Dietary Supplements and Diabetes:What’s New?

Laura Shane-McWhorter, PharmD,BCPS, BC-ADM, CDE, FASCP, FAADE

University of Utah College of Pharmacy

1

ObjectivesThe educator will :• Become familiar with information regarding popular

supplements• Become familiar with information regarding the

pharmacology of supplements, including theorized mechanism of action, side effects, and drug interactions

• Become familiar with appropriate references to evaluate dietary supplements

Which Agents?

• Benfotiamine• Berberine• Cinnamon • Cranberry

• Hibiscus• Magnesium• Mulberry• Vinegar

CoQ10

Challenge: What may decrease Vit B levels?

• ETOH use• DM• Metformin• All of the above?

DJ

• DJ is a 51 y/o male with type 2 DM that is asking questions about his medications. He has DM and is having problems with burning feet at night. He can’t stand the sheets on his feet at night.

Benfotiamine• Thiamine pro-drug; fat soluble form of Vit B1 (better absorbed)

• Mechanism of action Enhances transketolase activity (rate-limiting enzyme of pentose

phosphate pathway)• Inhibits major pathways involved in damage (PKC, AGE,

hexosamine)• Blocks hyperglycemia-induced activation of NF- кß• Normalizes cell division rates• apoptosis

Neuropathy: Pathophysiology

Nature 2001;414:813-20Diabetes 2005;54:1615-25

PARP

Glutathione

TGFβ, PAI-1

Vasodilators VasoconstrictorsActivates NFK-B

ModifiesProteins involvedin gene transcription,Changes signaling

Benfotiamine• Thiamine pro-drug; fat soluble form of Vit B1 (better absorbed)

• Mechanism of action Enhances transketolase activity (rate-limiting enzyme of pentose

phosphate pathway)• Inhibits major pathways involved in damage (PKC, AGE,

hexosamine)• Blocks hyperglycemia-induced activation of NF- кß• Normalizes cell division rates• apoptosis

Benfotiamine

• Side effects Potential allergies but unlikely

• Drug interactions ( thiamine) Metformin, diuretics Antibiotics, OCPs, phenytoin, chemo

• Herb interactions ( thiamine) Horse tail Betel nut

Benfotiamine – Clinical Studies• RDBPCT in 165 pts with T1 and T2 DM• 300 mg, 600 mg, or PL daily (in divided doses) for

6 weeks• Evaluated neuropathy symptom scores, total

symptom scores, and vibration sensation• Evaluated ITT and per protocol • Improved NSS in ITT and PP but significant only in

the per protocol group

Exp Clin Endocrinol Diabetes;2008;116:600-605

Benfotiamine: Clinical Studies

-1.4

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

Exp Clin Endocrinol Diabetes;2008;116:600-605

BF 600 mg BF 300 mg Placebo-1.35 -0.91 -0.63

Neuropathy Symptom Score (5-9) ITT

*p=0.055 between groups

Benfotiamine: Clinical Studies

-1.6

-1.4

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

Exp Clin Endocrinol Diabetes;2008;116:600-605

BF 600 mg BF 300 mg Placebo-1.47 -0.79 -0.67

Neuropathy Symptom Score (5-9) PP

*p=0.033 between groups

Benfotiamine: Clinical Studies• N=40 T2 DM pts randomized to 3 mo of 300 mg/day of thiamine or placebo1 • UAE ↓ to 30.1 mg/24h on thiamine and ↓ to 35.5 mg/24h on placebo

(P<0.01)

• N=82 T2DM randomized to 3 mo of 900 mg/day of BF or placebo2 • UAE ↓ by 18 mg/24 h (72) after 12 wks on BF; by 1 mg/24 on Pl (P=0.36); no

impact on kidney tubule damage marker

• Differences in the two studies:– Lower baseline UAE (45 vs 90) in first study and not all on ACEIs/ARBs– Perhaps BF is more appropriate earlier in nephropathy

1 Diabetologia 2009;52:208-122 Diabetes Care 2010;33:1598-1601

Benfotiamine: Summary• BF, thiamine pro-drug, enhances transketolase and blocks major

biochemical pathways implicated in complications • Emerging evidence: neuropathy, nephropathy• Retinopathy: murine tissue, human cells (prevents pericyte apoptosis)• Combined with ALA has shown benefit in experimental models of

complication generating pathways• Dose is 120-600 mg/day in divided doses; dose-related benefits• Benign side effect profile• Many drugs may decrease thiamine levels

Should persons on metformin or diuretics or other drugs take this supplement?

KC

• KC is a 56 y/o male who wants to control his blood glucose and hyperlipidemia in a more “natural” way. He states he is currently thinking about using a natural product to treat his elevated glucose and LDL.

Berberine• Coptis chinensis (Huanglian or French)• Isoquinoline alkaloid

Ingredient of goldenseal, goldthread, European barberry, tree tumeric

• Uses Antibiotic, antidiarrheal Discovered to have BG/lipid lowering effects

• Mechanism of action ↑ glucose stimulated insulin secretion Facilitates glut-4 transport systems Alpha glucosidase inhibitor activity

Berberine

• Side effects Constipation Kernicterus; do not use in pregnancy!

• Drug interactions Inhibits CYP 3A4 (↑ SDCs of CyA, certain statins) P-glycoprotein modulator (caution with chemo, azoles,

verapamil/diltiazem, some protease inhibitors) Additive effects with diabetes drugs?

Berberine• RDBPCT in 116 newly diagnosed T2DM with dyslipidemia • Given 0.5 gm bid or placebo x 3 months

Ber Pl pFPG BL 126 mg/dL 122 mg/dLFPG End 101 115 <0.0001

PPG BL 216 mg/dL 220 mg/dLPPG End 160 198 <0.0001

A1C BL 7.5% 7.6%A1C End 6.6 7.3 <0.0001

J Clin Endocrinol Metab 2008;93:2559-65

BerberineBer Pl p

Wt BL 68.7 kg 71.8 kgWt End 66.4 70.5 <0.001

TC BL 204 mg/dL 207 mg/dLTC End 167 203 <0.0001

TG BL 221 mg/dL 174 mg/dLTG End 142 181 0.001

LDL BL 124 130LDL End 98 125 <0.0001

J Clin Endocrinol Metab 2008;93:2559-65

Berberine• RCT in 2 groups of T2DM pts – newly diagnosed and poorly

controlled (Ber or Met; Ber + other agents)• Gp A: 0.5 gm tid or metformin 500 mg tid x 3 months (N=36)

Ber MetFPG BL 191 mg/dL 179 mg/dLFPG End 124 p<0.01 129 p<0.01

PPG BL 357 mg/dL 370 mg/dLPPG End 199 p<0.01 232 p<0.01

A1C BL 9.5% 9.2%A1C End 7.5 p<0.01 7.7 p<0.01e.g., berberine = metformin

Metabolism Clin Exper 2008;57:712-17

Berberine• Gp B: 0.5 gm tid + other agents (insulin or orals) x 3 months• N=45

Ber + Other AgentsFPG BL 173 mg/dLFPG End 137 p<0.001

PPG BL 266 mg/dLPPG End 194 p<0.001

A1C BL 8.1%A1C End 7.3 p<0.001

Metabolism Clin Exper 2008;57:712-17

Berberine - Summary• Alkaloid contained in several different plants• Has insulin sensitizing and AGI activity• May ↑ SDCs of drugs metabolized by CYP 3A4

(CyA, some statins, CCBs, etc.)• Constipation is main side effect• Should not be used in pregnancy• Has shown benefit on A1C, FPG, PPG, lipids,

weight, and even BP

ELEL is a 52 y/o perimenopausal female who comes to the clinic. She is taking simvastatin 20 mg daily and lisinopril 20 mg daily. She states she has recently been diagnosed with “T2DM.” She does not want to take any more medications and is asking about using cinnamon.

Cinnamon• Two major types:

Cinnamomum verum (true cinnamon) Cinnamomum aromaticum (synonym

Cinnamomum cassia)• The tree grows in tropical climates• The bark is used medicinally• Used for GI complaints and for flavoring

http://www.theepicentre.com/Spices/cassia.html.

Cinnamon• Active Ingredients1

Polyphenolic polymers (hydroxychalcone) Active constituent may be related to procyanidin type-

A polymers• Mechanism1,2,3

insulin sensitivity cell/tissue glucose uptake Glycogen synthesis Delayed gastric emptying May decrease PPG

1 J Am Coll Nutr 2001;20:327-36 2 Am J Health-Syst Pharm 2007;64:1033-353 Diabetes, Obesity, Metabolism 2009;11:1100-13.

Cinnamon• Side effects1

Topical allergic reactions• e.g., contact dermatitis

Rosacea• Drug Interactions1

May blood glucose if combined with glucose lowering agents

Anticoagulants2 • A coumarin-type component warrants caution

1 The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines2 Am J Health-Syst Pharm 2007;64:1033-35

Cinnamon: Meta Analysis• Meta analysis of 5 RPCT clinical trials1

N = 282 Follow–up: 5.7 to 16 weeks Dose – 1 to 6 g/day of cinnamon (cassia)

• No significant decrease in mean A1C but:1

FBG: - 17 mg/dL TC: - 9.6 mg/dL LDL: - 4.7 mg/dL TGs: - 28.4 mg/dL HDL: + 1.6 mg/dL

• Under-powered (may need 1200-7000 persons)

1 Diabetes Care 2008;31:41-42

Cinnamon

• RPCT of N=109 T2DM pts with A1C > 7% that took 1 g daily of C. Cassia for 90 days Pts on oral agents and/or insulin

Cinnamon PlaceboA1C BL 8.47% 8.28%A1C End 7.64 p<0.001 7.91 p< 0.04 vs placebo

J Am Board Fam Med 2009;22:507-12

Cinnamon - Summary• Cinnamon decreases fasting glucose and lipids and meta

analysis shows benefit is not significant• 2009 study indicates it may be of greater benefit than

thought, but 2010 study in 58 T2DM persons showed A1C ↓ 0.36% from baseline after 3 months (2 gm/day) vs 0.12% increase in Pl (p=0.002) (Diab Med 2010;27:1159-67)

• Procyanidin type-A polymers are thought to be the active ingredient and it may enhance insulin sensitivity

• May also delay gastric emptying and decrease postprandial glucose

• Side effects are benign and there are no known interactions Caution is warranted with concomitant anticoagulants

• The dose is 1-6 g/day

JF JF is a 44 y/o female who has T2DM and has

recently been diagnosed with hyperlipidemia. She does not want to take a “statin” because “it may cause liver toxicity.” She also struggles with frequent UTIs.

Cranberry• Vaccinium macrocarpon• Part used – ripe fruit• Close relative of American blueberry, Europen

bilberry

Cranberry

• Uses UTIs Lipid lowering?

• Chemical constituents Nondialyzable polymeric compound Rich in benzoic acid, which is excreted as hippuric acid

in the urine (although this is not its MOA) Fructose Juice contains resveratrol

Cranberry• Mechanism

Polymeric compound inhibits bacterial adhesion and inhibits adherence of E coli to cells lining bladder wall

Unique theorized effect in lipid modulation • in hepatic cholesterol uptake through induction of

LDL receptor expression in hepatocytes • intestinal cholesterol absorption because

cranberry binds bile acids and fecal cholesterol excretion

Cranberry• Adverse Effects

GI - diarrhea High sugar content may affect diabetes; have patients use sugar

free product Calcium oxalate renal stones?

• Drug interactions Warfarin?

• Flavonoids in cranberry may inhibit CYP2C9 • Several case reports (includes new case with cranberry sauce)

Cranberry

• 1994 RDBPCT in 153 elderly women Women prone to UTIs Measured bacteriuria + WBCs at baseline

and periodically Measured probability of change from

bacteriuric-pyuric to non-infected

JAMA 1994;271:751-54

Urine Samples Each Month With Bacteriuria plus Pyuria for Cranberry or Placebo

Infe

cte

d U

rine

Sa

mp

les,

%

Time, MonthsJAMA 1994;271:751-54

Cranberry• Cranberry does decrease bacteriuria/pyuria, but it takes

about 4-8 weeks to see change• Average 1 mo probability of change from bacteriuric-pyuric to

non-infected Cranberry – 0.54 Placebo – 0.28

• Average 1 mo probability of change from non-infected to bacteriuric-pyuric Cranberry – 0.09 Placebo – 0.12

JAMA 1994;271:751-54

Cranberry - Cochrane Evaluation• Identified 10 studies with RCT or quasi RCT

5 were crossover 5 were parallel 7 compared cranberry/cranberry-ligonberry

with Pl, juice or water 4 compared cranberry tablets with Pl

• N=1049

Cochrane Database Syst Rev 2008

Cranberry - Cochrane Evaluation• Results analyzed for:

Pts with h/o recurrent UTIs Elderly Pts requiring intermittent catheterization Pregnant women Pts with indwelling catheter or urinary tract abnormality

• Also did meta-analysis of 4 parallel studies (N=665)• For meta analysis: RR of UTIs at 12 mo with

cranberries vs Pl/Control: 0.65 (95% CI 0.47-0.92; p=0.01)

Cochrane Database Syst Rev 2008

Cranberry - Cochrane Evaluation• Cranberry more effective in:

Women vs elderly men and women Women with recurrent UTIs

• Less effective in those requiring catheterization• Use had to be at least 1 month to reduce

recurrent UTIs• Studies had high withdrawal rates

Cochrane Database Syst Rev 2008

Cranberry – Effect on Lipids in T2DM

• RDBPCT in 30 persons with T2DM on oral agents: 16 males, 14 females, mean age 65 y/o Given cranberry extracts 500 mg tid after meals or

placebo x 12 wks• Evaluated changes in lipids, BG, CRP, UAE• Results for lipids:

LDL from 127 mg/dL to 112 mg/dL (Cran) LDL from 127 mg/dL to 123 mg/dL (Pl) No significant change in TC, TGs, or HDL

Diabet Med 2008;25:1473-7

Cranberry – Effect on Lipids in T2DM

• Changes in BG and A1C (NS) FBG from 160 mg/dL to 149 mg/dL (Cran) FBG from 149 mg/dL to 142 mg/dL (Pl) A1C from 8.1% to 7.7% (Cran) A1C from 8% to 7.9% (Pl)

• No changes in CRP, UAE

Diabet Med 2008;25:1473-7

Cranberry - Summary

• Cranberry juice/tablets may be used to prevent UTIs• May have a role in lipid profile in DM • Devoid of side effects - caution in patients who have

diabetes with juice products• Caution:

Patients on warfarin Recurrent calcium oxalate stones

• Dose is 300 mL/day all at once or in divided doses; may use equivalent dose of tablets or capsules to decrease sugar/calorie content

Hibiscus (Hibiscus sabdariffa L.)• “Agua de Jamaica” “Karkade” “Sour tea”• Part used: calyx• Uses: BP, liver disease, fever• Active ingredients: anthocyanins

Delphidin-3-sambubiosides Cyanidin-3-sambubiosides

• Mechanism:• ACE inhibition• Vasorelaxation (CCB-like effect?)• Diuretic

Hibiscus (Hibiscus sabdariffa L.)

• Adverse effects Bitter taste Hepatic, renal function assessed in short-

term trials and no problems reported

• Drug interactions ↓ elimination half-life of APAP ↓ elimination of diclofenac Additive effects in combo with ACE Is

Hibiscus: Effects on BP in T2DM• DBRCT in 53 T2DM persons with mild HTN (<160/100

mm Hg; not on BP meds) N=27 on Sour Tea N=26 on Black Tea x 1 mo Given one tea sachet and added 240 mL of boiling water

(allowed to steep 20-30 min)

• SBP Results (mm Hg)Tea BL 4 weeks P (vs BL)ST 134.4 112.7 <0.001BT 118.6 127.3 0.002

P < 0.001 for ST vs BT

Results not significant for DBP

J Hum Hypertens 2009;23:48-54

Hibiscus: Effects on Lipids in T2DM• DBRCT in 53 T2DM persons (not on antilipidemics)

N=27 on Sour Tea; N=26 on Black Tea x 1 mo Given one tea sachet and added 240 mL of boiling water

(allowed to steep 20-30 min)

• Lipid Results (mg/dL)Sour Tea Black TeaBL 4 wks BL 4 wks P (ST vs BT)

LDL 137.5 128.5 124.9 130.1 0.003HDL 48.2 56.1 46.2 52.01 0.6TG 246.1 209.2 247.5 247.8 0.09

J Alt Compl Med 2009;15:899-903

Hibiscus - Summary• Commonly used product• Studies evaluating use lack optimal design• Best study is use in mild HTN; better effect on SBP

than DBP• Has been compared to ACEIs (less effective)• Studies don’t do a good job of reporting SEs• More study is needed

Magnesium• Cofactor for enzymes in

glucose metabolic pathways, phosphorylation reactions

• Hypomagnesemia: Diminished insulin action Insulin resistance, T2DM

• ADRs – GI, hypermagnesemia in renal dysfunction

• Mg depleters – PPIs, diuretics, steroids, digoxin, beta-2 agonists

• Drug interactions -↓ BP with CCBs, ↑ Mg with K-sparers; may impair absorption of tetracyclines, FQs, Ca, bisphosphonates

• Benefit is varied

Natural Medicines Comprehensive Database 12th ed. Stockton, Calif.,

Therapeutic Research Faculty, 2010

Magnesium

• Meta Analysis of 9 DBRCTs N=370 persons with T2DM taking 360 mg/d for 4-16 wks

(median duration 12 wks)

• Results FBG ↓ 10 mg/dL vs control (95% CI -1.1 to -0.01; p=0.03) A1C ↓ 0.31% vs control (95% CI -0.81 to 0.19; p=0.22) HDL ↑ 3 mg/dL (95% CI 0.03 to 0.14; p=0.001) No effects on other lipids, BP, or weight No severe ADRs; only GI side effects

Diabet Med 2006;23:1050-56

Magnesium and Insulin Resistance• RCT of persons of overweight, insulin resistant,

normomagnesemic persons N=25 randomized to Mg aspartate HCl 365 mg; 22 to Pl x 6 mo

• Results Mg levels ↑ but not significantly in Mg group (0.898 to 0.922;

p=0.07) ISI HOMA ↓

3.488 to 2.974 in Mg group 2.9 to 3.713 in Pl group (p=0.0376 for Mg vs Pl)

FPG also ↓ 91 to 86 mg/dL in Mg group 87 to 90 mg/dL in Pl group (p=0.02 for Mg vs Pl)

Diabetes Obes Metab 2011;13:281-84

Magnesium - Summary• Highly used supplement• Many DM pts consume insufficient foods containing Mg – green, leafy

vegetables, grains/nuts, meats, dairy products• Many persons don’t meet RDA for Mg (320 mg/day for women, 420

mg/day for men)• Magnesium may improve insulin resistance and ↓ fasting glucose in

overweight, insulin resistant persons• 15% risk reduction for T2DM with 100 mg/day of Mg• Magnesium may ↓ fasting glucose and ↑ HDL in T2DM• Less neuropathy in T1DM• Mg gluconate or chloride cause less diarrhea; 50 mL Mg Cl (50g/1L of sol’n)• Monitor renal function and potential drug interactions

QZ

QZ is a 49 y/o Thai female with hypertension. She has recently been diagnosed with type 2 diabetes and she is reluctant to start Western medications. She would like to use mulberry since this a familiar product.

Mulberry• Morus alba• Proprietary leaf extract is used for DM• Active ingredients

1-deoxynojirimycin Fagomine Antioxidants (Mulberries contain resveratrol)

• Mechanism of action 1-deoxynojirimycin is a potent alpha glucosidase inhibitor Fagomine induces insulin secretion Antioxidants ↓ lipid peroxidation

Mulberry• Side effects (similar to AGI)

GI side effects – nausea, fullness, bloating, abdominal pain

HA• Drug interactions

Additive BG lowering?

Mulberry• 20 persons (10 normal; 10 with T2DM [not on

AGIs) randomized to 1 gm mulberry leaf extract or placebo and given a 75 gm sucrose challenge BG fingersticks checked over 120 min in controls and

over 240 min in T2DM pts Hourly H2 measurements taken x 8 h (determines

sucrose [CHO] malabsorption)• Sucrose challenge repeated in one week and

persons randomized to opposite treatment

Diabetes Care 2007;30:1272-74

Mulberry• Results

Mean increase in BG: Controls – 15 mg/dL with mulberry; 22 mg/dL with placebo (p=0.005) T2DM - 42 mg/dL with mulberry; 54 mg/dL with placebo (p=0.002)

Breath H2 concentrations Greater in mulberry vs placebo groups (p<0.01; results not given) Sucrose malabsorption in controls with mulberry: 12 gm Sucrose malabsorption in T2DM with mulberry: 16 gm

Diabetes Care 2007;30:1272-74

Mulberry• 12 persons with T2DM [on meds) given a mixture

of mulberry tea and propolis extract (Quapolis) 0.7 mL tid x 30 days Blood samples taken before and after the test period FBG and A1C measured at baseline and 30 days

Results FBG ↓ from 202.8 mg/dL to 129.2 mg/dL (p=0.0019) A1C ↓ from 7.8 to 7% (p=0.0063)

Focus Alternat Complement Ther 2003;8:4524-5

Mulberry• N=24 pts with T2Dm randomized to mulberry or glibenclamide x 30

days D/C previous meds Evaluated glucose, lipids

• ResultsGlibenclamide Mulberry

BL End BL End Mulb (vs BL)FPG (mg/dL) 154 142 153 110 p < 0.01A1C (%) 12.5 12.4 12.5 11.2LDL (mg/dL) 103 96 102 79 p < 0.01HDL (mg/dL) 50 51 50 59 p < 0.01TGs (mg/dL) 200 180 200 68 p < 0.01

Clinica Chimica Acta 2001;314:47-53

Mulberry - Summary• Mulberry leaf extract is widely used in Asia for DM• MOA: AGI activity, increased insulin secretion, antioxidant

activity• ADRS: Mostly GI• Drug interactions not noted thus far – similar to AGI?• Tea combinations being used (black, green, mulberry tea)• Benefit may be ↓ CHO absorption and possibly ↓ weight,

but further study is needed

VRVR is a patient with diabetes that is very tired of taking so many different medications. She is interested in evaluating foods or diets patterns that may help. She has investigated different supplements but finds they are very expensive. She is asking about using a cheap alternative that she has heard of – vinegar.

VinegarIngredients/MOA• Acetic acid• Mechanism of Action

May delay gastric emptying May inhibit disaccharide

activity (not mono-sugars) blocking complete digestion of starches

May help promote muscle glucose uptake

Acetic acid may alter the glycolysis, hepatic gluconeogenic cycle

Side Effects/Drug Interactions• Side effects?

GI? Dental enamel harmed? Hypokalemia? Problem with hypoglycemia if

delay gastric emptying in person with gastroparesis?

• Drug interactions? Absorption of drugs affected? Digoxin toxicity if ↓ K

Diabetes Res Clin Pract 2009;84:e15-17Diabetes Care 2007;30:2814-15

Vinegar Study RDB cross over study evaluating effects of vinegar in

4 different trials (1,2,3,4) of separate populations N=38 total; only trial 4 had T2DM pts

Standardized meal evening prior to testing and then fasted > 10 hours

FBG measured then assigned to apple cider (or red raspberry) vinegar (V) or placebo, followed by standard bkfst meal

Ate standard breakfast meal (bagel/juice) then 2h OGTT (in trials 1,2,4)

Trial 3 had dextrose solution (75 gm glucose)

Ann Nutr Metab 2010;56:74-79

Vinegar• Trial 1 – 4 test drinks (1 wk

intervals): 20, 10, 2 gm V or Pl with test meal and 2-h PPG checked

• Trial 2 – small bkfast then 3 diff tx at 1 wk intervals V or Pl 2 min before test meal

(bagel/juice) then checked 2h PPG

20 gm with small bkfast then BG checked 5 hrs later

Do vinegar effects persist 5 hrs?

• Trial 3 – 2 diff tx at 1 wk intervals: 20 gm V or Pl, 2 min before

“dextrose” then 2h PPG checked• Trial 4 – 3 diff tx at 1 wk

intervals: 20 gm V V pill Pl 2 min before meal then 2h

PPG

Ann Nutr Metab 2010;56:74-79

Vinegar Study - Results Trial 1

10 gm vinegar ↓ PPG 23-28% (p=0.05 vs 2 gm or Pl) 20 gm ↓ PPG only 6-12%

Trial 2 20 gm V 2 min before test meal then 2 h PPG ↓ BG 19% (vs Pl) (p=0.169) If V given 5 hrs earlier, no impact

Trial 3 20 gm V 2 min before “dextrose” or Pl: 2 h PPG 90% higher with V (p=0.059)

Trial 4 20 gm V or V pill or Pl 2 min before meal: 2 h PPG ↓ 13-17% with V vs V pill

or placebo (p=0.0097)• Author’s conclusions – V ↓ PPG 20%; doesn’t work if given 5 hours earlier;

does not work on monosaccharide

Ann Nutr Metab 2010;56:74-79

Vinegar - Summary Vinegar has variety of possible mechanisms

Slows gastric emptying, inhibit disaccharide activity (not monosaccharides), block starch uptake, promote muscle glucose uptake

Apple cider vinegar more effective than vinegar tabs Per study in T2DM: Small effect on ↓ fasting glucose and A1C Benefit may be more for PPG lowering when taken with a

meal – this effect shown also in T1DM Persons with gastroparesis may not be candidates More study needed to determine side effects, drug

interactions

CoQ10• Vitamin-like substance; ↑ ATP

production; Scavenges OFRs; Membrane stabilizer

• Small studies have resulted in slight ↓ in FBG and A1C (NS)

• Symptomatic HF improvement; may ↓ BP, improve angina, Parkinson’s, ↓ statin-induced myopathy

• Long-term safety - 6 years• Use soybean oil formulation

• Better absorption

• Side effects GI, rash, increased LFTs

• Drug interactions Warfarin, statins, BP meds Adriamycin® (less cardiac

toxicity but less efficacy?)• Some evidence for use in

several diseases• DM dose – 100-200 mg/d• Natural Standard: Grade “D”

Natural Medicines Comprehensive Database 12th ed.

Stockton, Calif., Therapeutic Research Faculty, 2010

Appropriate References• Natural Standard (www.naturalstandard.com)

Multidisciplinary research collaboration that uses evidence-based criteria to evaluate different products and enable decision-support

Excellent job of appraising original research on herbs/supplements Monographs reviewed by Western-trained clinicians and CAM

practitioners Evidence grade

• A – Strong positive scientific evidence• B – Positive scientific evidence• C – Unclear scientific evidence• D – Negative scientific evidence• F – Strong negative scientific evidence

Appropriate References• Natural Medicines Comprehensive Database

(www.naturaldatabase.com) Maintained by Pharmacist’s Letter/Prescriber’s Letter Approximately 1100 ingredients reviewed in evidence-based

monographs Index containing over 38,000 brand names Section on other alternative therapy modalities – acupuncture,

balneotherapy, colonic irrigation, aromatherapy, shiatsu, reiki, etc. USP-verified product names References!!

Appropriate References• The Cochrane Collaboration – http://www.cochrane.org

International organization providing up to date information about health care information interventions

Cochrane Library has regularly updated databases and systematic reviews of different treatments

Regularly updated evidence-based information• National Center for Complementary and Alternative Medicine

(NCCAM – free) - http://nccam.nih.gov Information for clinicians and the public Access information under “Research, Clinical Trials, Training, and

Health Information”

Appropriate Patient References

• FDA websites Tips for the Savvy Supplement User –

http://www.cfsan.fda.gov/~dms/ds-savvy.html

Tips for Older Dietary Supplement Users – http://www.fda.gov/Food/DietarySupplements/ConsumerInformation/ucm110493.htm

MedWatch – www.fda.gov/medwatch

• Read FDA 101: Dietary supplements http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/ucm050824.pdf

Supplement Use: Guiding Patients Read FDA 101: Dietary supplements –

http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/ucm050824.pdf

• Determine why you want to use a supplement• What are your goals for supplement – be specific• Consider that products may cause side effects or drug interactions• Select single-ingredient products• Discuss use with your provider to determine appropriate length of

treatment Don’t stop or start without discussion since this may affect the other

medications being taken• Don’t stop taking your other medications• Don’t share the products• Consider that you must still eat healthy and exercise

How to Select a Product

• Choose a reputable manufacturer – appropriate information on a label?

• How to evaluate information on the internet – http://ods.od.nih.gov/(Click on How to evaluate health information on the internet)

• Consider use of testing services USP – http://www.usp.org Consumer Lab – http://www.consumerlab.com NSF International – http://www.nsf.org/consumer Natural Products Association – http://www.npainfo.org/

Counseling Patients• First be respectful of patients beliefs• Provide evidence-based information• Present the patient with target goals and evidence of

potential benefit or lack of benefit• Consider potential side effects and drug interactions• Help patient evaluate whether product brand is

appropriate• Emphasize role of conventional medications• Be informed and supportive