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Substance
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Mechanism of Action
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Safety
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Efficacy in Diabetes
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Dose
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Cassia Cinnamon1
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Increases phosphorylation of insulin receptor, improving insulin sensitivity. Has also been shown to stimulate insulin release, but human studies are conflicting.
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-Generally Recognized as Safe (GRAS) when used orally at appropriate doses up to 4 months.
-Possibly Unsafe when used in high doses long-term (50-7,000 mg/day) due to hepatotoxicity. Avoid in liver disease.
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-Possibly Effective: data is conflicting but meta-analysis of 120 mg-6g daily for 4-18 weeks reduced FBG by an average of 25 mg/dl and also slightly improved lipid panels. Less evidence in reducing A1c due to length of studies.
-Of note Ceylon Cinnamon is possibly ineffective
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120 mg to 6 g per day for up to 4 months
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Berberine2
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Human studies: Increases insulin receptor expression in peripheral blood lymphocytes
Animal and in-vitro studies:
-Increases AMPK activity (similar to metformin).
-Increases GLP-1 secretion.
-Increases PPAR-a (similar to pioglitazone) and PPAR-d expression
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-Possibly Safe when used orally at doses up to 2g/day for 8 weeks
-Likely Unsafe in newborns, pregnancy, and lactation due to risk of kernicterus
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-Possibly Effective: An analysis of clinical evidence that use in combination with lifestyle reduces FBG by 15 mg/dl, PPBG by 34 mg/dl, and A1c by 0.71% vs. lifestyle alone. In combination with other diabetes medications it has shown to lower A1c by 0.58% vs. other diabetes medications alone. May also lower cholesterol.
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0.9-1.5 grams, taken in two to three divided doses daily, has been used for 2-4 months
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Chromium3
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-People with diabetes may have lower chromium levels which is associated with impaired glucose, insulin, lipid metabolism and increased CVD risk.
-Supplementation may increase insulin receptors and affinity.
-Has been shown to increase sensitivity and stimulate insulin receptors in patients with type 2 diabetes.
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-Likely Safe at appropriate amounts short term. FDA recommends not to exceed 200 mcg daily for 6 months, but has been studied at higher doses.
-Possibly Safe at higher doses and longer duration such as 200-1,000 mcg daily for up to 2 years, but not recommended
-Likely Safe in children, pregnancy and lactation
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-Possibly Effective: an analysis of 10-18 clinical studies show that it can decrease A1c by up to 0.6% and FBG by 18 mg/dl. Some speculation that since studies were done in countries where poor nutritional status is more likely may not apply to US population.
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200 mcg daily in single or divided doses for 6 months is most safe
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Apple Cider Vinegar4
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May delay gastric emptying and prevent carbohydrate breakdown (similar to acarbose).
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-Likely Safe when used orally and in appropriate food amounts
-Possibly Safe when used for medicinal purposes for up to 12 weeks
-Of note it has been shown to worsen gastroparesis in type 1 diabetes patients
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- Insufficient Reliable Evidence To Rate: preliminary clinical research of 20g with a meal improved post-prandial insulin sensitivity and reduced insulin level fluctuations in those with insulin resistance, but not in type 2 diabetes
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20g with meals for up to 12 weeks
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Bitter Melon5
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-May decrease hepatic gluconeogenesis, increase hepatic glycogen synthesis, increase insulin secretion, and increase glucose oxidation in erythrocytes and adipocytes
-May increase muscle content of GLUT-4
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-Possibly Safe: when used orally and appropriately short term. Powdered formulation 2-4g daily for 10 weeks has been used. Extracts have been used for 3 months.
-Possibly Unsafe in pregnancy due to abortifacient properties seen in animals
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- Insufficient Reliable Evidence To Rate: conflicting clinical studies with some showing benefit in lowering A1c similar to a sulfonylurea and others showing no benefit vs. placebo.
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Powdered bitter melon 2-4g daily for 10 weeks has been used
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Aloe6
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-Human research is inconclusive, but stimulates insulin release from beta cells in mice with diabetes
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-Possibly Safe when aloe gel used orally and short-term
-Possibly unsafe when used in children, pregnancy and lactation
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Possibly Effective: most clinical research shows it can reduce FBG 30-47 mg/dl and A1c by 0.41% to 1.05% in those with prediabetes and diabetes. However, contradictory studies exist which show no effect vs. placebo. May be due to variety of preparations used.
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Most effective dose and formulation is unknown.
-Solid formulations: 100-1000 mg daily
-Juice: 15-150 mL daily
-Gel: 15 mL daily for up to 4 weeks
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Alpha-Lipoic-Acid7
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-Humans: improves insulin sensitivity
-Animals: prevents diabetic endothelial damage, reduced albuminuria as an antioxidant, activates AMPK
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-Possibly Safe when used at the appropriate dose from 3 months to 4 years.
-Possibly Unsafe in children in large amounts (toxicity)
-Possibly Safe in pregnancy short-term (600 mg for up to 4 weeks). Avoid in lactation.
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Possibly Effective: Most studies show 300-1800 mg daily by mouth for 4-8 weeks or IV 1-10 days improves FBG and PPBG but conflicting evidence shows no effect vs. placebo
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Thioctacid (Asta Medica) 300-1800 mg daily for 4-8 weeks
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American Ginseng8
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-Thought to reduce PPBG due to improved insulin sensitivity or stimulation of insulin release. American ginseng appears to be more effective vs. Panax ginseng
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-Likely Safe when used short-term (100-3000 mg daily for up to 12 weeks). An extract called CVT-E002 (Cold-FX, Afexa Life Sciences, Canada) has been used safely for 64 months
-Possibly Safe in children when used short-term
-Possibly Unsafe in pregnancy (teratogenic in animals)
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Possibly Effective: 3g by mouth up to 2 hours before a meal can reduce PPBG but doses >3g do not offer additional benefit. Taking 100-200 mg daily for 8 weeks can reduce fasting blood sugar.
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3g up to 2 hours before a meal to avoid hypoglycemia. 100-200 mg daily for 8 weeks for FBG
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Fenugreek9
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-Likely related to fiber and amino acids. Seeds contain 50% dietary fiber and pectin, slows gastric emptying and absorption. 80% of free amino acids is present as 4-hydroxyisoleucine which may cause glucose-dependent insulin secretion.
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-Likely Safe (GRAS in the US): in food amounts
- Possibly Safe: when used in medicinal amounts for up to 6 months
-Possibly Unsafe: in children
-Likely Unsafe: in pregnancy (malformations)
-Possibly Safe: in lactation
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Possibly Effective: lowers FBG by 15 mg/dl; also lowers PPBG and A1c in type 2 diabetes. In type 1 diabetes taking 50g of defatted fenugreek seed powder BID with meals for 10 days reduced 24-hour urine glucose levels by 54%
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-Powdered fenugreek seed: 5-100g/day with 1-2 meals per day for 4 days to 3 years
-Extract of fenugreek seeds: 1g/day for 2 months
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Garlic10
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Lowers BG in people with or without diabetes. In-vitro evidence shows S-allyl cysteine sulfoxide stimulates insulin secretion. Another In-vitro study showed aged garlic extract inhibits formation of advanced glycation end-products (protecting from complications)
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-Likely Safe: has been used in clinical studies lasting 7 years without reports of toxicity
-Possibly Safe: in children short term (300 mg TID x 8 weeks)
-Likely Safe: in pregnancy when used in food amounts
-Possibly Unsafe: in medicinal amounts in lactation
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Possibly Effective: analysis from 7 clinical trials showed that garlic powder 600-1500 mg daily, garlic oil 8.2 mg daily, or aged garlic extract 1000 mg daily reduces FBG by 30 mg/dl vs. control patients with type 2 diabetes. Garlic powder is most effective. In combination with metformin at 300 mg TID, garlic reduced FBG 70% more than metformin alone (used for 24 weeks). Not enough data for PPBG or A1c.
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-Garlic powder 600-1500 mg daily in divided doses for at least 12 weeks
-Specific products (Allicor, INAT-Farma or Kwai, Lichtwer Pharma): 300 mg 2-3 times daily in combination with metformin or sulonfonylrea for 4-24 weeks has been studied
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Magnesium11
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-Low magnesium is associated with increased risk of metabolic syndrome.
-Uncontrolled diabetes can increase urinary loss of magnesium
-Low intracellular magnesium disrupts tyrosine kinase activity at the insulin receptor causing insulin resistance
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-Likely Safe: when used in doses < 350 mg/day
-Possibly Unsafe: when use >350 mg/day (diarrhea)
-Likely Safe: in children at appropriate doses
-Likely Safe: in pregnancy and lactation at <350 mg/day
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Possibly Effective: Hypomagnesemia occurs in 25-38% of diabetes patients and is more common in poorly controlled diabetes. Lower levels associated with more rapid decline in renal function. Use of supplements have shown mixed results. Some studies have found decreased FBGs and improved insulin sensitivity with others showing no effect.
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-Magnesium chloride: 2.5g in 50mL solution daily for 16 weeks
-250 mg of elemental magnesium (as oxide, gluconate, lactate) daily for 3 months
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Milk Thistle12
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-Animals: decreases insulin resistance and protects pancreas due to antioxidant effects
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-Likely Safe: milk thistle extract containing 70-80% silymarin (Legalon, Madaus GmbH) has been used up to 420 mg daily for up to 4 years. Higher doses of 2100 mg daily has been safely used for 48 weeks. Other formulations and doses have also been found to be safe.
-Pregnancy & Lactation: insufficient information
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Possibly Effective: extract of silymarin 140 mg TID for 45 days reduces FBG by 11%, reduces insulin by 14%, improves insulin resistance by 26% vs. baseline and vs. placebo in patients with type 2 diabetes. Also improvements in HDL. Other clinical research shows silymarin 200 mg 1 or 3 times daily for 4 months in combination with conventional treatment lowers FBG by 23-43 mg/dl and A1c by 1% to 1.5% vs. baseline.
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-Livergol (Goldaru Herbal Products Pharmaceutical Company) 140 mg TID x 45 days
-Silymarin 200 mg once to three times daily for 4 months to 1 year
-Berberol (PharmExtracta): milk thistle extract 210 mg and tree turmeric extract 1176 mg daily x 3-12 months
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Olive13
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-Humans: improved insulin response effects of olive leaf extract due to improvements in beta cell function and reduction in inflammatory mediators
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-Likely Safe: when olive oil used as 14% of daily calories or 2 Tbsp (28g) daily
-Possibly Safe: when olive leaf extract used for up to 12 months
-Pregnancy & Lactation: avoid due to insufficient information
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Possibly Effective: olive oil intake for 2 weeks to 4 years reduces A1c by 0.3% and FBG by 6 mg/dl vs. control patients with type 2 diabetes. Olive oil in a Mediterranean-type diet reduces chylomicron remnant particles vs. polyunsaturated diet. Olive oil may be a better choice vs. sunflower oil.
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-15-20g daily has been associated with reduced diabetes risk. Doses higher than 20g/day confers no additional benefit
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