Dietary Supplements and Diabetes: What

1
Dietary Supplements and DiabetesWhats New?

• Laura Shane-McWhorter, PharmD,
• BCPS, BC-ADM, CDE, FASCP, FAADE
• University of Utah College of Pharmacy

2
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

3
Which Agents?

• Benfotiamine
• Berberine
• Cinnamon
• Cranberry

• Hibiscus
• Magnesium
• Mulberry
• Vinegar

CoQ10
4
Challenge What may decrease Vit B levels?

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

5
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 cant stand the sheets on his feet at night.

6
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- ?ß
• Normalizes cell division rates
• ? apoptosis

7
Neuropathy Pathophysiology
? Glutathione ? TGFß,
PAI-1 ? Vasodilators
? Vasoconstrictors Activates NFK-B
Modifies Proteins involved in gene
transcription, Changes signaling
? PARP
Nature 2001414813-20 Diabetes 2005541615-25
8
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- ?ß
• Normalizes cell division rates
• ? apoptosis

9
Benfotiamine

• Side effects
• Potential allergies but unlikely
• Drug interactions (? thiamine)
• Metformin, diuretics
• Antibiotics, OCPs, phenytoin, chemo
• Herb interactions (? thiamine)
• Horse tail
• Betel nut

10
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 Diabetes2008116600-605
11
Benfotiamine Clinical Studies
Neuropathy Symptom Score (5-9) ITT
p0.055 between groups
BF 600 mg BF 300 mg
Placebo -1.35 -0.91
-0.63
Exp Clin Endocrinol Diabetes2008116600-605
12
Benfotiamine Clinical Studies
Neuropathy Symptom Score (5-9) PP
p0.033 between groups
BF 600 mg BF 300 mg
Placebo -1.47 -0.79
-0.67
Exp Clin Endocrinol Diabetes2008116600-605
13
Benfotiamine Clinical Studies

• N40 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 (Plt0.01)
• N82 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 (P0.36) 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 200952208-12 2 Diabetes Care
2010331598-1601
14
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?

15
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.

16
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

17
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?

18
Berberine

• RDBPCT in 116 newly diagnosed T2DM with
  dyslipidemia
• Given 0.5 gm bid or placebo x 3 months
• Ber Pl p
• FPG BL 126 mg/dL 122 mg/dL
• FPG End 101 115 lt0.0001
• PPG BL 216 mg/dL 220 mg/dL
• PPG End 160 198 lt0.0001
• A1C BL 7.5 7.6
• A1C End 6.6 7.3 lt0.0001

J Clin Endocrinol Metab 2008932559-65
19
Berberine

• Ber Pl p
• Wt BL 68.7 kg 71.8 kg
• Wt End 66.4 70.5 lt0.001
• TC BL 204 mg/dL 207 mg/dL
• TC End 167 203 lt0.0001
• TG BL 221 mg/dL 174 mg/dL
• TG End 142 181 0.001
• LDL BL 124 130
• LDL End 98 125 lt0.0001

J Clin Endocrinol Metab 2008932559-65
20
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 (N36)
• Ber Met
• FPG BL 191 mg/dL 179 mg/dL
• FPG End 124 plt0.01 129 plt0.01
• PPG BL 357 mg/dL 370 mg/dL
• PPG End 199 plt0.01 232 plt0.01
• A1C BL 9.5 9.2
• A1C End 7.5 plt0.01 7.7 plt0.01
• e.g., berberine metformin

Metabolism Clin Exper 200857712-17
21
Berberine

• Gp B 0.5 gm tid other agents (insulin or
  orals) x 3 months
• N45
• Ber Other Agents
• FPG BL 173 mg/dL
• FPG End 137 plt0.001
• PPG BL 266 mg/dL
• PPG End 194 plt0.001
• A1C BL 8.1
• A1C End 7.3 plt0.001

Metabolism Clin Exper 200857712-17
22
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

23
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.

24
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.
25
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 200120327-36 2 Am J
Health-Syst Pharm 2007641033-35 3 Diabetes,
Obesity, Metabolism 2009111100-13.
26
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 2007641033-35
27
Cinnamon Meta Analysis

• Meta analysis of 5 RPCT clinical trials1
• N 282
• Followup 5.7 to 16 weeks
• Dose 1 to 6 g/day of cinnamon (cassia)
• No significant decrease in mean A1C but1
• 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 20083141-42
28
Cinnamon

• RPCT of N109 T2DM pts with A1C gt 7 that took 1
  g daily of C. Cassia for 90 days
• Pts on oral agents and/or insulin
• Cinnamon Placebo
• A1C BL 8.47 8.28
• A1C End 7.64 plt0.001 7.91 plt 0.04 vs placebo

J Am Board Fam Med 200922507-12
29
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 (p0.002)
  (Diab Med 2010271159-67)
• 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

30
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.

31
Cranberry

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

32
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

33
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

34
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)

35
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 1994271751-54
36
Urine Samples Each Month With Bacteriuria plus
Pyuria for Cranberry or Placebo
Infected Urine Samples,
Time, Months
JAMA 1994271751-54
37
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 1994271751-54
38
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
• N1049

Cochrane Database Syst Rev 2008
39
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
  (N665)
• For meta analysis RR of UTIs at 12 mo with
  cranberries vs Pl/Control
• 0.65 (95 CI 0.47-0.92 p0.01)

Cochrane Database Syst Rev 2008
40
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
41
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 2008251473-7
42
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 2008251473-7
43
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

44
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

45
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

46
Hibiscus Effects on BP in T2DM

• DBRCT in 53 T2DM persons with mild HTN (lt160/100
  mm Hg not on BP meds)
• N27 on Sour Tea N26 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 lt0.001
• BT 118.6 127.3 0.002
• P lt 0.001 for ST vs BT
• Results not significant for DBP

J Hum Hypertens 20092348-54
47
Hibiscus Effects on Lipids in T2DM

• DBRCT in 53 T2DM persons (not on antilipidemics)
• N27 on Sour Tea N26 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 Tea
• BL 4 wks BL 4 wks P (ST vs BT)
• LDL 137.5 128.5 124.9 130.1 0.003
• HDL 48.2 56.1 46.2 52.01 0.6
• TG 246.1 209.2 247.5 247.8 0.09

J Alt Compl Med 200915899-903
48
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 dont do a good job of reporting SEs
• More study is needed

49
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
50
Magnesium

• Meta Analysis of 9 DBRCTs
• N370 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
  p0.03)
• A1C ? 0.31 vs control (95 CI -0.81 to 0.19
  p0.22)
• HDL ? 3 mg/dL (95 CI 0.03 to 0.14 p0.001)
• No effects on other lipids, BP, or weight
• No severe ADRs only GI side effects

Diabet Med 2006231050-56
51
Magnesium and Insulin Resistance

• RCT of persons of overweight, insulin resistant,
  normomagnesemic persons
• N25 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 p0.07)
• ISI HOMA ?
• 3.488 to 2.974 in Mg group
• 2.9 to 3.713 in Pl group (p0.0376 for Mg vs Pl)
• FPG also ?
• 91 to 86 mg/dL in Mg group
• 87 to 90 mg/dL in Pl group (p0.02 for Mg vs Pl)

Diabetes Obes Metab 201113281-84
52
Magnesium - Summary

• Highly used supplement
• Many DM pts consume insufficient foods containing
  Mg green, leafy vegetables, grains/nuts, meats,
  dairy products
• Many persons dont 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 soln)
• Monitor renal function and potential drug
  interactions

53
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.

54
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

55
Mulberry

• Side effects (similar to AGI)
• GI side effects nausea, fullness, bloating,
  abdominal pain
• HA
• Drug interactions
• Additive BG lowering?

56
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 2007301272-74
57
Mulberry

• Results
• Mean increase in BG
• Controls 15 mg/dL with mulberry 22 mg/dL with
  placebo (p0.005)
• T2DM - 42 mg/dL with mulberry 54 mg/dL with
  placebo (p0.002)
• Breath H2 concentrations
• Greater in mulberry vs placebo groups (plt0.01
  results not given)
• Sucrose malabsorption in controls with mulberry
  12 gm
• Sucrose malabsorption in T2DM with mulberry
  16 gm

Diabetes Care 2007301272-74
58
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 (p0.0019)
• A1C ? from 7.8 to 7 (p0.0063)

Focus Alternat Complement Ther 200384524-5
59
Mulberry

• N24 pts with T2Dm randomized to mulberry or
  glibenclamide x 30 days
• D/C previous meds
• Evaluated glucose, lipids
• Results
• Glibenclamide Mulberry
• BL End BL End Mulb (vs BL)
• FPG (mg/dL) 154 142 153 110 p lt 0.01
• A1C () 12.5 12.4 12.5 11.2
• LDL (mg/dL) 103 96 102 79 p lt 0.01
• HDL (mg/dL) 50 51 50 59 p lt 0.01
• TGs (mg/dL) 200 180 200 68 p lt 0.01

Clinica Chimica Acta 200131447-53
60
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

61
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.

62
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 200984e15-17 Diabetes
Care 2007302814-15
63
Vinegar Study

• RDB cross over study evaluating effects of
  vinegar in 4 different trials (1,2,3,4) of
  separate populations
• N38 total only trial 4 had T2DM pts
• Standardized meal evening prior to testing and
  then fasted gt 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 20105674-79
64
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 20105674-79
65
Vinegar Study - Results

• Trial 1
• 10 gm vinegar ? PPG 23-28 (p0.05 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) (p0.169)
• 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 (p0.059)
• 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
  (p0.0097)
• Authors conclusions V ? PPG 20 doesnt work
  if given 5 hours earlier does not work on
  monosaccharide

Ann Nutr Metab 20105674-79
66
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

67
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, Parkinsons, ? 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
68
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

69
Appropriate References

• Natural Medicines Comprehensive Database
  (www.naturaldatabase.com)
• Maintained by Pharmacists Letter/Prescribers
  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!!

70
Appropriate References

• The Cochrane Collaboration http//www.cochrane.o
  rg
• 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

71
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/Consum
  erInformation/ucm110493.htm
• MedWatch www.fda.gov/medwatch
• Read FDA 101 Dietary supplements
• http//www.fda.gov/downloads/ForConsumers/Consume
  rUpdates/ucm050824.pdf

72
Supplement Use Guiding Patients

• Read FDA 101 Dietary supplements
  http//www.fda.gov/downloads/ForConsumers/Consumer
  Updates/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
• Dont stop or start without discussion since this
  may affect the other medications being taken
• Dont stop taking your other medications
• Dont share the products
• Consider that you must still eat healthy and
  exercise

73
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/

74
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