Appendix Tables 1 and 2 Free

Aloe vera

Diabetes, Obesity:

• Possibly Effective

Hyperlipidemia,

• Prediabetes:

• Not Rated by

• Natural Medicines

Various ingredients^1-3;9

• Aloe gel contains acemannan (polysaccharide similar to guar gum and glycoprotein)

• Aloeresin A

• Phenolic and saponin contents

Various mechanisms^1-3;9

Diabetes:

• Fiber may delay or prevent glucose absorption

• Aloeresin may inhibit α-glucosidases

• Decrease insulin resistance by AMPK activation

• Acemannan may decrease inflammation

• Acemannan may promote benefit through gut microbiota via production of short chain fatty acids

Hyperlipidemia:

• Altered lipid metabolism

• Decreased lipid absorption

Side effects:^1,4-6

• Abdominal pain, diarrhea

• Acute hepatitis

• Thyroid dysfunction

• Possible carcinogenicity

Drug interactions:^1,7

• Possible digoxin toxicity due to potential hypokalemia

• Intraoperative blood loss in surgery patients where sevoflurane was used

• Additive glucose lowering effects with sulfonylureas and insulin

Banaba

Diabetes:

Possibly Effective

Prediabetes:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,3

• Corsolic acid

• Ellagitannins:

  • – Lagerstroemin

  • – Flosin B

  • – Reginin A

Various mechanisms^1,3-4

Diabetes:

• Enhanced glucose transport

• May stimulate glucose uptake

• Insulin-like activity (increased tyrosine phosphorylation of insulin receptor β-subunit)

Side effects:^1,5-7

• Lactic acidosis in renal impairment

• In combination products:

  • – Stomach upset

  • – Dizziness, weakness

  • – Diaphoresis

  • – Palpitations

  • – Tremor

Drug interactions:^1,8

• Possible hypotension if combined with antihypertensives

• Additive glucose-lowering effects with sulfonylureas and insulin

• OATP inhibition may decrease absorption of statins, sulfonylureas, some antihyper-tensives, fluoroquinolones

Berberine

Diabetes,

• Hypertension

• Hyperlipidemia:

Possibly Effective

Obesity, Metabolic

• Syndrome, Non

• Alcoholic Fatty

• Liver Disease

• (NAFLD):

Insufficient Reliable

• Evidence to Rate

Diabetic Nephropathy:

• Not Rated by Natural Medicines

Various mechanisms^1-5

Diabetes:

• Enhanced glucose-stimulated insulin secretion

• Increased insulin receptor expression

• GLUT4 translocation

• α-glucosidase inhibition

• Enhanced AMPK

• Increased GLP-1 activity

• PPARγ receptor activation

• Stimulates gut microbiota

Hyperlipidemia:

• Decreased cholesterol absorption

• Upregulates LDL receptors

• PCSK9 inhibition

Hypertension:

• α-2 agonist activity

• Blocks α adrenergic activity

Diabetic Nephropathy:

• Inhibits aldose reductase

Side effects:^1,2,6

• Abdominal upset, constipation, diarrhea

• Headache

• Muscle pain

• May stimulate uterine contractions

• Kernicterus

Drug interactions:¹

• Increased levels of drugs metabolized by CYP3A4 (cyclosporine, certain statins, and calcium channel blockers)

• Increased levels of drugs metabolized by CYP2C9 (warfarin, losartan)

• Increased levels of drugs metabolized by CYP2D6 (metoprolol, certain tricyclic antidepressants, tramadol)

• Additive glucose-lowering effects with sulfonylureas and insulin

• Additive hypotension if combined with antihypertensives

• Sedation if combined with CNS depressants

Bilberry

Chronic venous

• insufficiency:

Possibly Effective

Diabetes,

• Hypertension,

• Diabetic

• Retinopathy,

• Hypertensive

• Retinopathy,

• Prediabetes,

• Metabolic

• Syndrome:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-5

• Anthocyanosides

• Polyphenols

• Chromium (in bilberry leaf)

• Neomirtilline

Various mechanisms^1-5

Diabetes:

• α-glucosidase inhibition

• May stimulate insulin secretion

• Inhibits glucose uptake

• Antioxidant activity

• Anti-inflammatory effects

Hypertension, Diabetic Retinopathy:

• Vasorelaxation

• Antioxidant activity

• Anti-inflammatory effects

• Improved ocular blood flow

Side effects:^1-5

• Abdominal upset

• Possible hypotension

• Possible hypoglycemia

• Possible bleeding

Drug interactions:¹

• Possible bleeding with antiplatelets/anticoagulants

• Additive glucose-lowering effects with sulfonylureas and insulin

Bitter melon

Diabetes, Prediabetes:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-4

• Momordin

• Charantin

• Momordicin

• Polypeptide-P

• Vicine

Various mechanisms^1-8

Diabetes:

• Tissue glucose uptake; glycogen synthesis

• Enhanced glucose oxidation of Glucose-6-phosphate-dehydrogenase (G6PDH) pathway

• AMPK pathway activation

• α-glucosidase inhibition

• PPARγ receptor activation

• GLUT 4 translocation

Side effects:^1-3

• Gastrointestinal (GI) discomfort

• Hypoglycemic coma

• Favism

• Hemolytic anemia in persons with G6PDH deficiency

• Contains known abortifacients (α and β

• momorcharin)

• Seeds have produced severe hypoglycemia, vomiting, death in children

Drug interactions:^1,9

• Additive glucose-lowering effects with sulfonylureas and insulin

• Increased concentrations of drugs metabolized by p-glycoprotein pathway (linagliptin, diltiazem, verapamil, rivoraxaban, apixaban, vincristine, vinblastine, protease inhibitors) due to inhibition of p-gly-coprotein efflux

Chia

Diabetes, Blood

• Pressure, Metabolic

• Syndrome:

Insufficient Reliable

• Evidence to Rate

Obesity:

Possibly Ineffective

Various Ingredients^1,3,5

• α-linolenic acid

• Fiber

• Protein

• Calcium, Phosphorous, Magnesium, Iron

• Antioxidants:

  • – Chlorogenic acid

  • – Caffeic acid

  • – Quercetin

  • – Kaempferol

  • – Myricetin

Various mechanisms^1,3,5

Diabetes:

• Fiber decreases postmeal glucose

Hypertension:

• Angiotensin converting enzyme inhibition by some constituents

Side effects:^1,8-10

• Gastrointestinal (GI) discomfort

• Allergic reactions

• Possible increase in triglycerides

• Possible increased risk for prostate cancer (α-linolenic acid consumption)

Drug interactions:¹

• None reported

Chromium

Diabetes,

Hyperlipidemia:

Possibly Effective

Obesity, Prediabetes:

Possibly Ineffective

Trivalent chromium^1,2

Various mechanisms^1-8

Diabetes:

• May enhance cellular effects of insulin

• May increase number of insulin receptors

• May increase insulin binding or insulin activation

• Increased tyrosine kinase activity at insulin receptor

• GLUT 4 translocation

• Increased AMPK activity

• Inhibits acetyl-Coenzyme A carboxylase, resulting in decreased malonyl Coenzyme A

Hyperlipidemia

• Suppression of sterol regulatory element binding protein

• Affects lipid metabolism modulation in peripheral tissues

• May inhibit 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-Co-A reductase inhibition)

Side effects:^1,8-12,15

• Gastrointestinal upset

• Excessive intake may lead to renal toxicity, severe systemic illness

• Dermatologic reactions

Drug interactions:^1,8-15

• Additive glucose-lowering effects with sulfonylureas and insulin

• Chromium is depleted by steroids

• Histamine blockers and proton pump inhibitors may block chromium absorption

• Coadministration with zinc depletes absorption of both chromium and zinc

• Increased insulin sensitivity, adiponectin if combined with Vit C or Vit E

• Vit C, NSAIDs increase absorption

• Complexes with ferritin and produces ferritin deficiency

• Decreases levothyroxine levels

• When combined with biotin, decreased hepatic glucose output and gluconeogenesis

Cinnamon

Diabetes:

Possibly Effective

Prediabetes, Obesity:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia,

• Hypertension:

Not Rated by Natural

• Medicines

Various Ingredients^1-5

• Cinnamaldehyde

• Eugenol

• Coumarins

Various mechanisms^1-9

Diabetes:

• Increased insulin receptor phosphorylation and improved insulin signaling

• Increased insulin sensitivity and action

• Increased cell/tissue glucose uptake

• Promotes glycogen synthesis

• α-glucosidase inhibition

• Peroxisome proliferator-activated receptor activation

• May help delay gastric emptying and reduce excess postprandial glucose and triglyceride levels

• GLUT 4 translocation

• AMPK activation

• GLP-1 activity

Hyperlipidemia:

• For lipid lowering: inhibiting hepatic-3-hydroxy-methylglutaryl CoA reductase activity

Hypertension:

• Peripheral vasodilation

Side effects:¹

• Irritation or dermatitis if used topically

• High coumarin content in certain species or products may result in hepatotoxicity, per animal models

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

• Due to a coumarin ingredient, it may theoretically result in bleeding if combined with antiplatelets/anticoagulants

• Possible additive hepatotoxicity if combined with hepatotoxins (acetaminophen, methotrexate, comfrey, chaparral)

Fenugreek

Diabetes:

Possibly Effective

Prediabetes,

• Hyperlipidemia,

• Obesity:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-5

• Saponins (Diosgenin)

• Glycosides

• Seeds contain:

  • – alkaloids (including trigonelline)

  • – 4-hydroxyisoleucine

  • – fenugreekine

Various mechanisms^1-7

Diabetes:

• Delayed gastric emptying

• Slowed carbohydrate absorption

• Glucose transport inhibition

• Increased number of insulin receptors

• Possible stimulation of glucosedependent insulin secretion

• Improved peripheral glucose utilization

Hyperlipidemia:

• Saponins may increase biliary cholesterol secretion, leading to decreased serum lipids.

Side effects:^1-3,8

• Diarrhea, gas

• Uterine contractions; possible miscarriage

• Teratogenicity (cleft palate, spina bifida, hydrocephalus, anencephaly.

• Allergic reactions

Drug interactions:^1,9

• Additive glucose-lowering effects with sulfonylureas and insulin

• May increase anticoagulant effects of antiplatelets/anticoagulants

• Decreased effect of theophylline by decreasing its serum concentrations

Flaxseed

Diabetes,

Hyperlipidemia,

• Hypertension,

• Obesity:

Possibly Effective

Prediabetes, Metabolic

• Syndrome, NAFLD:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-3

• Lignans, including secoisolariciresinol diglucoside, and matairesinol

• Linoleic acid

• Soluble fiber in seed and oil

• α-linolenic acid, a plant omega-3 fatty acid

Various mechanisms^1-3;5,8

Diabetes:

• Soluble fiber slows gastric emptying

• Fiber decreases glucose absorption and postprandial glucose

Hyperlipidemia:

• Fiber in flaxseed increases fecal bile acid elimination

• Modulation of 7 α–hydroxylase and acyl CoA cholesterol transferase

• Decreased production of proinflammatory eicosanoids

Hypertension:

• Alteration of circulating oxylipins

Side effects:¹

• Gastrointestinal upset

• Flax hypersensitivity

• Uncooked flaxseed contains cyanogenic glycosides

• May exert estrogenic effects in pregnancy

• Possible increased risk for prostate cancer (α-linolenic acid consumption)

Drug interactions:¹

• Bleeding if combined with antiplatelets/anticoagulants

• Additive glucose-lowering effects with sulfonylureas and insulin

• Possible hypotension if combined with antihypertensives.

• Possible additive estrogenic or antiestrogenic effect with estrogens.

• May decrease absorption of certain medications, such as acetaminophen, furosemide, or other medications.

• Antibiotics may affect conversion of Secoisolariciresinol diglucoside (SDG) to certain metabolites that may affect flax-seed activity.

Ginseng

Panax Ginseng

• Diabetes,

• Hypertension,

• Prediabetes:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia:

Not Rated by Natural

• Medicines

American Ginseng

Diabetes:

Possibly Effective

Hypertension:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia:

Not Rated by Natural

• Medicines

Various ginsenosides^1-9

• Protopanaxadiol

  • – Rb1

  • – Rb2

  • – Rc

  • – Rd

• Protopanaxatriol

  • – Rg1

  • – Re

  • – Rf

Various mechanisms^1-10

Diabetes:

• Enhance β-cell function

• Modulation of insulin secretion

• May decrease carbohydrate absorption in portal circulation

• May decrease glucose transport and uptake and disposal

Hyperlipidemia:

• May increase lipoprotein lipase activity

Hypertension:

• In vitro may inhibit angiotensin converting enzyme activity

Side effects:^1,2

• Insomnia, headache, restlessness

• Increased blood pressure (inconsistent effect) or increased heart rate

• Mastalgia

• Mood changes, nervousness

• Possible teratogenicity

Drug interactions:^1,2

• Decreased warfarin, diuretic, antihypertensive effectiveness

• Additive estrogenic effects

• Possible increased effects of certain analgesics and antidepressants

• Additive glucose-lowering effects with sulfonylureas and insulin

Gymnema sylvestre

Diabetes, Metabolic

• Syndrome, Weight

• Loss:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-10

• Gymnemic acids (gymnemosides)

• Gymnemasaponins

• Gurmarin

• Stigmasterol

• Betaine

• Choline

Various mechanisms^1,3-10

Diabetes:

• Impairs ability to discriminate “sweet” taste

• Blocks glucose absorption in small intestine

• Increases number of enzymes promoting glucose uptake

• May increase and stimulate β-cells

• May increase insulin release by promoting cell permeability to insulin

Side effects:^1,10

• May cause hypoglycemia

• Toxic hepatitis (per case report)

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

• May induce or inhibit CYP450 2C9 (may affect serum concentration of warfarin or ibuprofen)

• May inhibit CYP 450 1A2 system (may affect serum concentration of some psychiatric medications—some antipsychotics and antidepressants)

• Conflicting information on CYP 450 3A4 inhibition. Some reports state it may inhibit this enzyme and thus increase serum concentrations of some medications (calcium channel blockers, antibiot-ics); other reports state there is no impact

Holy Basil

Diabetes, Obesity:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-2,6-8

• Eugenol

• Ursolic acid

• Apigenin

• Polyphenols

• Caffeic acid

• Chicoric acid

• P-coumaric acid compound

• Zinc

Various mechanisms^1,2,6-8

Diabetes:

• May improve pancreatic β-cell function and thus enhance insulin secretion

• Enhanced activity of enzymes involved in carbohydrate metabolism

  • – glucokinase

  • – hexokinase

  • – phosphofructokinase

• Zinc content may help decrease insulin resistance

Side effects:¹

• May lower thyroxine (worsens hypothyroidism)

• May cause bleeding

• Decreased sperm count and fertility

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

• Possible bleeding with anticoagulants/antiplatelets

• Sedation with phenobarbital sedatives

Honey

Diabetes,

• Hyperlipidemia,

• Obesity:

Insufficient Reliable

• Evidence to Rate

Diabetic Foot Ulcers:

Possibly Effective

Various ingredients^1-5

• Fructose

• Glucose

• Oligosaccharides (such as palatinose)

• Phenolic acids

• Flavonoids

• Proteins

• Amino acids

• Enzymes

• Vitamins

• Fatty acids

Various mechanisms^1-7

Diabetes:

• Fructose:glucose ratio

• Fructose may help stimulate insulin release and secretion

• Hepatic glucose uptake by glucokinase and glycogen synthase activation to promote glycogen synthesis and storage

• Pancreatic antioxidant effects (which may improve pancreatic

• β-cell function and help decrease lipids)

• Prebiotic activity

Obesity:

• Modulates ghrelin and peptide YY

Diabetic Foot Ulcers

• Antimicrobial, anti-inflammatory effects

• 5,8-kDa stimulates immune cell activity

Side effects:¹

• Allergic reactions

• Possible botulism

• Cardiac toxicity if honey source is rhododendrons (grayanotoxins)

• Infection if topical honey is applied to dialysis tubing exit sites

Drug interactions:¹

• Additive effects with anticoagulants/antiplatelets

• Increased absorption of phenytoin

Ivy Gourd

Diabetes:

Possibly Effective

Other Uses:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,3-4

• Beta-carotene

• Triterpenes (leaves)

• Pectin (fruit)

• Fiber

• Protein

• Calcium

• Alkaloids

Various mechanisms^1,3-4

Diabetes:

• Insulin-like activity

• Suppresses elevated levels of enzymes involved in glucose production (glucose-6-phosphatase and lactate dehydrogenase)

• May restore lipoprotein lipase activ-ity.

Side effects:^1,3

• GI upset

• Drowsiness

• Hypoglycemia

• Possible allergic reactions

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

Magnesium

Diabetes,

Hyperlipidemia,

Metabolic Syndrome:

Possibly Effective

Hypomagnesemia:

Effective

Various salts^1,2,5,9

• Sulfate

• Citrate

• Hydroxide

• Oxide

• Chloride

Various mechanisms^1,2,5,9-10

Diabetes:

• Cofactor for enzymes in glucose metabolic pathways and phosphorylation reactions

• Low dietary magnesium may contribute to insulin resistance and type 2 diabetes

Hypomagnesemia:

• Deficiency may be due to diminished insulin action, insulin resistance related to reduced tyrosine kinase at the insulin receptor

• impaired insulin action due to impaired insulin signaling.

Side effects:¹

• GI upset, nausea, vomiting, diarrhea

• In diminished renal function, hypermagnesemia may occur

Drug interactions:^1,2

• Many medications may deplete magnesium levels: diuretics, proton pump inhibitors, digoxin, β-2 agonists, steroids, cyclosporine, tacrolimus, and others

• With magnesium supplementation: additive hypotension with calcium channel blockers or hypermagnesemia with potassium sparing diuretics (spironolactone)

• Concomitant magnesium administration may impair absorption of certain antibiotics, calcium, bisphosphonates

• Additive glucose-lowering effects with sulfonylureas and insulin

Milk thistle

Diabetes:

Possibly Effective

Hyperlipidemia,

• Diabetic

• Nephropathy,

• NAFLD,

• Nonalcoholic

• Steatohepatitis

• (NASH):

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,3,5,8

• Silymarin, a dry mixture of flavonolignans including:

  • – silybin A & B

  • – isosilibin A & B

  • – silychristine

  • – isosilychristine

  • – taxifolin

  • – silidianin

Various mechanisms^1-2,5,7-9,17

Diabetes

• Antioxidant, anti-inflammatory effects (helps with glucose reduction and prevents complications)

• Inhibits hepatic glucogenesis

• Decreased insulin resistance, possibly through cytoprotection

• Decreases malondialdehyde

• Peroxisome proliferator activated receptor-γ agonist

• Inhibits aldose reductase

Hyperlipidemia:

• Decreases cholesterol synthesis

• Decreases oxidized LDL

• May diminish HMG-Co-A reductase

• Diabetic Nephropathy

• May decrease interleukins, as well as TNF-α and TNF-β, a marker of fibrosis

Side effects:¹

• Diarrhea, weakness, sweating

• Possible allergic reactions if also allergic to ragweed, marigolds, daisies, chrysanthemums

• May have estrogenic effects, so women with breast or uterine cancer should avoid its use

Drug interactions:^1,11

• Phosphatidylcholine enhances bioavailability

• Beneficial interactions with hepatotoxic agents such as acetaminophen, antipsychotics, alcohol

• Increases concentrations of glucuronidated drugs (acetaminophen, haloperidol, lamotrigine)

• Increases absorption of chemotherapy drugs, calcium channel blockers, and some antibiotics

• May increase concentrations of raloxifene, tamoxifen

• May decrease concentration of antiretrovirals

• Additive glucose lowering effects with sulfonylureas and insulin

Mulberry

Diabetes:

Possibly Effective

Hyperlipidemia:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,3-4

• 1-deoxnojirimicin

• Fagomine

Various mechanisms^1,3-5

Diabetes:

• α-glucosidase inhibition

• Increased Insulin secretion

• May decrease insulin resistance by activating phosphatidylinositol-

• 3-kinase/protein kinase B, glycogen synthase kinase-3β signaling pathways

• Modulate glucose transporter-4 translocation

Hyperlipidemia

• Antioxidant affects may decrease lipid peroxidation (increased LDL resistance to oxidative changes)

Side effects:^1,6-7

• GI upset, including nausea, vomiting, abdominal fullness

• Headache

• Cough

• Increased serum creatinine

Drug interactions:¹

• Phosphatidylcholine enhances bioavailability

• Additive glucose-lowering effects with sulfonylureas and insulin

Nopal

Diabetes:

Possibly Effective

Hyperlipidemia,

Metabolic Syndrome,

Weight Loss, BPH,

Alcohol Hangover:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,3-4,6

• Fibrous polysaccharides

• Phytochemicals, such as pectin

• Phenolic compounds

• Flavonoids

• Betalains

• Chromium

Various mechanisms^1,3-4,6-7

Diabetes:

• Slows carbohydrate absorption

• Possibly increases insulin sensitivity

• Chromium content may improve glucose metabolism

Hyperlipidemia:

• Fiber content decreases lipid and fat absorption in the gut

Side effects:^1,5,11

• Diarrhea, nausea, abdominal fullness, increased stool volume

• Headache

• Hypoglycemia

Drug interactions:^1,11

• Additive glucose-lowering effects with sulfonylureas and insulin

Probiotics (Lactobacillus species and Others)

Diabetes,

Hyperlipidemia:

Possibly Effective

Obesity:

Insufficient Reliable

• Evidence to Rate

Numerous species, including:^1-5,25

• Lactobacillus species

• Bifidobacterium species

• Streptococcus thermophilus

• Saccharomyces boulardii

• Akkermansia muciniphila

• Clostridium species

• Anaerobutyricum hallii

Diabetes (theoretical):^1-5,25

• Possible enhanced incretin action

• Release of beneficial organic and free fatty acids that act against pathogenic microbes

• Decreased inflammation

• Decreased insulin resistance

• Antioxidant activity

Side effects:^2,9 :

• GI upset

• Constipation

• Possible systemic infections in immunocompromised or those on chemotherapy or radiation treatment.

Drug interactions:^1,14

• Antibiotics, antifungals: decreased probiotic effects

• Immunosuppressants (cyclosporine, methotrexate, etc): weakened state may lead to infections due to probiotic microbes

Psyllium

Diabetes,

Hypertension:

Possibly Effective

Hyperlipidemia:

Likely Effective

Obesity:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1-3

• Soluble viscous gel-forming fiber

• Mix of acidic and neutral polysaccharides with galacturonic acid

• Polysaccharides: D-xylose, L-arabinose, pentosanes

Various mechanisms^1-6

Diabetes:

• Formation of viscous gel that slows intestinal glucose absorption, thus lowering postprandial glucose

• Delayed gastric emptying

• Carbohydrate sequestering

• “Second meal effect”

Hyperlipidemia:

• Prevents reabsorption of bile salts and enhanced elimination in fecal bile acids

• Lowers dietary fat absorption

• Reduced cholesterol synthesis due to reduced insulin stimulation (due to lower glucose)

Obesity:

• May decrease appetite

Side effects:¹

• Allergies

• Cough

• Swallowing disorders

• Flatulence

• “Sugar-free” products may contain aspartame so persons with phenylketonuria may have issues

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

• Binding reactions: decreased absorption of many other drugs (anticonvulsants, metformin, iron, some psychiatric meds)

• Additive blood pressure or lipid lowering with antihypertensives and antihyperlipidemics

Tea

Diabetes,

Metabolic Syndrome,

NAFLD, Obesity:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia,

• Hypertension:

Possibly Effective

Various ingredients^1-3-5,8

• Green tea

  • – Epigallocatechin gallate (EGCG)

  • – Tannins

  • – Epigallocatechin

  • – Epicatechin

  • – Epicatechin gallate

  • – Gallocatechin gallate

  • – has more Catechins (polyphenols) than oolong and black tea

• Oolong and black tea

  • – Theaflavins

  • – Thearubigins

Various mechanisms^1,4-5,8-11

Diabetes:

• Inhibition of hepatic gluconeogenesis

• Enhanced insulin activity

• Decreased insulin resistance

• Tyrosine phosphorylation of insulin receptor and receptor substrate

• Suppresses phosphoenolpyruvate carboxykinase (gluconeogenic enzyme)

• Modulates glucose-6-phosphatase

• Improves cytokine-induced β-cell damage

• Regulates gene expression involved in insulin signal transduction pathways

• Antioxidant effects

• α-glucosidase and α-amylase inhibition.

Hyperlipidemia:

• Decreased LDL oxidation

• Enhanced gene expression of enzymes that stimulate bile acid production and decrease hepatic cholesterol concentration

• Upregulation of hepatic LDL receptors

• Hypertension:

• NADPH oxidase activity suppression

• Reduces reactive oxygen species

Obesity:

• Thermogenesis

• Decreased carbohydrate absorption

• Stimulate the sympathetic nervous system

• Appetite suppression

• Suppresses ghrelin

• Increases adiponectin

Side effects:^1,12

• Possible hepatoxicity

• GI upset

• Caffeine content may cause insomnia, anxiety, tachycardia

• Miscarriage if caffeine content is higher than 300 mg/day

Drug interactions:^1,8

• Sympathomimetics or amphetamines may cause toxicity due to caffeine content

• Increased blood pressure, heart rate with MAO inhibitors

• May antagonize antiplatelet effects of warfarin (Vit K content)

• Decreased concentrations of nadolol

• Negates calming effects of barbiturates

• Diminished absorption of iron and folic acid (may impact pregnant women)

• Additive glucose-lowering effects with sulfonylureas and insulin

Turmeric

Diabetes, Metabolic

• Syndrome, Obesity:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia,

• NAFLD:

Possibly Effective

Diabetic Nephropathy,

• Neuropathy,

• Retinopathy:

Not Rated by Natural

• Medicines

Various ingredients^1-3

• Curcumin

• Diferuloylmethane

• Demethoxycurcumin

• Bisdemethoxycurcumin

• Cyclocurcumin

Various mechanisms^1,4-6

Diabetes:

• Antioxidant

• Anti-inflammatory

• Improved β-cell function

• α-glucosidase inhibitor activity

• Inhibits TNF-α

• Inhibits NF-κB activation

• Lowers TBARS (thiobarbiturate acid reactive substance)

• PPARγ activation

• Activates hepatic enzymes involved with gluconeogenesis

• GLP-1 effects

• Microbiome modulation

Hyperlipidemia:

• Increased lipoprotein lipase

• Inhibits lipid peroxidation, protein carbonyl and lysosomal enzyme activities

• Decreases oxidized LDL levels

• Activates hepatic cholesterol α hydroxylase, stimulating conversion of cholesterol to bile acids

• Inhibits HMG CoA reductase

Obesity:

• Down regulates Janus kinase

Diabetic Nephropathy:

• Decreases renal inflammation by suppressing NF-κB and Ixβα action

• Decreases TGF beta-1 regulation, monocyte chemoattract protein-1, ICAM-1

Diabetic Neuropathy:

• Decreases neuroinflammatory lipid peroxidation

Diabetic Retinopathy:

• Stops retinal expression of proinflammatory cytokines, TNF-α,

Side effects:^1,9

• GI upset

• Pruritus, allergic dermatitis

• Root products have higher lead concentrations than curcuminoid extracts

• Antiplatelet properties

• May inhibit iron absorption

Drug interactions:^1,36,10

• Additive effects with antiplatelets/anticoagulants

• Inhibits CYP450 1A2, 2B6, 2C9, 2C19,

• 2D6, 2E1, 3A4, so may increase concentrations of several drugs: secretagogues, some statins, antihypertensives, warfarin, others

• May inhibit OAT-P and decrease clearance of meds that use these transporters (pioglitazone, repaglinide)

• Additive glucose-lowering effects with insulin or secretagogues

• Complexed with zinc or coadminsitered with piperidine to improve absorption and bioavailability

Vinegar

Diabetes, Obesity:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia:

Not Rated by Natural

• Medicines

Various ingredients^1,2

• Acetic acid

• Mineral salts

• Amino acids

• Polyphenols

  • – Galic acid

  • – Catechin

  • – Caffeic acid

  • – Ferulic acid

• Organic acids

  • – Tartaric

  • – Citric

  • – Malic

  • – Lactic

Various mechanisms^1,3-6

Diabetes:

• Delays gastric emptying

• Suppresses disaccharidases

• Promotes muscle glucose uptake

• Suppresses hepatic glucose production

• Increases peripheral tissue glucose utilization

• Enhances flow-mediated vasodilation

• Facilitates insulin secretion

• Binds to free fatty-acid receptors, which may increase GLP-1 secretion

• Stimulates 5’AMP-activated protein kinase (AMPK) activation

• GLUT-4 mobilization

Hyperlipidemia:

• AMPK activation

• Decreased sterol regulatory element binding protein-1

Obesity:

• Decrease visceral fat accumulation

• Decreased lipogenesis

• Increased lipolysis

• Increased oxygen consumption via AMPK activation

• Increased energy expenditure via PPAR-α gene

• Satiety due to increases in Peptide Y-Y and oxyntomodulin and decreased ghrelin

Side effects:^1,7-10

• GI upset

• Hypoglycemia in persons with gastroparesis

• Oropharyngeal inflammation; caustic esophageal injury

• Hypokalemia

Drug interactions:^1,10

• Hypokalemia with potassium depleters (diuretics or certain supplements) or digoxin toxicity (if hypokalemia occurs)

• Additive glucose-lowering effects with insulin or secretagogues

Zinc

Diabetes:

Possibly Effective

Various Salts¹

• Sulfate

• Gluconate

• Chloride

• Acetate

• Others

Various mechanisms^1-3

Diabetes:

• Antioxidant (decreases TBARS)

• Increases depleted antioxidant enzymes (glutathione peroxidase, super oxide dismutase, catalase)

• Increases glycolytic enzyme activity (phosphofructose and pyruvate kinase)

• Enhances phosphorylation reactions to activate insulin signaling cascade

• Mobilizes GLUT-4 transporters

• Protects β-cells by inhibiting activity of destructive amyloid polypeptides, proinflammatory molecules

• Zinc transporters have role in pancreatic islet cells and regulate insulin production

• α-glucosidase inhibition

• Due to antioxidant effects, helps decrease microvascular complications

Side effects:¹

• GI upset (nausea, vomiting)

• Metallic taste

• At higher doses, may cause copper deficiency and affect iron absorption

• At > 50 mg/day, may lower HDL

• Worsening prostate function

Drug interactions:¹

• Competes with chromium for absorption

• Iron and zinc may interfere with each other’s absorption

• High magnesium intake may decrease zinc absorption

• Taking with black coffee decreases zinc absorption

• May interfere with absorption of certain antibiotics: Ciprofloxacin, cephalexin, certain tetracyclines)

• Some medications may decrease zinc levels: Lisinopril, cholestyramine, steroids, some estrogens, proton pump inhibitors, some anticonvulsants: Phenytoin, divalproex sodium

α-Lipoic Acid

Diabetes, Diabetic

• Neuropathy,

• Hyperlipidemia,

• Obesity:

Possibly Effective

Diabetic Retinopathy,

Diabetic Nephropathy:

Possibly Ineffective

Various ingredients^1,3-7

• Dihydrolipoic acid (DHLA)

• R and S enantiomer

Various mechanisms^1-8

Diabetes:

• Promotes tyrosine phosphorylation of insulin receptor

• Promotes GLUT1 and GLUT4 activity to enhance glucose uptake

Diabetic Complications (Neuropathy, Retinopathy, Nephropathy):

• Antioxidant activity

• Catalytic agent associated with pyruvate dehydrogenase and

• α-ketoglutarate dehydrogenase enzyme complexes

• Interacts with pyrophosphatases to convert pyruvic acid to acetyl-coenzyme A (in the Krebs cycle) to produce energy in the form of ATP

• Augments/maintains glutathione (GSH)

• Increases levels of Nrf2

• Reactive oxygen species and reactive nitrogen species scavenger

• Helps regenerate endogenous Vit E and Vit C

Diabetic Complications (Neuropathy, Retinopathy, Nephropathy):

• Inhibits NF-κB activation

• Anti-inflammatory: decreases TNF-α, interleukin-6, and C-reactive protein

Obesity:

• Increases energy expenditure

• Suppresses hypothalamic AMP-

Side effects:¹

• Nausea, vomiting, vertigo

• Possible allergic skin reactions

• Malodorous urine

• Thyroid dysfunction

• IV: headache, pain, injection site reactions

Drug interactions:^1,2

• May attenuate benefit of chemotherapy

• Binds antacids if given at same time

• Food decreases bioavailability

• May decrease conversion of thyroxine to active T3 form

• Additive glucose-lowering effects with insulin and sulfonylureas

Benfotiamine

Diabetic Neuropathy:

Possibly Effective

Diabetic Nephropathy:

Possibly Ineffective

Peripheral

• Neuropathy:

“Possibly Ineffective”

Various ingredients^1,2

• Thiamine prodrug

Various mechanisms^1-4

Diabetic Complications (Neuropathy, Nephropathy, Retinopathy):

• Enhanced transketolase activity

  • – Inhibits diacylglycerol protein kinase C pathway

  • – Inhibits advanced glycation end product formation pathway

  • – Inhibits hexosamine pathway

• Inhibits activation of NK-κB

• Modulates Vascular Endothelial Growth Factor Receptor 2

• Activates Protein Kinase B to prevent hyperglycemia-induced apoptosis

• Anti-inflammatory: inhibits activation of Mitogen-Activated Protein Kinases (MAPK)

• Decreases Glycogen Synthase Kinase-3 β (modulates cell sur-vival)

Side effects:¹

• Possible skin rashes

Drug interactions:^1,2

• Drugs/plants that decrease thiamine activity

  • –Metformin

  • –Betel nut

• Plants that Cause Thiamine Deficiency

  • –Horsetail

• Drugs that decrease thiamine levels in body

  • –Antibiotics

  • –Oral contraceptives

  • –Diuretics

  • –Some anticonvulsants

  • –Chemotherapy drugs

Coenzyme Q10

>Congestive Heart

• Failure, Diabetic

• Neuropathy:

Possibly Effective

Diabetes:

Possibly Ineffective

Hypertension,

Hyperlipidemia,

• NAFLD,

Statin-Induced

• Myalgia,

Statin-Induced

• Myopathy:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,2

• Benzoquinone nucleus

• Polyisoprenoid tail (10 Units)

• Ubiquinone (fully oxidized) form

• Ubiquinol (reduced form)

Various mechanisms^1-7

Metabolic Functions:

• Co-factor in electron transport chain involved with ATP production

• Direct membrane stabilizer

• Antioxidant (free radical scavenger)

Diabetes:

• Increases activity of glycerol-3-phosphate dehydrogenase and thus improves glucose-stimulated insulin secretion

• Improved endothelial dysfunction

Heart failure:

• Helps with myocardial ATP production

• Overcoming reactive oxygen species

Hypertension:

• Vasodilation, which decreases peripheral resistance

Statin-Associated Muscle Symptoms:

• May correct mitochondrial dysfunction

Side effects:^1,8

• Abdominal upset

• Anorexia

• Dizziness

• Headache

Drug interactions:^1,8-13

• Warfarin – may see decreased INR

Drugs that decrease CoQ10:

• Statins

• Red yeast rice

• Omega-3 Fatty Acids

• Amitriptyline

• Antihypertensives

Disease states associated with lower CoQ10 levels:

• Heart failure (due to statin use)

• Diabetes

Beneficial CoQ10 Interactions:

• Doxoru bicin: CoQ10 diminishes cardiotoxicity (but also may diminish cancer benefits)

Fish Oil

High Triglycerides:

Effective

Heart Failure,

• Hypertension:

Possibly Effective

Diabetes, Prediabetes,

• NAFLD, Obesity,

• Diabetic

• Nephropathy,

Diabetic Retinopathy:

Likely Ineffective

Various ingredients^1,3

• EPA (Eicosapentanoic acid)

• DHA (Docosahexanoic acid)

Various mechanisms^1,3,4

Hypertriglyceridemia:

• Decreased lipogenesis and intestinal cholesterol absorption.

• Inhibits gene transcription for sterol regulatory element binding program

• Inhibits hepatic diacyl-glycerol acyl transferase

• PPAR-α modulation

• Increased triglyceride clearance by upregulating lipoprotein lipase

• Intracellular degradation of apolipoprotein B, thus interfering with VLDL secretion

Anti-inflammatory Effects:

• Decreases TNF-α

• Inhibits activation of NF-κB

• Inhibits different interleukins (IL-6 and IL-1β)

• Downregulates mitogen-activated protein kinases

• Decreases adhesion molecules (VCAM-1), E-selectin, others

• Modulate PPAR-α

Anti-thrombotic effects:

• Inhibits prothrombotic and vasoconstrictive mediator production (thromboxane A2 and thromboxane B2)

• Promotes thromboxane A3 production

Vasodilation:

• Promotes prostacyclin synthesis

Anti-arrhythmic Effects:

• Cardiac membrane stabilization by regulating calcium channels and intracellular calcium activity

Side effects:^1,3

• Gastrointestinal upset (loose stools, nausea, heartburn)

• Halitois

• Allergies

• Fishy taste

• Bleeding at doses > 3 g/day

Drug interactions:¹

• Warfarin; may see increased INR

• Additive effects with antihypertensives, hypoglycemics, anticoagulants, statins

• Decreases hypertensive effect of cyclosporine

Drugs that increase triglycerides: estrogens

Disease State Interactions (due to increased triglycerides:

• Pancreatitis

• Diabetes

Garcinia cambogia

Obesity:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,2

• Hydroxcycitric acid

Various mechanisms^1,2

Obesity:

• Inhibition of adenosine triphosphate citrate lyase, decreasing acetyl-CoA levels; leads to decreased fatty acid synthesis

• Decreased lipogenesis, which may decrease food intake

• Decreased conversion of Acetyl-CoA to malonyl-CoA

• Decreased hepatic glycogen synthesis and glucoreceptors (may help increase satiety)

• Increased brain serotonin reuptake activity

Side effects:^1-3

• GI upset

• Headache

• Pancreatitis

• Increased blood pressure

• Acute necrotizing eosinophilic myocarditis

• Affects platelet aggregation

• Hepatotoxicity (liver transplantation)

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

• Additive hepatotoxicity with hepatotoxins

• Serotonin syndrome in combination with SSRIs or other serotonergic drugs

Garlic

Hypertension,

• Hyperlipidemia,

• Diabetes:

Possibly Effective

Various ingredients^1,2

• Alliin

• Allicin

• Ajoene

• S-allyl-L-cysteine

• S-allylmercapto-cysteine

• Diallyldisulfide

• Dimethyltrisulfide

Various mechanisms^1-7

Hypertension:

• Nitric oxide, hydrogen sulfide production

• Decreased production of endothelin 1 and angiotensin II

Hyperlipidemia:

• Decreased activity of enzymes involved in cholesterol synthesis (glucose-6-phosphate-dehydrogenase)

• Decreased fatty acid synthetase (catalyzes fatty acid synthesis)

• HMG-Co-A reductase inhibition

• Suppressed LDL oxidation

Diabetes:

• Increased endogenous insulin production

• Increased insulin sensitivity

• Enhanced β-cell regeneration

• Inhibition of carbohydrate absorption

• Decreased oxidative stress

Side effects:¹

• Gastrointestinal (GI) discomfort

• Allergic reactions

• Burns (topical use)

• Bleeding

Drug interactions:¹

• Additive effects with antiplatelets/anticoagulants

• CYP3A4 inducer, thus lowering efficacy of protease inhibitors, some statins, certain anticonvulsants

• Decreases isoniazid levels 65%

• Increased ethanol, acetaminophen concentrations

• Additive hypotension with antihypertensives

• Additive glucose-lowering effects with sulfonylureas and insulin

Ginkgo biloba

Diabetic Retinopathy,

Glaucoma, Peripheral

• Arterial Disease:

Likely Ineffective

Diabetes:

Not Rated by Natural

• Medicines

Various Ingredients^1,2

• Flavone glycosides

  • –Quercetin

  • –Kaempferol

  • –Isorhamnetin

• Terpenoids

  • –Ginkgolides

  • –Bilobalides

Various mechanisms^1-3

• Diabetic Complications (Diabetic Retinopathy, Glaucoma, Peripheral Arterial Disease):

• Antioxidant activity

• Inhibits platelet aggregation

• Improves circulation

• Inhibits platelet-activating factor

• Increases ocular blood flow

Diabetes:

• May increase insulin secretion

Side effects:^1,4

• Gastrointestinal upset

• Headache

• Allergic reactions

• Seizures

• Bleeding

Drug interactions:^1,5

• Additive effects with antiplatelets/anticoagulants

• Hypomania (with melatonin, St John’s wort, some antidepressants)

• Increased serum drug concentrations

  • –Antipsychotics

  • –Antidepressants

  • –Cardiac medications

  • –Sulfonylureas

• Decreased serum drug concentrations

  • –Anticonvulsants (phenytoin)

  • –Some statins

  • –Cyclosporin

  • –Diltiazem

Glucomannan

Hyperlipidemia,

• Diabetes:

Possibly Effective

Hypertension, Obesity:

Insufficient Reliable

• Evidence to Rate

Various Ingredients^1,2

• Fiber

• Polysaccharide:

  • – D-glucose

  • – D-mannose (these are linked by β-1,4 glycosidic bonds)

Various mechanisms^1-5

Hyperlipidemia:

• Inhibits cholesterol absorption in jejunum

• Inhibits bile acid absorption in ileum

• Inhibits HMG-CoA-reductase

Diabetes:

• Increased viscosity and slowed food absorption in small intestine

• Decreased postprandial glucose: Blocks carbohydrate hydrolyzing enzymes

• Prebiotic effects

Obesity:

• Fecal energy loss

• Prolonged gastric emptying

• Satiety

• Increased chewing time

Side effects:^1,2

• Gastrointestinal upset

• Esophageal/intestinal obstruction

• Choking

Drug interactions:¹

• May bind other medications; do not administer at same time

• Binds vitamins A, D, E, K

• Additive glucose-lowering effects with sulfonylureas and insulin

• Additive lipid-lowering effects with antihyperlipidemics

Hibiscus

Hypertension:

Possibly Effective

Hyperlipidemia,

Obesity:

Insufficient

Reliable Evidence to

• Rate

Diabetes:

Not Rated by Natural

• Medicines

Various Ingredients^1-4

• Organic acids

  • – Malic

  • – Hibiscus

  • – Citrus

• Anthocyanins

  • – Delphinidin-3-sambubioside

  • – Cyanidin-3-sambubioside

• Polyphenols

• Flavonoids

  • – Gossypetine

  • – Hibiscetin

  • – Various glycosides

Various mechanisms^1-7

Hypertension:

• Angiotensin converting enzyme inhibition

• Diuresis

• Vasorelaxation

Hyperlipidemia:

• Inhibition of LDL-C oxidation

Obesity:

• Inhibits fat accumulation

• Decreases adipogenesis

Diabetes:

• α-glucosidase inhibition

Side effects:^1,8

• Gastrointestinal upset (abdominal distention, constipation)

• Dysuria

• Headache

• Tinnitus

• Hepatotoxicity

• Abortifacient properties

• May adversely affect fluid intake during lactation

Drug interactions:^1,10

• Decreased chloroquine efficacy

• Decreased simvastatin efficacy

• Additive glucose lowering effects with sulfonylureas and insulin

• Hypotension with antihypertensives

Pine Bark Extract

Chronic Venous

• Insufficiency:

Possibly Effective

Diabetic Retinopathy,

• Diabetes, Diabetic

• Foot Ulcers:

Insufficient Reliable

• Evidence to Rate

Hyperlipidemia:

Possibly Ineffective

Various ingredients^1-3

• Procyanidins (70+5%)

• Catechin

• Taxifolin

• Phenolic acids:

  • – Benzoic

  • – Cinnamic (includes gallic, caffeic, ferulic)

Various mechanisms^1,3

Chronic Venous Insufficiency, Diabetic

• Retinopathy, Diabetic Foot Ulcers:

  • Antioxidant

  • Anti-inflammatory

  • Enhances endothelial production of nitric oxide from L-arginine via nitric oxide synthase (enhances blood flow to retina, kidneys, peripheral circulation)

Hypertension:

• Enhanced endothelial function, vasodilation

• ACE inhibition

• Anti-thrombotic effect

Diabetes:

• α-glucosidase inhibition

Hyperlipidemia:

• Mitigates LDL oxidation

Side effects:^1,3

• Gastrointestinal upset

• Diarrhea

• Headache

• Rash

Drug interactions:¹

• Additive glucose-lowering effects with sulfonylureas and insulin

• Bleeding with antiplatelets or blood thinner

• Antagonizes immunosuppressants (steroids, cyclosporine)

Red Yeast Rice (RYR)

Hyperlipidemia:

Likely Effective

Various ingredients^1,3-4

• Unsaturated fatty acids

• Polyketides

• Phytosterols

• Pigments (rubropunctamine, monascorubramine)

• Monacolin M, L, J, X, K, others

Various mechanisms^1,3,5

Hyperlipidemia:

• HMG-CoA reductase inhibition

Side effects:^1,3,5

• Gastrointestinal upset

• Allergic reactions

• Myalgias

• Renal toxicity if citrinin inadvertently produced

• Teratogenicity

• Increased liver function tests

Drug interactions:^1,3

• Increased serum drug concentrations and possible toxicity of RYR: grapefruit, macrolides, azole antifungals, protease inhibitors, nefazodone

• Decreased serum drug concentrations and possible sub-therapeutic effect of RYR: St. John’s wort, some anticonvulsants

• Gemfibrozil: rhabdomyolysis

• Niacin: myopathy, liver toxicity

• Thyroid supplements: possible thyroid function abnormalities

St. John’s wort

Depression:

Likely Effective

Various ingredients¹

• Hyperforin

• Adhyperforin

• Hypericin

• Naphthodianthrones

• Flavonoids

Various mechanisms^1,2

Depression:

• Selective serotonin reuptake inhibition

• Prevents reuptake of norepinephrine and dopamine

• May affect GABA and glutamate

Side effects:^1,3

• Phototoxicity, photosensitivity

• Gastrointestinal upset

• Sleep difficulties

• Withdrawal symptoms if stopped abruptly

Drug interactions:^1,2

• Potent CYP 450 inducer of 3A4: Decreased cyclosporine, protease inhibitor, oral contraceptive, antihypertensive, statin, digoxin effectiveness

• Potent CYP 450 inducer of 2C9: Decreased warfarin effectiveness

• Additive serotonergic effects with other serotonergic drugs (serotonin syndrome possible)

• Possible increased sedation with narcotics and certain analgesics

Vitamin D

Osteoporosis:

Likely Effective

Diabetes:

Insufficient Reliable

• Evidence to Rate

Various ingredients^1,4

• Ergocalciferol (vitamin D2)

• Cholecalciferol (vitamin D3)

Various mechanisms^1-7

Osteoporosis:

• Regulates serum calcium and phosphorous concentrations

• Regulates bone health, muscle strength

• Anti-inflammatory: interferes with cytokine generation, action

Downregulates NF-κB

Diabetes:

• Low Vit D levels (once thought to be associated with impaired pancreatic β-cell function) and insulin resistance

Side effects:^1,8

• Toxicity when 25-OH(D) exceeds 150 ng/mL (374.4 nmol/L): Nausea, vomiting, poor appetite, weakness, weight loss, constipation

• Possible hypercalcemia with high doses

• Bone loss at high doses (4,000 to 10,000 IU/day of Vit D3)

Drug interactions:¹

• Decreased serum concentrations of vitamin D: Some anticonvulsants (phenobarbital, phenytoin), rifampin, some HIV medications

• Steroids: impair Vit D metabolism

• Impaired absorption of vitamin D: orlistat, cholestyramine

• Arrhythmias: with digoxin, if hypercalcemia

• Hypermagnesemia: with magnesium-containing antacids