John’s Wort a. indications: - depression - somatoform disorders

St. John’s Wort c. Evidence (depression): - >60 RCT’s - 2008 Cochrane Review 1) more effective than placebo 2) equal efficacy to pharmaceutical antidepressants 3) fewer side effects than pharmaceuticals St. John’s wort for depression, Linde K, et al, Cochrane Database Syst Rev. 2008;(4):CD000448

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St. John’s Wort c. Evidence (depression): Head-to-head Trials vs. SSRI’s 1) SJW vs. citalopram (RCT, n=388) >>> equal efficacy 2) SJW vs. paroxetine “non-inferiority”(RCT, n=251) >>> SJW (57%) and paroxetine (45%) 3) SJW vs. fluoxetine (DBRCT, n=240) >>> SJW greater efficacy, fewer side effects 4) SJW vs. sertraline (DBRCT, n= 340) >>> neither SJW nor sertraline more effective than placebo

St. John’s Wort c. Evidence (somatoform d/o’s): - 2 DBPC RCT’s (n=151, n= 184) - both show large benefit over placebo with high statistical significance Treatment of somatoform disorders with St. John's wort: a randomized, doubleblind and placebo-controlled trial. Müller T, Mannel M, Murck H, Rahlfs VW. Psychosom Med. 2004 Jul-Aug;66(4):538-47. St John's wort extract (LI 160) in somatoform disorders: results of a placebocontrolled trial. Volz HP, Murck H, Kasper S, Möller HJ. Psychopharmacology (Berl). 2002 Nov;164(3):294-300.

St. John’s Wort •







Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Gastpar M, Singer A, Zeller K., Pharmacopsychiatry. 2006 Mar;39(2):66-75. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a metaanalysis. Rahimi R, Nikfar S, Abdollahi M., Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. Szegedi A, Kohnen R, Dienel A, Kieser M., BMJ. 2005 Mar 5;330(7490):503. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. Hypericum Depression Trial Study Group., JAMA. 2002 Apr 10;287(14):1807-14.

St. John’s Wort d. Side Effects: i. well-tolerated ii. photosensitivity iii. mild headache iv. restlessness v. case reports of withdrawal sxs vi. Herb-drug interactions

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St. John’s Wort Herb-drug interactions - SJW is potent inducer of cytochrome P450 system (isozyme CYP3A4) - may lower the blood levels of medications that are metabolized by this system (eg, alprazolam, ethinyl estradiol, warfarin, cyclosporine, statins, indinavir) - Wean off 5d before surgery (due to risk of interactions with peri-operative meds)

St. John’s Wort Pregnancy & Lactation • Insufficient data • Pregnancy – No clear evidence of risk in animals or humans • Lactation – Very little excreted into breast milk

- Do not combine with pharmaceutical SSRI’s due to risk of serotonin syndrome

St. John’s Wort e. Recommendations: 1) Good choice for mild-moderate depression (maybe for somatoform d/o’s) 2) Dose 300 mg tid of preparation standardized 0.3% hypericin or 2-3% hyperforin content (made from flowers and stems) 3) Check for herb-drug interactions

St. John’s Wort Approved products: • Gaia Herbs • New Chapter • Kira • Puritan’s Pride • Sundown • 21st Century • Nature’s Resource

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Cranberry Vaccinium macrocarpon

Cranberry a. indications: - preventing UTI

Cranberry b. Mechanism: - proanthocyanidins interfere with bacterial adhesion to the urinary tract epithelial cells - irreversible binding to P-fimbria of E. coli

Cranberry c. Evidence: 2012 Review & Meta-analysis (n=13 RCT’s) - RR for users vs nonusers was 0.62 (95% CI, 0.490.80)

- Juice more effective than capsules? - Better b.i.d. or more frequent - “substantial heterogeneity across trials” Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. Wang CH, et al, Arch Intern Med. 2012 Jul 9;172(13):988-96

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Cranberry c. Evidence: -

2009 Cochrane Review (n=10 RCT’s) 1) “CJ may decrease the number of symptomatic UTIs, particularly for women with recurrent UTIs” 2) “It’s effectiveness for other groups is less certain” 3) “large number of dropouts”

Cranberry d. Side Effects: - GI upset (at high dose, 3-4 l/d juice) - glycemic load for diabetics (from sweetened juice) - theoretical risk of oxalate stone recurrence if long-term use - avoid in ASA-allergic patients

Cranberries for preventing urinary tract infections Jepson RG, et al Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001321

Cranberry e. Recommendations: -

Dose = 26% cranberry juice, 300-480 mL daily = 15-30 ml of 100% juice

-

Other forms: frozen probably fine >>> 100% juice >>> dried cranberries >>> 26% juice

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Capsules probably a good alternative: 400 mg twice daily

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Reducing urinary odor (inadequate data) (1/3 dose)

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