Transcript What`s New? - American Association of Diabetes Educators of Utah

Dietary Supplements
and Diabetes:
What’s New?
Laura Shane-McWhorter, PharmD,
BCPS, BC-ADM, CDE, FASCP, FAADE
University of Utah College of Pharmacy
1
Objectives
The 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?
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Benfotiamine
Berberine
Cinnamon
Cranberry
CoQ10
Hibiscus
Magnesium
Mulberry
Vinegar
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 (ratelimiting 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

Glutathione

TGFβ, PAI-1

Vasodilators

Vasoconstrictors
Activates NFK-B
 PARP
Nature 2001;414:813-20
Diabetes 2005;54:1615-25
Modifies
Proteins involved
in gene
transcription,
Changes signaling
Benfotiamine
• Thiamine pro-drug; fat soluble form of
Vit B1 (better absorbed)
• Mechanism of action
 Enhances transketolase activity (ratelimiting 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
Neuropathy Symptom Score (5-9) ITT
0
-0.2
-0.4
-0.6
*p=0.055 between groups
-0.8
-1
-1.2
-1.4
BF 600 mg
-1.35
BF 300 mg
-0.91
Placebo
-0.63
Exp Clin Endocrinol Diabetes;2008;116:600-605
Benfotiamine: Clinical Studies
Neuropathy Symptom Score (5-9) PP
0
-0.2
-0.4
-0.6
-0.8
*p=0.033 between groups
-1
-1.2
-1.4
-1.6
BF 600 mg
-1.47
BF 300 mg
-0.79
Placebo
-0.67
Exp Clin Endocrinol Diabetes;2008;116:600-605
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;52:208-12
2 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
p
FPG BL
FPG End
126 mg/dL
101
122 mg/dL
115
<0.0001
PPG BL
PPG End
216 mg/dL
160
220 mg/dL
198
<0.0001
A1C BL
A1C End
7.5%
6.6
7.6%
7.3
<0.0001
J Clin Endocrinol Metab 2008;93:2559-65
Berberine
Ber
Pl
p
Wt BL
Wt End
68.7 kg
66.4
71.8 kg
70.5
<0.001
TC BL
TC End
204 mg/dL
167
207 mg/dL
203
<0.0001
TG BL
TG End
221 mg/dL
142
174 mg/dL
181
0.001
LDL BL
LDL End
124
98
130
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
Met
FPG BL
FPG End
191 mg/dL
124 p<0.01
179 mg/dL
129 p<0.01
PPG BL
PPG End
357 mg/dL
199 p<0.01
370 mg/dL
232 p<0.01
A1C BL
A1C End
9.5%
7.5 p<0.01
9.2%
7.7 p<0.01
e.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 Agents
FPG BL
FPG End
173 mg/dL
137 p<0.001
PPG BL
PPG End
266 mg/dL
194 p<0.001
A1C BL
A1C End
8.1%
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
EL
EL 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 typeA 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;64:1033-35
3 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 Medicines
2 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
A1C BL
A1C End
Cinnamon
Placebo
8.47%
7.64 p<0.001
8.28%
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
JAMA 1994;271:751-54
Time, Months
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 noninfected 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 shortterm 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
ST
BT
BL
134.4
118.6
4 weeks
112.7
127.3
P (vs BL)
<0.001
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)
LDL
HDL
TG
Sour Tea
BL
4 wks
137.5 128.5
48.2 56.1
246.1 209.2
Black Tea
BL
4 wks
124.9 130.1
46.2 52.01
247.5 247.8
P (ST vs BT)
0.003
0.6
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
• Mg depleters – PPIs, diuretics,
glucose metabolic
steroids, digoxin, beta-2
pathways, phosphorylation
agonists
reactions
• Drug interactions -↓ BP with
• Hypomagnesemia:
CCBs, ↑ Mg with K-sparers; may
impair absorption of
 Diminished insulin action
tetracyclines, FQs, Ca,
 Insulin resistance, T2DM
bisphosphonates
• ADRs – GI,
hypermagnesemia in renal • Benefit is varied
dysfunction
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
• Results
Glibenclamide
BL
End
FPG (mg/dL) 154 142
A1C (%)
12.5 12.4
LDL (mg/dL) 103 96
HDL (mg/dL) 50
51
TGs (mg/dL) 200 180
Mulberry
BL
End
153 110
12.5 11.2
102 79
50
59
200 68
Mulb (vs BL)
p < 0.01
p < 0.01
p < 0.01
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
VR
VR 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.
Vinegar
Ingredients/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:e15-17
Diabetes 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)
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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
• 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”
• Better absorption
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)
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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
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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