Herbs Recommendations

Supporter
Evidence-Based Recommendations for Herbal and Dietary Supplements

Bella H. Mehta, PharmD, FAPhA The Ohio State University Tommy Johnson, PharmD, BC-ADM, CDE, FAADE Presbyterian College School of Pharmacy
Procter and Gamble
Disclosures
Tommy Johnson declares no conflicts of interest, real or
apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria Bella Mehta is on the speakers bureau for Amerisource Bergen and Cardinal Health and is a stockholder for Pfizer
Target Audience: Pharmacists ACPE#: 0202-0000-13-017-L04-P Activity Type: Knowledge-based
The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. 4
Learning Objectives
At the completion of this activity, participants will be
able to:
Summarize federal regulations governing dietary supplements Identify dietary supplements that can be recommended based on available evidence, as well as dietary supplements whose safety and efficacy are not supported by available evidence List adverse effects, clinically important drug interactions, and other cautions associated with commonly used dietary supplements Outline a strategy for guiding patient selection and use of dietary supplements Provide examples of reputable sources of evidencebased information about dietary supplements
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Which of the following regulations requires manufacturers to report serious adverse effects of herbs and dietary supplements?
A. Dietary Supplement Health and Education Act of 1994 B. Federal Food Drug and Cosmetic Act C. Dietary Supplement and Nonprescription Consumer Protection Act D. Kefauver Harris Amendment
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2013 by the American Pharmacists Association. All rights reserved.
A patient with dyslipidemia wants to start omega-3 fatty acids. His profile shows elevated LDL, elevated triglycerides and at goal HDL. Which of the following doses of omega-3 fatty acids would you tell him is most effective for him to reach target lipid goals?
What Vitamin is fat soluble, necessary for proper eye function and may increase bone fractures if taken in excess?
A. 1 gram per day B. 4 grams per day C. More is better so he

should take as much as he can tolerate D. None of the above, omega-3 fatty acids will not be beneficial for this patient
A.Vitamin A B.Vitamin B1 C.Vitamin C D.Vitamin D3
What is a reputable resource for finding information about the uses, doses and potential side effects of herbs, vitamins and supplements?
Do you currently use herbs and/or dietary supplements?
A. National Inquirer B. Natural Standard C. Vitamin Kingdom D. Happy Hempster

Health Highlights
1. Yes 2. No
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Background
Three-fourths of world relies on natural medicines JAMA study1
1990 - 34% used > 1 alternative therapy 1997 - 42% used > 1 alternative therapy
Trends in Consumer Use of Herbs/Dietary Supplements

In 2007: CDC survey reported 17.7% of Americans
used a natural product in the previous 12 months
According to the 2007 CDC survey, use of CAM

was most prevalent in:
Women Adults ages 30-69 years Patients with higher level of education Patients that are not poor Adults that were hospitalized in the past year Children whose parents used CAM
Current use approximately 40-62%2,3 $34 billion spent out of pocket annually on CAM3
Products, classes, visits to providers
$15 billion spent on herbs and dietary supplements3 29,635 supplement-related health problems
reported to poison control centers in 20094
1.Eisenberg et al. JAMA 1998;280:1569-75. 2.Barnes PM et. CDC Advance Data from Vital and Health Statistics No 343; May 2004 3.Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2004. 12 4.Clinical Toxicology Dec 2010, Vol. 48, No. 10: 9791178.
Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2008
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Popular Herbs and Dietary Supplements: 2007 National Health Survey

Fish oils/omega-3 Fatty acids Glucosamine Echinacea Flaxseed Ginseng Combination pills Gingko biloba Chondroitin Garlic Coenzyme Q10 Fiber/psyllium Green tea pills Cranberry pills Saw palmetto Soy Melatonin Grape seed extract Methylsulfonylmethane (MSM) Milk thistle Lutein
Trends in Consumer Use of Herbs/Dietary Supplements

2011 Harvard Opinion Research Program
Conducted telephone survey of 1579 respondents Approximately 4 out of 10 Americans reported using supplements in past 2 years Reasons for use:
To feel better To improve overall energy levels To boost immune system
36% had not told physician about use of supplements 5% had been told by physician or nurse to stop supplement 25% reported that they would stop using supplement if public health authorities found it was ineffective
14 15 Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311
Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2008
Popular Herbs and Dietary Supplements: 2011 Harvard Survey

Fish oils or omega-3 supplements Herbal supplements like ginseng Probiotics like acidophilus Any other supplements like amino acids, algae derivatives or combination products Supplements derived from foods like garlic supplements
REGULATIONS OF HERBS AND DIETARY SUPPLEMENTS
Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311
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Regulatory Role of FDA

FDA responsible for taking action against any
unsafe dietary supplement product after it reaches the market Post-marketing responsibilities:
Monitoring safety Product Information
Labels Claims Package insert Accompanying literature
Overview of Regulations
1951: 2 classes of drugs were established
(prescription and non-prescription (OTC))
1962: Kefauver-Harris Amendment 1994: Dietary Supplement Health and Education

Act (DSHEA)
2006: Dietary Supplement and Nonprescription

Drug Consumer Protection Act
June 22, 2007: New Dietary Supplement Current

Good Manufacturing Practices (cGMPs) Final Rule Issued by FDA
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DSHEA
Signed into law on October 25, 1994 Herbal supplements, vitamins and minerals
Dietary Supplement and Nonprescription Drug Consumer Act

Passed by Congress on 12/26/06; effective
12/26/07
considered dietary supplements not drugs Dietary ingredients in supplements no longer subject to pre-marketing safety evaluations Labeling criteria
Body structure and function claims Cannot make therapeutic claims Must state not approved by FDA Must have manufacturers name and address Not required to have lot numbers, expiration dates or contraindications
Known as the Adverse Event Reports Bill (S. 3546) Amends the Federal Food Drug and Cosmetic Act
and requires manufacturers to report serious adverse events for OTC drugs and dietary supplements Requires manufacturers to submit report of adverse event within 15 business days of receipt Requires labels to have address or phone number so that patients can report serious adverse events
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Herbs and Dietary Supplements

Omega-3 fatty acids (fish oil, krill oil) Green coffee extract Raspberry ketones Butterbur Feverfew Probiotics Vitamins and Minerals
Vitamins A, C, D, and E Niacin Minerals: calcium, iron, magnesium, zinc
HERBS AND DIETARY SUPPLEMENTS
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Fish Oils (Omega-3 Fatty Acids)

Background
Can consume in diet through cold water fish that are high in omega-3 fatty acids or through other natural products like avocado or almonds (alpha-linolenic acid) Krill oil has significantly lower concentrations of omega-3 fatty acids

Summary of clinical studies
High triglycerides Reduces triglycerides by 20-50% Slight increase LDL; negligible increase in HDL Dose: 2-5 grams (EPA+DHA) per day Primary prevention of heart disease May decrease risk of coronary heart disease death by 25% in healthy patients with long term use Dose: 1 gram daily (EPA+DHA) or 1-2 servings per week Secondary prevention of heart disease Showed 15% reduction in risk of total cardiac event, nonfatal MI, and total cardiac mortality in patients who had an MI Additional studies showing 16-23% reduction in overall mortality plus reduction in MI by 20-30% Dose: 1-10 grams daily (EPA + DHA)
Uses:
High triglycerides Reduction in risk of death from heart disease Treatment of various cancers
Mechanism:
May have anti-inflammatory and blood thinning effects May have vasodilatory and anti-arrhythmic effects Constituents are omega-3 fatty acids EPA and DHA May prevent weight loss of cancer and may slow cancer growth
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Currently some controversies about
cardioprotection

American Heart Association Recommendations
Patient
Patient with no coronary heart disease (CHD) Patient with documented CHD
Meta-analysis of 20 studies on omega-3 fatty acids

2012 JAMA1 Found no statistical significance in all-cause mortality
Recommendation
Eat a variety of fish 2 times per week; include alpha-linolenic acid foods in diet Consume 1 gram of EPA + DHA per day through food sources or supplement (with doctor) Take 2-4 grams per day of EPA + DHA through supplements in consultation with doctor 27
OPERA trial and FORWARD trial 2,3 Considerations of older vs. newer studies:
Patient populations Utilization of lipid lowering medications Overall knowledge about lifestyle changes
1. 2. 3. Rizos EC et al. JAMA. 2012;308(10):1024-1033 Marchioli et al. JAMA. 2012;308(19):2001-2011. Macchia et al. J Am Coll Cardiol. 2013 Jan 29;61(4):463-8
Patient with high triglycerides
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Adapted from table 5: Kris-Etherton et al. Circulation 2002; 106;2747-2757.

Other uses for omega-3 fatty acids:
Prevention of restonsis from angioplasty Asthma Heart failure Stroke
At high doses can increase risk
Example Fish Oils (Omega-3 Fatty Acids) Label
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Lovaza (formerly Omacor )
FDA approved omega-3 fatty acid Indicated as adjunct treatment to diet for treatment of hypertriglyceridemia Most effective with TG >500mg/dL Contains 465mg EPA and 375mg DHA in 1 gram capsule Dose: 4 grams daily

Important Adverse Effects
Fishy aftertaste Diarrhea, flatulence, belching Risk of stroke with high dose (> 46 grams/day)
Patient counseling suggestions to minimize adverse

effects:
Consider using enteric coated formulations Start at low dose and titrate up over several weeks Counsel pregnant patients and young children to limit consumption of fish oils
12 ounces per week for pregnant patients 2 ounces per week for young children
Vascepa (icosapent ethyl)

FDA approved omega-3 fatty acid soon to be on market Indicated as adjunct treatment to diet for treatment of hypertriglyceridemia 30 Most effective with TG >500mg/dL
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Important Drug Interactions
Contraceptives may decrease the triglyceride lowering effect of fish oils May increase risk of bleeding with antiplatelets and anticoagulants with high dose fish oils Orlistat decreases absorption of fish oils
Fish Oils (Omega-3 Fatty Acids) Summary

Included within American Heart Association
guidelines as potentially beneficial for:
Triglyceride lowering Preventing cardiac events in healthy patients Decreasing risk of total cardiac events, second MI and total cardiac mortality in patients that have had an MI
Titrate the dose increase slowly FDA approved product is available
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Patient Case #1
Which product will you recommend?
One of your regular patients is in the herbs and vitamins aisle and is holding 2 bottles in his hand one is EcoKrill tablets (EPA 65mg,DHA 35mg, other omega-3) and the other bottle is Iceland Health Omega Ultimate (EPA 400mg and DHA 300mg). He wants to know what you would recommend that he take. You take out his chart and see the following: Medications: Altace (ramipril) 5mg once daily, Zocor (simvastatin) 40mg once every evening, Aspirin 325mg once daily, Coumadin (warfarin) 5mg once daily Past Medical History: HTN x 5 years (at goal), Hyperlipidemia x 5 years (at goal); Atrial fibrillation x 2 years (INR at goal) Family History: Brother had a heart attack at age 40 years; Father died of heart attack at 82 years old
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1. EcoKrill 2. Iceland Health

Omega Ultimate
3. Neither would help

him
What would be the recommended dose?
Key points
This patient has lipid profile at goal and has a
strong family history of cardiac disease but has not had an event himself Select cardioprotective dose of fish oils vs. triglyceride lowering dose Could also educate about dietary sources of fish oils vs. supplements
1. 1 gram daily 2. 4 grams daily 3. As much as he

can tolerate
4. None of the
above would not recommend
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Green Coffee Extract

Background
Dr. Ozs Green Coffee Bean Project Uses Weight loss Cardiovascular conditions including high blood pressure Type 2 Diabetes Infections Mechanism Coffee beans that are not roasted so higher in chlorogenic acid Thought to have modulating effects on glucose metabolism Thought to inhibit fat accumulation Thought to have antihypertensive effect
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Summary of Clinical Studies
Weight loss
GCA extract of 700mg or 1050mg showed 1.5-2kg weight loss over 6 weeks Svetol extract showed 2.5kg weight loss vs. placebo
Hypertension
Svetol extract reduced systolic blood pressure by 5-6 mmHg and diastolic blood pressure by 3-4 mmHg
Dr. Oz Project
100 women between 35-49 years old that had BMIs of 25-45 Green coffee extract 400mg three times per day vs. placebo In 2 weeks, green coffee extract lost 2 pounds vs. 1 pound on placebo
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Major Adverse Effects
Well tolerated with no adverse effects in clinical trials Theoretical effects would those related to caffeine
Insomnia, diuresis, gastric distress, headache, anxiety, agitation
Raspberry Ketones
Background
Also featured on Dr. Oz segment Flavoring agent
Uses
Alopecia Weight loss, obesity Increasing lean body mass
Major Drug Interactions

Mostly theoretical drug interactions with caffeine
Examples: antihypertensive agents, cimetidine, stimulants
Mechanism
May increase lipid metabolism and reduce obesity by increasing norepinephrine-induced lipolysis and thermogenesis May increase skin insulin-like growth factor-1
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Raspberry Ketones
Very little research has been done Preliminary studies show raspberry ketones may have some benefits hair growth in patients with alopecia May promote weight loss and help with obesity Raspberries (not the ketone component) being evaluated for anti-cancer properties
Raspberry Ketones
Major Adverse Effects
Concern that it may have stimulant effects like synephrine Theoretically similar structure to capsaicin No reliable information for human use
Major Drug Interactions

Warfarin Potential interactions with antineoplastic agents
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Butterbur
Background
Perennial shrub whose leaves have been used for over 2,000 years
Butterbur
2012 American Academy of Neurology guidelines for episodic migraine prevention1
Review of studies from June 1999-May 2009 to assess efficacy of NSAIDs and CAM for migraine prevention Of the 284 studies reviewed, 15 studies were were Class I or Class II Butterbur was the only nonprescription option that was given Level A classification (established efficacy) Level B (probably effective) Fenoprofen, ibuprofen, ketoprofen, naproxen Magnesium, feverfew, riboflavin
1. Holland S et al. Neurology 2012; 78:1346-1353.
Uses
Prevention of allergic rhinitis Migraine prophylaxis Asthma
Mechanism of action
Thought to decrease concentration of antihistamines and leukotrienes in blood May have antispasmodic and anti-inflammatory effects
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Butterbur
Summary of clinical studies
Butterbur appears to reduce migraine frequency May reduce intensity and duration of migraine May decrease nasal symptoms of allergic rhinitis Doesnt appear to be beneficial for asthma
Butterbur
Major Adverse Effects:
Use products that are pyrrolizidine alkaloid free to avoid risk of hepatotoxic, carcinogenic effects Generally well tolerated Avoid in patients with allergy to ragweed
Dosing
Appears to be beneficial at 75mg twice daily (Petadolax) for migraine Appears to be beneficial at 50mg twice daily (Petaforce) or 8mg three-four times daily (Tesalin)
Major Drug Interactions:

Substrate of CYP450 3A4 Consider avoiding in combination with anticholinergic medications
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Probiotics
Live organisms that when ingested, confer a
therapeutic or preventative health benefit Organisms:
bulgaricus, L. reuteri, L. casei)
Probiotics
Thought to help reestablish gut flora and prevent the
presence of harmful bacteria
Bacteria Lactobacillis species (L. acidophilus, L. rhamnosus, L.

longum, B. lactus)
May also stimulate immune system In children may affect development of immune tolerance Likely/Possibly Effective for:
Treatment of rotavirus Treatment and prevention of antibiotic associated diarrhea (including C. difficile) Treatment of acute diarrhea Reduction in severity of symptoms with irritable bowel syndrome Reduction of atopic dermatitis in at-risk infants Prevention of travelers diarrhea Treatment of pouchitis Treatment of respiratory infections
Bifidobacterium species (B. infantis, B. breve, B.
Yeast Saccharomyces boulardii Benefits of probiotics are strain specific Only a few of probiotic products on the market contain strains that have been studied in clinical trials
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Probiotics Dosing and Administration

Available as capsules, powders, and in food
products such as yogurt Doses vary depending on specific microorganism Dose for bacteria products measured as Colony Forming Units (CFUs) Doses range 1-100 billion CFUs Dose for yeast products measured as milligrams S. boulardii dose ranges from 250-500mg per day
Probiotics General Adverse Effects and Interactions

Generally considered safe and well-tolerated May cause:
Flatulence Mild abdominal discomfort Intestinal gas
Interactions:
Separate antibiotics by 2 hours with bacteria-based probiotics Avoid yeast-based probiotics with antifungals
Precautions:
Cases of pathologic infections
Avoid in immunocompromised patients Avoid in patients at high risk for sepsis
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Acute Infectious Diarrhea

Focus has been on treatment of diarrhea by
decreasing duration or decreasing complications
Summary of clinical studies:
OVERVIEW OF PROBIOTICS INDICATIONS AND EFFICACY
S. boulardii (Florastor), Lactobacillus GG (Culturelle), L. reuteri and some mixtures are most beneficial Cochrane review showed probiotics:
Reduced risk of diarrhea at 3 days Decreased duration of illness by 24-30 hours Were effective as adjunct therapy to rehydration
Only modest effects in diarrhea related to children attending day care centers and nosocomial reasons
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Antibiotic-Associated Diarrhea
Have been assessed for both prevention and
treatment of antibiotic-associated diarrhea (AAD) One meta-analysis showed probiotics reduced risk of developing AAD by 52%
Most effective if started within 72 hours of antibiotic treatment L. rhamnosus GG (Culturelle), L. acidophilus and S. boulardii (Florastor)
Irritable Bowel Syndrome

Probiotics used due to their effects on immune
system and possibility of alteration to gut flora
Variety of strains and dosages tested
Mixed results for this indication B. infantis (Align) appears to be most effective in
reducing symptoms of IBS
Abdominal pain, bloating, and difficult defecation
B. animalis (Activia) may be effective at improving

quality of life and symptoms such as bloating Combination product (VSL#3) may reduce bloating in IBS
Meta-analysis showed significant benefit vs.

placebo for treatment and prevention of AAD
L. rhamnosus GG and S. boulardii (Florastor) Also showed prevention of C. difficile
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Align
Contains bifidobacterium infantis 35624 as
Bifantis with 1 billion CFUs Used to promote healthy bowel function Studies show that it appears to be helpful in relieving symptoms of IBS For children can sprinkle contents into cold drink or food Avoid in patients who are allergic to soy or milk
VSL #3
Specific lactobacillus combination probiotic containing viable
lyophilized bacteria species including:
Lyophilized Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, Streptococcus thermophilus Contains 450 billion CFUs
Used as adjunct treatment in ulcerative colitis, IBS, and

management of an ileal pouch
Used to help reduce abdominal pain and bloating Manufacturer recommends that it be used under supervision
of physician
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VSL #3
Dosing varies per condition being treated
Age and weight based dosing available for children 3 months and older
Culturelle
Contains Lactobacillus GG 10 billion bacteria per
capsule health
Needs to be refrigerated Patients should mix powder with either 4 ounces
Marketed to improve digestion and overall immune

Likely effective for rotavirus diarrhea and other acute diarrhea in infants May be effective for prevention of antibiotic associated diarrhea May be effective for atopic dermatitis
water, yogurt, ice cream, applesauce or other cold food Manufacturer information states safe for children
Dosing varies per condition

For infants and children less than 25 pounds: one capsule daily
Adverse effects: case report of sepsis in infant

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Florastor and Florastor Kids

Contains Saccharomyces boulardii 250 mg (5
billion bacteria) per capsule or packet Marketed to promote, strengthen and maintain intestinal health May be effective for: Prevention of: Antibiotic-associated diarrhea Traveler's diarrhea Diarrhea in tube-fed patients Recurrence of C.difficile Treatment of: HIV-associated diarrhea Diarrhea in infants
Florastor and Florastor Kids

Dosing: 250-500mg 2-4 times per day
Capsules can be opened and contents mixed with food or juice
Adverse effects:
May cause flatulence Case reports of fungemia in immunocompromised patients
Labeling indicates use for patients > 2 months old Avoid with antifungal agents
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Patient Case #2
One of your regular patients comes in to the pharmacy and wants to speak with you. He has to fly out tomorrow morning for a business meeting and cant be sick. He tells you that he only wants to take something natural for his symptoms since those products are safer. You learn the following:
Which of the following probiotics would be the best option?
He is having diarrhea 3 loose stools today and wants to

take some to stop it
He tells you that he has not experienced any weight loss Upon assessment, he does not appear to have any signs of
dehydration or any other signs or symptoms
1. VSL #3 2. Align 3. Culturelle 4. Activia
You see on his profile that he filled a prescription for
amoxicillin 500mg three times per day a few days ago.
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Additional References
Natural Medicines Comprehensive Database. Available at
URL:www.naturaldatabase.com (accessed 2/4/13)
Weston S, Halbert A, Richmond P, Prescott SL. Effects of probiotics on atopic
dermatitis: a randomised controlled trial. Arch Dis Child 2005; 90 (9):892-897.
McKenney JM, Sica D. Prescription omega-3 fatty acids for the treatment of
hypertriglyceridemia. AJHP 2007; 64:595-605.
Savino F, Pelle E, Palumeri E, Oggero R, Miniero R. Lactobacillus reuteri

(American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: A prospective randomized study. Pediatrics 2007; 119;e124-e130 Quigley EMM. The efficacy of probiotics in IBS. J Clin Gastroenterol 2008; 42: S85-S90. Guandalini S. Probiotics for children with diarrhea an update. J Clin Gastroenterol 2008; 42: S53-57. Floch MH, Walker WA, Guandalini S, Hibberd P, Gorbach S, Surawicz C et al. Recommendations for probiotic use 2008. J Clin Gastroenterol 2008; 42: S104-S108. Fedorak RN, Dieleman LA. Probiotics in the treatment of human inflammatory bowel diseases update 2008. J Clin Gastroenterol 2008; 42: S97-S103.
Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oils, omega-3 fatty
acids and cardiovascular disease. Circulation 2002; 106;2747-2757.
Dr. Oz and Green Coffee Project. Available at
URL:http://www.doctoroz.com/videos/green-coffee-bean-project Thomas D, Greer F, Committee on Nutrition. Probiotics and prebiotics in pediatrics. Pediatrics 2010; 126:1271-1231. Guandalini S. Probiotics for the prevention and treatment of diarrhea. J Clin Gastroenterol. 2011; 45(3):S149-S153. Floch MH, Walker WA, Madsen K, Sanders ME, Macfarlane GT, Flint HJ. Recommendations for probiotic use 2011 update. J. Clin Gastroenterol. 2011; 45(3):S168-171. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhea. Cochrane Library. 2010. Available at URL: http://summaries.cochrane.org/CD003048/probiotics-for-treating-acute-infectiousdiarrhoea
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Hume AL. Lactobacillus and antibiotic-associated diarrhea. Pharmacy Today
September 2007.
Thielman NM, Guerrant RL. Acute infectious diarrhea. NEJM 2004; 350-38-47. Probiotics. Pharmacists Letter/Prescribers Letter 2006;22:220704. Canani RB, Cirillo P, Terrin G, Cesarano L, Spagnuolo MI, Vincenzo A et al.
Probiotics for treatment of acute diarrhoea in children: randomised trial of five different preparations. BMJ 2007; 335-340
Kligler B, Cohrssen A. Probiotics. Am Fam Physician. 2008; 78:1073-1078. Vanderfoof JA, Young R. Probiotics in the United States. Clinical Infectious
Diseases 2008; 45:S67-72. NCCAM. Get the facts: An introduction to probiotics. 2008. Available at URL:http://nccam.nih.gov/health/probiotics/ Sazawal S. Hiremath G, Dhingra M, Malik P, Deb S, Black RE. Efficacy of probiotics in prevention of acute diarrhea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infec Dis 2006; 6(6):374-382. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006; 149(3):367-372.
VITAMINS AND MINERALS
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Some Thoughts on Vitamins and Supplements

If you heaped all of the vitamins you need each
day in a pile, that pile would be smaller than the period at the end of this sentence. Dr. David Reuben The problem is not the lack of vitamins, but the overconsumption of refined foods that inhibit their manufacture and use or destroys them once consumed
Some thoughts on Food as Medicine

The difference in what is called a food and what is
called a medicine is that foods have milder qualities
When most foods are used therapeutically,

concentrated quantities must be taken to achieve results Herbs have stronger qualities and flavors and must be used in prescribed doses to effect a positive change
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Does Everyone Need to take Vitamins and Supplements?

Ask why the patient is considering a vitamin or
supplement
Any problems with getting all vitamins and nutrients from foods?
Dirty Dozen foods

apples celery sweet bell peppers peaches strawberries imported nectarines grapes spinach lettuce cucumbers domestic blueberries potatoes green beans kale, collards, and leafy greens
Clean 15 foods

onions sweet corn pineapples avocado cabbage sweet peas asparagus mangoes eggplant kiwi domestic cantaloupe sweet potatoes grapefruit watermelon mushrooms
Evaluate the diet (vegetarian?) Evaluate situations and medical conditions that
may lead to depletion of vitamins and minerals (gastric bypass?) Evaluate current OTC and prescription medications that may lead to interactions or depletions
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Vitamins, Minerals, Supplements

The Womens Health Initiative
Study showed there was not any reduction in cardiovascular disease or cancer risk in postmenopausal women that took a MVI (multivitamin) daily Many products contain excessive amounts of individual vitamins or are adultered to give the natural product therapeutic benefits Some products are contaminated with lead, arsenic, mercury and other toxins through the planting, harvesting, processing steps
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Multivitamins in the News - Data from the Iowa Women's Health Study
Multivitamins, folic acid, iron, and copper,

may be associated with increased total mortality risk in older women They also found that, in contrast to the findings of many previous studies, calcium was associated with decreased risk
Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr. Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Arch Intern Med. 73 2011;171:1625-1633.
Multivitamins and Supplements

When the Iowa Women's Health Study started in the
1980s, there was a good theory that antioxidants and supplements could be beneficial because they provide additional nutrients. Most studies have found that there is really no beneficial effects on risk for cardiovascular disease or cancer, and some found that some of the supplements could be harmful. * In the Physicians Health Study II of 14,461 male physicians in the US, the use of multivitamins over 10 years did not reduce cardiovascular events, stroke, myocardial infarction or cardiovascular mortality, but did modestly reduce the risk of total cancer.
* JAMA. 2012;308(17):1802-1803. * JAMA. 2012;308(18):1916-1917.
Vitamins
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Vitamin Deficiencies
Can and do occur 1. Due to substance abuse, poverty, eating disorders, dementia 2. Loss of teeth, difficulty in swallowing 3. Decreased sense of taste and smell 4. Decreased absorption (gastric by-pass), irritable bowel syndrome 5. Metabolic requirements of chronic diseases, injury, infection 6. Others Nutritional Supplements Should be just that instead of as a replacement
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Vitamins
Nutrients that cannot be made in the body in
sufficient quantities and must be consumed
DRI Dietary Reference Intake

EAR estimated average requirement average daily intake to meet the requirements of 50% of healthy individuals RDA recommended dietary allowance average daily intake to meet nutrition requirements for 9798% of healthy individuals AI - adequate intake used to determine adequate nutritional amounts when RDA not available UL upper intake levels maximum daily intake that should not cause adverse effects
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Vitamins
The percent DV (%DV indicates the percentage of the DV provided in one serving
Fat Soluble Vitamins
SolubleSoluble Vitamins Fat Soluble verses Water Water C, B Not stored in the body and excessive amounts are usually eliminated in the urine
A,D,E,K Soluble in lipids
A food providing 5% of the DV or less per serving is

a low source while a food that provides 10-19% of the DV is a good source A food that provides 20% or more of the DV is high in that nutrient
Absorbed into the lymphatic system of the small intestine. Absorption facilitated by bile Normal and excessive amounts are stored In body tissues Celiac disease, cystic fibrosis, cirrhosis of the liver and short gut syndrome can lead to deficiencies due to malabsorption Cholestyramine, orlistat and mineral oil may also lead to deficiencies in Vitamins A,D,E,K
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International units (IU) are used to describe doses of fat soluble vitamins
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Vitamin A
Fat soluble vitamin
Includes the retinoids and carotenoids
Vitamin A
Found in two forms:
1. 2. Preformed Vitamin A (retinol and retinyl ester) from animal sources - liver, egg yolk, Provitamin A (beta carotene) from plant sources - dark green vegetables, red, orange and deep yellow fruits and vegetables
Essential for normal growth, normal skeletal muscle

formation, tooth development
Needed for proper functioning of the organs,

especially the eye
Helps regulate the immune system May help lymphocytes fight infections more
effectively
In healthy adults, 90% of bodys Vitamin A is stored

in the liver as retinyl esters
Converted to retinol in the small intestine
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http://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/ Accessed 12/05/2012
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Ways to Measure for Deficiencies

Minimal risk of deficiency in adults Infants and very young children may be deficient
because not old enough to have stored enough Plasma levels Plasma retinol concentration lower than 0.70 micromoles/L or 20 micrograms/dL indicates Vitamin A deficiency
Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001
Food Sources of Vitamin A

Food Sweet potato Beef liver (3 ounces) Spinach (1/2 cup boiled) Carrots (raw) cup Cantaloupe (1/2 cup) Peppers, sweet, red (1/2 cup) Mangos (1 whole) Black-eyed peas (1 cup) Broccoli (1/2 cup) mcg RAE per serving 1403 6582 573 459 488 135 112 66 60 IU per serving 28,058 22,175 11,458 9,189 3,743 2,706 2,240 1,305 1,208
.
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Recommended Daily Allowance

RDAs for vitamin A are given as mcg of retinol activity
equivalents (RAE) to account for the different bioactivities of animal, plant and supplemental sources of Vitamin A We convert all dietary sources of vitamin A into retinol Given in mcg of retinol activity equivalents (RAE)
1 mcg of retinol = 12 mcg of beta-carotene 1 mcg of retinol = 24 mcg of alpha-carotene
Source Determines Amounts

An RAE cannot be
directly converted into an IU without knowing the source(s) of vitamin A A mixed diet containing 900 mcg RAE provides between 3,000 and 36,000 IU of vitamin A, depending on the foods and supplements consumed
RDA 900 mcg 3000 IU RAE 6000 IU Source Preformed Vit A If betacarotene from supplements
If taking Vitamin A supplements, reported as IU

1 IU retinol = 0.3 mcg RAE 1 IU beta-carotene from supplements = 0.15 mcg 1 IU betacarotene from food = 0.05 mcg 1 IU alpha-carotene = 0.025 mcg
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18,000 IU If betacarotene from food 36,000 IU If alphacarotene from food
85
Recommended Dietary Allowances (RDA) and Tolerable Upper Levels (UL)

RDA male RDA female Tolerable Upper Levels (UL) for preformed Vit A male and female 600 mcg RAE (2000 IU) 600 mcg RAE (2000 IU) 900 mcg RAE (3000 IU) 1700 mcg RAE (9333 IU) 3000 mcg RAE (10,000 IU)
Causes of Vitamin A Deficiency

Children and pregnant women at greatest risk of
deficiency
Other conditions that reduce Vitamin A absorption

Fat malabsorption Cancer TB Pneumonia, nephritis, UTI Prostate disease
0-6 months 7-12 months 1-3 years 4-8 years 9-13 years 19-51 + years
400 mcg RAE 500 mcg RAE 300 mcg RAE 600 mcg RAE 900 mcg RAE 900 mcg RAE
400 mcg RAE 500 mcg RAE 400 mcg RAE 600 mcg RAE 700 mcg RAE 700 mcg RAE
Neomycin, cholestyramine and orlistat may reduce

Vitamin A absorption
RAE = retinol activity equivalents
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Symptoms of Vitamin A Deficiency

Night blindness Loss of appetite Impaired taste and smell Impaired balance Xeropthalmia - Abnormal dryness and thickening of the conjunctiva and cornea Bitots spot triangular shaped spots on the cornea
Vitamin A Toxicity and SE

Recommended daily intake:
Adult men - 900 mcg/day (3000IU) Adult women - 700 mcg/day (2330IU)
Adult Tolerable Upper Intake Limit = 3000 mcg/day Toxicity risk is from consuming large amounts from
animal sources or from supplements
Excessive amounts of Vit A have been shown to

increase the risk of bone fractures (animal source preformed) Increased risk of birth defects, liver abnormalities, reduced bone mineral density that may result in osteoporosis and central nervous system disorders
88 89
http://www.eyeway.org/inform/vitmin.htm
Vitamin A Toxicity and SE

Toxic symptoms can arise after consuming very large
amounts of vitamin A over a short period of time. (Consuming 25,000 IU/kg at one time or 4000 IU/kg daily chronically can cause toxicity in adults)
Clinical Trials with Vitamin A Supplements

ATBC Study (Alpha-Tocopherol, Beta-Carotene
Cancer Prevention Study) and CARET Study (Carotene and Retinol Efficacy Trial) showed that large doses of beta carotene with or without 25,000 IU of retinyl palmitate did not prevent lung cancer AREDS2 (Age Related Eye Disease Study) follow up study to see if beta carotene combined with other antioxidants and minerals can decrease macular degeneration Measles in several studies, giving large doses of vitamin A (200,000 IU) on 2 consecutive days reduced mortality from measles
Yang HM, Mao M, Wan C. Vitamin A for treating measles in children. Cochrane Database Syst Rev 2011;2005. 91
Signs of acute toxicity include: N/V Headache Dizziness Blurred vision and lack of muscular coordination - Painful joints have been well-documented.
The teratogenic effects of -cis-retinoic acid (Accutane)
90
B Vitamins
Water soluble B-complex vitamin Vitamin B2 (Riboflavin) - Use may cause
Niacin (Nicotinic Acid) Toxicity and SE

Niacin can cause flushing of the skin, headache, N/V.
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discoloration and a yellow-orange colored urine Niacinamide does NOT lower TG and LDL levels
Itching of the skin with symptoms improving over several weeks Extended release version MAY cause less flushing, but may cause more GI side effects and possible harm to the liver. Avoid in people with GI disorders Niacin can cause histamine to be released, so monitor in patients with asthma and allergies May raise BS levels and lead to hyperuricemia LFTs should be performed at the same frequency as statins when used at doses to improve cholesterol levels AIM-HIGH
93
Flushing verses Non-flushing

Three forms of niacin 1. Nicotinic acid 2. Nicotinamide 3. Inositol hexaniacinate
Vitamin C (ascorbic acid)

GENERAL Water soluble vitamin Required for making collagen in bones, cartilage, muscle, and blood vessels. Required for making L-carnitine, and certain neurotransmitters Antioxidant Helps the body absorb iron from plant sources
Flush free niacin is also known as inositol

hexaniacinate
May not have SE of flushing, but may not lower LDL

or raise HDL cholesterol
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Vitamin C
Only 10% to 20% of adults get the recommended
nine servings of fruits and vegetables daily. RDI for adult males = 90 mg/day and for adult females = 75 mg/day Adult Tolerable Upper Intake Limit = 2000 mg/day Food sources = green and red peppers, broccoli, spinach, tomatoes, potatoes, citrus fruit, strawberries
Vitamin C and Colds

Evidence to date suggests that regular intakes of
vitamin C at doses of at least 200 mg/day do not reduce the incidence of the common cold in the general population, but such intakes might be helpful in people exposed to extreme physical exercise or cold environments and those with marginal vitamin C status, such as the elderly and chronic smokers. The use of vitamin C supplements might shorten the duration of the common cold and lessen symptom severity in the general population, possibly due to the anti-histamine effect of highdose vitamin C .
96 97
Vitamin C Deficiency
Acute vitamin C deficiency leads to scurvy. Signs can appear
within 1 month of little or no vitamin C intake (below 10 mg/day) Initial symptoms can include fatigue, malaise, and inflammation of the gums As vitamin C deficiency progresses, collagen synthesis becomes impaired and connective tissues become weakened, causing petechiae, ecchymoses, purpura, joint pain, poor wound healing, hyperkeratosis, and corkscrew hairs Additional signs of scurvy include depression as well as swollen, bleeding gums and loosening or loss of teeth due to tissue and capillary fragility Iron deficiency anemia can also occur due to increased bleeding and decreased non-heme iron absorption secondary to low vitamin C intake Left untreated, scurvy is fatal
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Vitamin C Toxicity
No real downside to taking a 500-milligram supplement,
except that some types may irritate the stomach (2000 mg/d) and possibly cause diarrhea (can take a nonacidic, buffered form of the vitamin. Approximately 70%90% of vitamin C is absorbed at moderate intakes of 30180 mg/day. At doses above 1 g/day, absorption falls to less than 50% and absorbed, un-metabolized ascorbic acid is excreted in the urine .. EXCESSIVE AMOUNTS MAY LEAD TO KIDNEY STONES Repeated daily doses of 2000 mg or more will acidify the urine
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Vitamin C
INTERACTIONS May increase the amount of aspirin and NSAIDs in the blood if taken with Vit C Others
Vitamin D
According to a 2009 report in the "Archives of Internal Medicine," as much as 77 percent of the American population is vitamin D deficient Cholecalciferol (vitamin D3) naturally occurring form of Vit D Synthesized in the skin after exposure to sunlight Ergocalciferol (vitamin D2) used as a food additive
Acts as both a hormone and a vitamin Renal and hepatic dysfunction may lead to Vitamin D
deficiency because of their role in vitamin D metabolism and elimination

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100
Vitamin D
Vitamin D Promotes calcium absorption in the gut Maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone Vitamin D is needed for the proper formation of bone and mineral homeostasis Involved with parathyroid hormone, phosphate and calcitonin in the homeostasis of serum calcium May reduce the risk of heart disease and some cancers
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Vitamin D2 versus Vitamin D3

Vitamin D2 Vitamin D2 comes from plants Vitamin D3 When UVB light from the sun strikes the skin, we synthesize vitamin D3 Vitamin D3 may be less toxic than D2 Vitamin D3 is the more potent form of vitamin D
Vitamin D2 does not bind as well to the receptors in the human tissues compared to vitamin D3
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Vitamin D2 versus Vitamin D3

Vitamin D3 is more stable on the shelf compared to
D2, and is more likely to remain active for a longer period of time and when exposed to different conditions (temperature, humidity, and storage). Vitamin D3 has been the most utilized form of vitamin D in clinical trials, and there have only been a few clinical trials of vitamin D2 to prevent bone fractures in adults. Vitamin D3 is more effective at raising and maintaining the vitamin D blood test ( D2 binds less tightly to the vitamin D receptors in the body; therefore, D2 does not circulate as long in the body, which means it has a shorter half-life).
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Vitamin D Deficiency
From inadequate intake, GI disorders, chronic renal
failure
Inadequate sunlight exposure or overuse of sunscreen American Academy of Pediatrics breastfed infants
need 400 IU vit D supplement/day. Once weaned or non-breast fed infants need 400 IU/day People with dark skin Patients that have a BMI > 30 or have had gastric bypass surgery Long term phenytoin therapy - Anti-seizure or anticonvulsant medications, such as phenobarbital, Dilantin, Mysoline, and Depakote - lower levels of vitamin D caused by the liver removing an increased amount of vitamin D from the body
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Serum concentration of 25(OH)D is the best
indicator of vitamin D status. Reflects vitamin D produced from sun exposure and that obtained from food and supplements and has a fairly long circulating half-life of 15 days. In the kidney, 25 hydroxy vitamin D is converted into the active form of vitamin D Serum 25(OH)D levels do not indicate the amount of vitamin D stored in body tissues Screening for Vitamin D deficiency NOT recommended for everyone
Circulating 1,25(OH)2D is generally not a good
indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe When the dose of vitamin D is <1,000 IU/day, there is a steeper rise in serum 25(OH)D A lower, more flattened response is seen when the dose is 1,000 IU/day at higher daily doses.
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Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health

nmol/L ng/ml Associated with vitamin D deficiency. <12 May lead to rickets in infants and children and osteomalacia in adults 1220 Considered inadequate for bone and overall health in healthy individuals
Toxicity and SE of Vitamin D

Recommended daily intakes are 600 IU/day for most
adult men and women and 800 IU/day for men and women > 70 years old The upper limit for Vit D is 4000 IU daily If adults are deficient, they can take 50,000 IU once a week or 6,000 IU daily for 8 weeks until levels are > 30 ng/ml Excessive amounts of Vit D can lead to anorexia, hypercalcemia, kidney stones, renal failure and increase the risk of some cancers Excessive amounts may increase the risk of breast, esophageal, prostate and pancreatic cancer, vascular and tissue calcification
<30
3050
50 >125
Considered adequate for bone and overall 20 health in healthy individuals >50 potential adverse effects can occur, particularly >150 nmol/L (>60 ng/mL)
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The Finnish Vitamin D Trial (FIND)

A large-scale trial, the Finnish Vitamin D Trial
(FIND) will be done to determine whether vitamin D supplementation helps in the primary prevention of cardiovascular and cancer Studies like the VITamin D and omegA-3 triaL (VITAL) trial in the United States are under way to investigate whether vitamin D supplementation reduces the risk for cardiovascular disease or cancer.
Vitamin E (Tocopherol)
Fat soluble vitamin Functions as an anti-oxidant, especially when combined
with selenium and Vitamin C
Many clinical trials with Vit E have not shown clinical
benefits in treating chronic conditions such as Parkinsons and Alzheimer's The HOPE and HOPE-TOO trials provide evidence that moderately high doses of vitamin E supplements do not reduce the risk of serious cardiovascular events among men and women >50 years of age with established heart disease or diabetes Naturally occurring vitamin E exists in eight chemical forms that have varying levels of biological activity
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111
Serum concentrations of vitamin E (alphatocopherol) depend on the liver, which takes up the nutrient after the various forms are absorbed from the small intestine. The liver preferentially re-secretes only alphatocopherol via the hepatic alpha-tocopherol transfer protein. The liver metabolizes and excretes the other vitamin E forms . Blood and cellular concentrations of other forms of vitamin E are lower than those of alpha-tocopherol
Found in wheat germ, vegetable oils, margarine,
nuts, green leafy vegetables
Low-fat diets might provide insufficient amounts of

Vitamin E, unless people increase their intakes of nuts, seeds, fruits, and vegetables Average diet contains 3-15 mg of Vit E Deficiency is rare premature, very low birth weight infants and patients with absorption disorders (cystic fibrosis and biliary disease) Deficiency associated with symptoms of peripheral neuropathy and muscle weakness
113
112
Supplements of vitamin E typically provide only alpha
tocopherol, although "mixed" products containing other tocopherols and even tocotrienols are available. A given amount of synthetic alpha-tocopherol (listed on labels as "DL" or "dl") is only half as active as the same amount (by weight in mg) of the natural form (labeled as "D" or "d"). People need approximately 50% more IU of synthetic alpha tocopherol from dietary supplements and fortified foods to obtain the same amount of the nutrient as from the natural form. Most vitamin-E-only supplements provide 100 IU of the nutrient, which is higher than the 22IU RDA Daily doses for health benefits are between 400 and 1000 IU/day. 1 mg of alpha-tocopherol vitamin E is = to 1.49 IU
114
Vitamin E Toxicity and SE

May increase risk of HF, hemorrhagic stroke, and
fetal loss if given to a women with preeclampsia
Recommended intake is 15 mg/day (22 IU) for most

adult men and women
Adult tolerable upper limits 1000 mg/day (1490 IU) MAY enhance warfarin action if taken in excessive
amounts
115
Vitamin E (Drug Interactions)

Plasma levels of vitamin E may be lowered by
anticonvulsants (phenobarbital, phenytoin and carbamazepine). Vitamin E may decrease the absorption of desimpramine, chlorpromazine, propranolol Vitamin E in large doses (> 1000 mg) may enhance the effect of anticoagulants (warfarin, heparin, dalteparin, tinzaparin, enoxaparin). High doses of vitamin E may enhance the effects of antiplatelet drugs (aspirin, dipyridamole, eptifibatide, clopidogrel, and abciximab). Orlistat (Xenical) has been shown to reduce the absorption of certain fat soluble vitamins such as vitamin E.
116
Minerals
There are more deficiencies in minerals than
vitamins
Minerals needed for assimilation of food, proper

metabolism, and offsetting the deterioration of bones, muscles and other solid structures of the body The most assimilated form of minerals comes from plants
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Mineral Composition in the Body

Mineral Calcium Phosphorus Potassium Sulfur Chlorine Sodium Magnesium Iron Trace minerals iodine, manganese, copper, nickel, arsenic, bromine, silicon, selenium Percentage in the body 39% 22% 5% 4% 3% 2% 0.7% 0.15% Trace amounts
Sources of Minerals from Foods

Mineral Calcium Iron Magnesium Phosphorus Potassium Selenium Sodium Zinc Food sources Milk, seaweed, almonds and greens (avoid spinach and chard) Kelp, sesame seeds, greens Kelp, almonds, legumes, dried fruit, banana, potato Seeds, nuts, legumes, grains, dried fruit Dried fruit, nuts, avocado, carrots, bananas Brazil nuts, whole grains, shellfish Kelp, celery, raisins, dried fruit Meat, wheat germ
Trace minerals iodine, Trace amounts manganese, copper, nickel, arsenic, bromine, silicon, selenium 118 119
Different Calcium Salts

Calcium Salt % Elemental Calcium
Calcium
RDI for adult males and females = 1000 1200
mg/day
Calcium gluconate
9.3
Adult Tolerable Upper Intake Limit = 2000 2500

mg/day
Food sources of calcium = milk, yogurt, cheese,

Calcium citrate 21
clams, oysters, greens
Calcium carbonate
40
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Calcium and Spinach

Calcium content of spinach is 115 mg per half cup
cooked Spinach and chard may bind to calcium making it harder to absorb Because of the interference of oxalic acid, you would have to eat more than 16 cups of raw or more than eight cups of cooked spinach to get the amount of calcium available in one cup of yogurt.
Calcium
USES dietary supplementneeded for vascular contraction, vasodilation, muscle function, nerve transmission SE/ADR /CAUTIONS CONSTIPATION use with caution in patients with hypophosphatemia, hypercalcemia DRUG INTERACTIONS increased urinary calcium excretion when used in combination with aluminum antacidsmay decrease peak plasma levels and bioavailability of atenolol.. MEDICATION Atenolol PROBLEM Decreased bioavailability and peak plasma levels Decreased GI absorption May reduce bioavailability of Hypercalcemia may occur when used together
Iron Quinalone antibiotics Thiazide diuretics
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Calcium
Take calcium carbonate products WITH FOOD to
increase absorption
Iron
Type of iron Percent elemental iron 33% 20% 12% Mg dose Elemental iron content in mg 106 mg 65 mg 36 mg
Can take calcium citrate without food, but have to

take twice as much citrate as carbonate form
Iron fumarate Iron sulfate Iron gluconate
325 mg 325 mg 325 mg
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Iron
RDI for adult females 19-50 YO = 18 mg/day, for
females > 50 YO, 8 mg/day RDI for adult males 8 mg/day Adult Tolerable Upper Intake Limit = 45 mg/day Full term infants are born with enough iron for 6 months, 11 mg/day RDI from 6-12 months Food sources of iron: Heme form = liver, meat, seafood Non-heme form = dark green vegetables, iron fortified foods, beans
Iron Toxicity
Iron overdose is one of the leading causes of death in
children under age 6 iron/tablet
Prenatal vitamins may have 60-100 mg of elemental Chewable MVI -15-18 mg elemental iron/tablet
Signs of GI toxicity seen after 20 mg/kg ingested
Moderate toxicity when elemental iron consumed
exceeds 40 mg/kg Consuming more than 60 mg/kg can head to death More than 4 episodes of vomiting (especially with blood) may indicate toxic iron consumption Classified in 5 stages with the 1st stage occurring within 6 hours after ingestion
hsc.unm.edu/pharmacy/poison/docs/pdf/Vitamins%20&520Iron.pdf
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127
Magnesium
Needed for normal bone growth and the proper
function of enzymes, maintenance of muscle and nerve functions and normal heart rhythm and improves immune system Cannot correct hypocalcemia or hypokalemia without magnesium RDI for males (31 to > 70 YO) = 420 mg/day RDI for females (31 to > 70 YO) = 320 mg/day Adult Tolerable Upper Intake Limit = 350 mg/day Food sources of magnesium = whole grain cereals, tofu, nuts, legumes, green vegetablesprocessing food removes almost all of the magnesium
128
Magnesium
USES dietary supplement, constipation, soak for muscle aches Unofficial uses to prevent kidney stones, inhibit contractions in tocolysis (preterm labor), leg cramps, improved pulmonary function, lower BP and BS Deficiency (causes) - malabsorption, diarrhea, alcoholism, diuretic use Deficiency (symptoms) CNS stimulation, delirium, convulsions, irritability, loss of appetite, N/V, fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions and cramps (hyperglycemia in people with diabetes) CAUTIONS use with caution in patients with renal insufficiency Signs of excess magnesium - changes in mental status, nausea, diarrhea, appetite loss, muscle weakness, extremely low blood pressure, and irregular heartbeat [ DRUG INTERACTIONS decrease absorption of digoxin
129
Different Magnesium Salts

Magnesium Salt % MAGNESIUM Bioavailability high high Use Dietary supplement laxative Magnesium 12 chloride (hydrous) Magnesium citrate (anhydrous) Magnesium gluconate (hydrous) Magnesium hydroxide (anhydrous) Magnesium oxide (anhydrous) Magnesium sulfate (hydrous) 16.2
Zinc
Responsible for over 100 enzyme reactions Necessary for growth and development Avoid taking this medication together with foods that are Used for boosting the immune system, treating the
high in calcium or phosphorus, which can make it harder for your body to absorb zinc sulfate
5.4
41.7
60.3 9.9
low
supplement Soak for muscle aches and laxative
common cold and recurrent ear infections, and preventing lower respiratory infections. Using zinc as a pill or a nose spray doesnt prevent colds. May shorten the duration of colds by 3-4 days if taken within 24 hours of onset of cold. Zinc lozenges used to treat colds usually contains zinc gluconate or zinc acetate (3.3 mg of elemental zinc in each lozenge). One lozenge every 2-4 hours for up to lozenges per day used to treat colds
131
130
Zinc
Used to treat malaria and other diseases caused by
parasites RDI for adult males = 11 mg/day and for adult females = 8 mg/day Adult Tolerable Upper Intake Limit = 40 mg/day Food sources of zinc = Shellfish, oysters, liver, beef, milk, wheat germ
Zinc TOXICITY AND SE

Zinc is LIKELY SAFE for most adults when taken by mouth in
amounts not larger than 40 mg per day. In some people, zinc might cause nausea, vomiting, diarrhea, metallic taste, kidney and stomach damage, and other side effects. Using zinc on broken skin may cause burning, stinging, itching, and tingling. Taking high amounts of zinc is LIKELY UNSAFE. High doses above the recommended amounts might cause fever, coughing, stomach pain, fatigue, and many other problems. Taking more than 100 mg of supplemental zinc daily or taking supplemental zinc for 10 or more years doubles the risk of developing prostate cancer. There is also concern that taking large amounts of a multivitamin plus a separate zinc supplement increases the chance of dying from prostate cancer. Taking 450 mg or more of zinc daily can cause problems with blood iron. Single doses of 10-30 grams of zinc can be fatal. 133
132
Zinc -TOXICITY AND SE

Zinc nose sprays (Zicam, Cold-Eeze) are
POSSIBLY UNSAFE. These products may cause loss of ability to smell. In June 2009, the US Food and Drug Administration (FDA) advised consumers not to use certain zinc-containing nose sprays (Zicam) after receiving over 100 reports of loss of smell. The maker of these zinc-containing nose sprays has also received several hundred reports of loss of smell from people who had used the products. Avoid using zinc nose sprays.
Zinc PREGNANCY AND LACTATION

Zinc is LIKELY SAFE for most pregnant and
breast-feeding women when used in the recommended daily amounts (RDA). Pregnant women over 18 should not take more than 40 mg of zinc per day; pregnant women age 14 to 18 should not take more than 34 mg per day. Breast-feeding women over 18 should not take more than 40 mg of zinc per day; breast-feeding women age 14 to 18 should not take more than 34 mg per day.
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135
Zinc Drug/Supplement Interactions

Antibiotics (Quinolone antibiotics) Zinc might decrease how much antibiotic the body absorbs. Taking zinc along with some antibiotics might decrease the effectiveness of some antibiotics. To avoid this interaction, take antibiotics at least 2 hours before or 4-6 hours after zinc supplements. Some of these antibiotics that might interact with zinc include ciprofloxacin (Cipro), levofloxacin (Levaquin) Antibiotics (Tetracycline antibiotics) Zinc can attach to tetracyclines in the stomach. This decreases the amount of tetracyclines that can be absorbed. Taking zinc with tetracyclines might decrease the effectiveness of tetracyclines. To avoid this interaction, take tetracyclines 2 hours before or 4-6 hours after taking zinc supplements. Calcium Calcium supplements might decrease dietary zinc absorption. This usually doesn't seem to be much of a problem. However, this interaction can be avoided by taking calcium supplements at bedtime instead of with meals.
How do we advise patients that ask about dietary supplements?
136
137
Selection of dietary supplements

Ask why the patient is considering a vitamin or
supplement
Drug Nutrient Depletion Resources

Natural Medicines Comprehensive Database
Pharmacist Letter
Evaluate the diet (vegetarian?) Evaluate situations and medical conditions that may
1. 2.
lead to depletion of vitamins and minerals (gastric bypass?) Known contraindications? Evaluate current OTC and prescription medications that may lead to interactions or depletions Time release verses regular release Oral versus injection
Pharmavite Vitamin Wheel RDA/AI, UL lists
Natural Standard Vitamin & Herb University - Pharmavite
138
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Resources

Company specific websites Nutrition Possible.com (Centrum) www.vitaminuniversity.com (Pharmavite) Printed charts List of USP (Dietary Supplement Verification) verified companies http://www.usp.org/uspverification-services/usp-verified-dietarysupplements/verified-supplements
Quality
Use and sell brands that you know have consistent
doses of ingredients across batches
Low in toxins Come from companies that meet GMP
140
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USP Verification Process

Ensures Quality ingredients are used Product is consistent across batches as far as potency and purity (lists any potential allergens) Product label meets specifications and label claims that are valid Ensures Good Manufacturing Processes (GMPs) are met
USP Verification Process

PROCESS Expert committee completes an initial review Manufacturing processes are evaluated Quality control review is completed Product samples are tested in a laboratory USP Verified mark is awarded Periodic product testing is performed
142
143
USP Verified Companies

Banner Pharmacaps Inc.
Selected private-label brand supplements
USP Verified Companies

Perrigo Company of South Carolina
IVC Nutrition Corporation

International Vitamin Corporation

Selected store and private-label brand supplements
Natural Factors Nutritional Products

Joun Health Inc. Pharmavite LLC

Nature Made brand supplements Nature's Resource brand herbal supplements Selected store and private-label brand supplements
NBTY Inc.
Kirkland Signature brand supplements
Robinson Pharma Inc.

Northwest Natural Products Uni-caps, LLC

Schiff Nutrition
Schiff brand supplements Selected store and private-label brand supplements
WePackItAll
144 145
Mega doses of vitamins and supplements

Doses are usually 50 to 150% of the dietary
reference intake amount Avoid a product has more than 200% of the dietary reference intake amount

Vitamin/Supplement/Herb Information Sources

Natural Standard Consumer Lab (requires paid subscription) Office of Dietary Supplements (ods@nih.gov) Nature Made vitamins (www.naturemade.com) Vitamin Herb University (www.vitaminherbuniversity.com) University of Maryland Medical Center website (http://www.umm.edu/altmed/ ) University of Michigan http://www.med.umich.edu/1libr/aha/umherb01.htm American Botanical Council Pharmacist Letter Natural Medicines Database www.RxFiles.ca (herbal-drug interaction chart) NCCAM - National Institutes of Health, National Center for Complementary and Alternative Medicine www.nccam.nih.gov USDA National Agriculture Library Dietary Supplements: Resources for Professionals http://www.nal.usda.gov/fnic/pubs/bibs/gen/dietarysupplementsprofessionals.pdf Memorial Sloan-Kettering Cancer Center About Herbs, Botanicals & Other Products
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147
Which of the following regulations requires manufacturers to report serious adverse effects of herbs and dietary supplements?
A. Dietary Supplement Health and Education Act of 1994 B. Federal Food Drug and Cosmetic Act C. Dietary Supplement and Nonprescription Consumer Protection Act D. Kefauver Harris Amendment
148
A patient with dyslipidemia wants to start omega-3 fatty acids. His profile shows elevated LDL, elevated triglycerides and at goal HDL. Which of the following doses of omega-3 fatty acids would you tell him is most effective for him to reach target lipid goals?
A. 1 gram per day B. 4 grams per day C. More is better so he

should take as much as he can tolerate D. None of the above, omega-3 fatty acids will not be beneficial for this patient
149
What Vitamin is fat soluble, necessary for proper eye function and may increase bone fractures if taken in excess?
What is a reputable resource for finding information about the uses, doses and potential side effects of herbs, vitamins and supplements?
A.Vitamin A B.Vitamin B1 C.Vitamin C D.Vitamin D3
A. National Inquirer B. Natural Standard C. Vitamin Kingdom D. Happy Hempster

Health Highlights
150
151
Key Points
Use of herbal products and dietary supplements is
growing in the US; many patients use as adjunct to traditional care In some cases, it is necessary for patient to supplement with herbs and dietary supplements Evidence based information can be found and should be used Natural does not = safe
152

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Evidence-Based Recommendations for Herbal and Dietary Supplements

Procter and Gamble

Target Audience: Pharmacists ACPE#: 0202-0000-13-017-L04-P Activity Type: Knowledge-based

2013 by the American Pharmacists Association. All rights reserved.

A. 1 gram per day B. 4 grams per day C. More is better so he

A.Vitamin A B.Vitamin B1 C.Vitamin C D.Vitamin D3

Do you currently use herbs and/or dietary supplements?

A. National Inquirer B. Natural Standard C. Vitamin Kingdom D. Happy Hempster

Trends in Consumer Use of Herbs/Dietary Supplements

According to the 2007 CDC survey, use of CAM

2013 by the American Pharmacists Association. All rights reserved.

Popular Herbs and Dietary Supplements: 2007 National Health Survey

Trends in Consumer Use of Herbs/Dietary Supplements

Popular Herbs and Dietary Supplements: 2011 Harvard Survey

REGULATIONS OF HERBS AND DIETARY SUPPLEMENTS

Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311

Regulatory Role of FDA

1962: Kefauver-Harris Amendment 1994: Dietary Supplement Health and Education

2006: Dietary Supplement and Nonprescription

June 22, 2007: New Dietary Supplement Current

2013 by the American Pharmacists Association. All rights reserved.

Dietary Supplement and Nonprescription Drug Consumer Act

Herbs and Dietary Supplements

HERBS AND DIETARY SUPPLEMENTS

Fish Oils (Omega-3 Fatty Acids)

Fish Oils (Omega-3 Fatty Acids)

2013 by the American Pharmacists Association. All rights reserved.

Fish Oils (Omega-3 Fatty Acids)

Fish Oils (Omega-3 Fatty Acids)

Meta-analysis of 20 studies on omega-3 fatty acids

Patient with high triglycerides

Adapted from table 5: Kris-Etherton et al. Circulation 2002; 106;2747-2757.

Fish Oils (Omega-3 Fatty Acids)

Example Fish Oils (Omega-3 Fatty Acids) Label

Fish Oils (Omega-3 Fatty Acids)

Fish Oils (Omega-3 Fatty Acids)

Patient counseling suggestions to minimize adverse

Vascepa (icosapent ethyl)

2013 by the American Pharmacists Association. All rights reserved.

Fish Oils (Omega-3 Fatty Acids)

Fish Oils (Omega-3 Fatty Acids) Summary

Titrate the dose increase slowly FDA approved product is available

1. EcoKrill 2. Iceland Health

3. Neither would help

What would be the recommended dose?

1. 1 gram daily 2. 4 grams daily 3. As much as he

2013 by the American Pharmacists Association. All rights reserved.

Green Coffee Extract

Green Coffee Extract

Green Coffee Extract

Major Drug Interactions

Major Drug Interactions

2013 by the American Pharmacists Association. All rights reserved.

Major Drug Interactions:

Bacteria Lactobacillis species (L. acidophilus, L. rhamnosus, L.

Bifidobacterium species (B. infantis, B. breve, B.

2013 by the American Pharmacists Association. All rights reserved.

Probiotics Dosing and Administration

Probiotics General Adverse Effects and Interactions

Acute Infectious Diarrhea

Summary of clinical studies:

OVERVIEW OF PROBIOTICS INDICATIONS AND EFFICACY

Irritable Bowel Syndrome