Copyright By Pamela W. Smith, M.D., MPH, MS

Description

More than 80% of the population in the US who are adults have blood glucose levels that are too high.¹  If an individual has a fasting blood sugar (FBS) that is high-normal (over 85 mg/dL), the risk of the person dying of cardiovascular disease is increased by 40%.²  Furthermore, having a FBS high-normal (over 85 mg/dL) increases the patient’s risk of vascular death.³  Likewise, high-normal levels of FBS may account for a 6% to 10% decrease in the volume of the hippocampus and amygdala.⁴  Consequently, insulin resistance is a risk factor for cognitive decline. Also, the Honolulu-Asia Aging Study showed that the effect of hyperinsulinemia on the risk of dementia was independent of diabetes and blood glucose.^.5 Insulin resistance occurs when insulin is present but it does not work as effectively in the body as it should. Consequently, levels start to rise to help the body compensate for less than effective insulin function. Symptoms of insulin resistance include the following⁶: fuzzy brain, infertility, irregular menstrual cycles, irritability, loose bowel movements alternating with constipation, water retention, and weight gain.

The following are some of the common causes of insulin resistance:

• Genetic susceptibility,
• Eating processed foods,
• Increased stress,
• Excessive caffeine intake,
• Abuse of alcohol,
• Nicotine,
• Excessive dieting,
• Oral contraceptives,
• Lack of exercise,
• Decreased estrogen in women,
• Increased testosterone in men (over-dosage of testosterone replacement or due to elevated DHEA level),
• Increased testosterone in women (due to PCOS or elevated DHEA level),
• Decreased testosterone in men,
• Excessive progesterone in women (over-dosage that is prescribed),
• Insomnia,
• Elevated DHEA levels in men or women, and
• Hypothyroidism.

Conventional Therapies

Conventional therapies for insulin resistance are centered around exercise and a low glycemic index eating program. If the patient is overweight, then weight reduction is beneficial. If these methods are not successful, then a medication may be started such as metformin.

Personalized Medicine Therapies^7-10

Exercise is important. Lack of exercise is a risk factor for the development of insulin resistance and diabetes in susceptible individuals. A suggested exercise program is one hour, four times a week. If the patient has not been exercising and they are over the age of 40, then they should see their health care provider and have an ECG done before starting an exercise program.

A healthy diet is paramount to control insulin resistance starting with a low glycemic index (GI) eating program.¹¹ The GI ranks carbohydrates and carbohydrate-containing foods on a scale from 0 to 100 according to the speed with which they enter the bloodstream and raise glucose levels. Foods high on the list increase blood sugar and cause insulin to elevate. Also, high glycemic index foods increase the production of epinephrine and norepinephrine, which decrease insulin sensitivity.¹² A study showed that insulin secretion was lower in people who were on a low glycemic index program for only two weeks.¹³ Furthermore, the glycemic index is affected by the size of the particles into which the food breaks down. Therefore, the more processed the food or the longer it is cooked, the higher its glycemic index.

The best carbohydrates that curb insulin are broccoli, lentils, and chickpeas.¹⁴  Likewise, whole vs. refined grains have been shown to decrease the incidence of diabetes.^15-17  In addition, the fat content of a food has an effect on its glycemic index. The fat slows down the absorption and therefore lowers its glycemic index. Consequently, the right balance of saturated to polyunsaturated to monounsaturated fats is important both for the prevention and treatment of insulin resistance and diabetes.

Moreover, the optimal eating program to prevent and treat insulin resistance should be high in fiber. Low fiber intake has been shown in multiple studies to be a risk factor for the development of diabetes.^18-20  Specifically, soluble fiber has been shown to also lower insulin levels.^21-22  Getting enough protein in the diet is a key component for glycemic control. The protein content of the food also decreases the absorption of sugars and consequently decreases its glycemic load. If an individual is overweight, weight loss is very beneficial.

Good sleep hygiene is also important for overall health as well as glucose control. If a person does not sleep at least six and one-half hours a night and/or does not get restorative sleep, then insulin levels may rise and lead to insulin resistance.

Moreover, there are many nutritional supplements that help regulate blood sugar. The sooner they are started the better. Once the patient’s blood sugar is above 90 mg/dL, the patient is headed toward insulin resistance and eventual diabetes. Why wait? Start these personalized medicine therapies suggested above along with some of the following nutrients and/or botanical therapies. Bergamot, which is a polyphenol, is also extremely helpful for many individuals.

Nutritional supplements

• Chromium
  • Alpha lipoic acid
  • Magnesium
  • Vanadium
  • Vitamin D
  • EPA/DHA
  • Conjugated linoleic acid (CLA)
  • Biotin
  • Vitamin E
  • L-carnitine
  • L-carnosine
  • L-taurine
  • L-arginine

Botanical Supplements

• Berberine
  • Ginseng
  • Fenugreek
  • Bitter melon
  • Psyllium (fiber)
  • Aloe vera
  • Nopal
  • Gymnema sylvestre
  • Bilberry
  • Cinnamon
  • Green tea
  • Olive leaf extract (500 mg BID)
  • Green coffee bean extract
  • Pycnogenol
  • Ivy gourd
  • Clove extract
  • Maqui berry

Nutritional Supplements

Chromium is needed for carbohydrate and lipid metabolism. Elevated glucose, insulin, cholesterol, and triglycerides as well as decreased HDL can all be improved with chromium supplementation. It also increases insulin sensitivity by improving insulin binding to the cells by increasing the number of insulin receptors.^23,24 Dosage: 600 micrograms twice a day with normal kidney function.

Alpha lipoic acid (ALA) is both fat and water soluble and is a broad-spectrum antioxidant. ALA also functions as a co-enzyme in carbohydrate metabolism. It increases the number or activation of glucose transporters (GLUTs).²⁵ GLUTs are involved in regulating tissue-specific glucose uptake and metabolism in the liver, skeletal muscle, and adipose tissue to ensure homeostatic control of blood glucose levels. Reduced glucose transport activity results in poor use of energy substrates and is associated with insulin resistance and type 2 diabetes. Furthermore, alpha lipoic acid slows the development of diabetic neuropathy (nerve damage due to diabetes) and can be an effective therapy for diabetic neuropathy in conjunction with lowering blood sugar and other nutrients.²⁶ Dose: 300-400 mg a day.

Magnesium is involved in the activation of over 300 enzymes in the body. In addition, magnesium functions as an essential cofactor in glucose oxidation. It also modulates glucose transport across cell membranes. Magnesium deficiency is associated with insulin resistance.^27-29  Dose: 400-600 mg a day. Magnesium glycinate or magnesium threonate are particularly well absorbed forms of this mineral.

Vanadium has been shown to improve insulin sensitivity.^30-32 Dose: 10-50 micrograms a day. Exacerbation of bipolar disorder may be a side effect in higher doses. Consequently, 50 micrograms a day is the highest suggested dose.

Vitamin D is really a pro-hormone and not a vitamin. Low vitamin D levels are associated with insulin resistance and beta-cell dysfunction. One study revealed that metformin improves insulin sensitivity by 13% and a higher vitamin D status in the study correlated with a 60% improvement in insulin sensitivity.³³  In another trial, using 1,332 IU a day, for 30 days in 10 women with diabetes, vitamin D supplementation improved insulin sensitivity by 21%.³⁴

Omega-3-fatty acids, such as EPA/DHA, have a beneficial effect on plasma insulin and lipid concentrations in animals.³⁵  Furthermore, omega-3-fatty acids have many functions in the body with the most important being a fabulous anti-inflammatory agent. Dose: 2,000 mg daily.

Conjugated linoleic acid (CLA) is the only naturally occurring trans-fat. Animal studies have shown CLA to normalize impaired glucose tolerance and improve hyperinsulinemia. Dosage: 1,000 mg a day.^{36, 37}

Biotin deficiency results in an impairment of glucose utilization. A study in lab animals showed that biotin improved glucose handling without increasing insulin secretion.³⁸ The best way to improve biotin production by the body is for an individual to have a healthy gastrointestinal tract. Dose: 2-5 mg a day.

Vitamin E deficient individuals are more likely to develop type 2 diabetes. Likewise, vitamin E improves glucose tolerance and reduces glycosylation.^39-41

L-Carnitine is an amino acid that is an antioxidant. It influences free fatty acid and glucose oxidation. It may improve diabetic neuropathy.^42,43  Dosage: 1,000-2,000 mg a day with normal renal function. Intestinal bacteria produce the precursor of trimethylamine-N-oxide (TMAO), trimethylamine (TMA), from carnitine, choline, or choline-containing compounds. Therefore, measure TMAO levels before supplementing with L-carnitine. If TMAO levels are high, then carnitine and choline should not be taken.

L-Carnosine is a nutrient that is a combination of two amino acids, beta-alanine and histidine. It is an antioxidant, and it aids the body by preventing glycation.⁴⁴  Carnosine is found in the brain, skeletal muscles, heart, and the lens of the eye. Dosage: 1,000 mg a day with normal renal function.

L-Taurine is an amino acid. It requires zinc to help it function properly. Taurine has a positive effect on insulin sensitivity and helps to control blood glucose.^45-48 Stress depletes the body of taurine!  Dosage: 1,000-2,000 mg a day with normal renal function.

L-Arginine helps insulin sensitivity.⁴⁹  Use with caution in individuals with heart valves that are not functioning optimally. Dosage: 1,000 mg a day with normal renal function.

Botanical Supplements^50,51

Berberine (Berberis vulgaris) has been shown to help lower blood sugar. It also may regulate insulin receptor transcription.⁵²  Dose: 200-500 mg two to three times a day. This botanical can cause uterine contractions; therefore, it is not to be used in pregnancy. The most common possible side effect is GI upset.

Ginseng species contains triterpenoid glycosides that lower blood sugar by regulating hepatic glucose uptake, glycogen synthesis, and insulin release. Ginseng (Panax quinquefolius—American ginseng) has been shown to reduce post-prandial glycemia in both type 2 diabetics and non-diabetics.⁵³  In an eight-week trial, it decreased fasting blood glucose and HgA1C.⁵⁴ Dose: Panax ginseng: 100-400 mg of extract standardized to 4% ginsenosides.⁵⁵ 

Fenugreek seed (Trigonella foenum graecum) has a hypoglycemic effect due to its high soluble fiber content, which decreases the rate of gastric emptying and delays the absorption of glucose from the small intestine.^56-59 It also lowers cholesterol and triglycerides. There may be a cross-reaction if an individual is allergic to chickpeas.⁶⁰  Possible side effects include diarrhea, flatulence, and dizziness.^61-63  Furthermore, fenugreek preparations can contain coumarin derivatives and consequently could increase bleeding in a person with a blood dyscrasia or someone that is taking a blood thinning medication.⁶⁴  Since fenugreek is high in fiber, minerals and medications should be taken separately from fenugreek-containing products. Likewise, in one study, fenugreek lowered potassium in a small group of people. Therefore, fenugreek may precipitate hypokalemia (low potassium levels) when used in combination with some laxatives or medications that lower potassium.⁶⁵ Also, decreases in the serum level of T3 and in the T3/T4 ratio, as well as an increase in the level of T4 have occurred in animals give fenugreek. Therefore, thyroid studies are suggested for individuals taking fenugreek.⁶⁶

Bitter melon (Momordica charantia) is a tropical fruit widely used in Asia, Africa, and South America. It is also called bitter gourd. The precise mechanism of action is unknown. Hypothesized actions include the following: increased insulin secretion, increased glucose oxidation, and decreased hepatic gluconeogenesis.^67-70  Active components of bitter melon are charantin, vicine, and polypeptide-p (an insulin-like protein). Interestingly, a study on charantin found it to be a more potent hypoglycemic agent than tolbutamide. 

Aloe vera in a single-blind, placebo-controlled trial of diabetics over two weeks showed improved blood sugar control.⁷¹

Nopal (Optunia streptacantha) is also called prickly pear cactus. It is high in fiber and pectin. Studies have shown its hypoglycemic (blood sugar lowering) effect.^72,73

Gymnema sylvestre is an herb endemic to India. The common name is gurmar, which means “sugar-destroying.” It has been shown in clinical trials to lower blood sugar.^74-76

Cinnamon, cloves, bay leaves all have insulin-like or insulin-potentiating action in vitro.^77,78 Therefore, spicing up your life can help control/improve insulin resistance. Possible side effects of cinnamon include the following: GI upset, stomatitis, and perioral dermatitis.

Green tea in a study revealed that it contains insulin-enhancing activity through its predominant active ingredient of epigallocatechin gallate (EGCG).⁷⁹  EGCG was also shown to be a possible therapeutic agent for the prevention of diabetes mellitus progression. Another study showed that EGCG protected cytokine-induced B-cell damage, which is partly mediated by suppression of inducible nitric oxide synthase (iNOS) activity.⁸⁰

Olive leaf extract contain oleuropein, which has been shown to lower blood sugar. It slows the digestion of starches into simple sugars and slows the absorption of simple sugars from the intestine. Furthermore, it Increases the uptake of glucose into tissues from the blood and lowers fasting insulin levels.^81-83 In animal trials, diabetic rats were given olive leaf extract. They had a significant reduction in their blood sugar and cholesterol.^84-85 In human trials, a study using 500 mg of olive leaf extract a day significantly lowered HGBA1C.⁸⁶  Another human trial revealed that olive leaf extract improved insulin sensitivity significantly in overweight middle-aged men.⁸⁷

Green coffee bean extract has been shown to work like metformin in lowering blood sugar. It lowers after-meal glucose surges. One study showed that green coffee bean extract that was standardized reduced after-meal glucose by about one-third.⁸⁸

Pycnogenol (Pinus maritima) is a standardized extract of French maritime pine bark. A study conducted on type II diabetics who were given 125 mg of Pycnogenol a day vs. placebo: individuals in the treatment group had lower HgBA1C, lower blood pressure, and lower LDL than before the study began.⁸⁹

Ivy gourd (Coccinia indica) is an herb in the cucumber family. It helps insulin by its effects on lipoprotein lipase, glucose-6-phosphatase, and other glycolytic enzymes.⁹⁰  Two studies have shown that ivy gourd had significant glucose-lowering effects.^91-92  Dose: dried leaves or extracts at doses equivalent to 15 grams daily with meals. Ivy gourd has no known side effects.

Clove extract in a medical trial significantly lowered after-meal blood sugar levels. Dose: 250 mg before a meal with the most starches or sugars.⁹³

Maqui berry extract has been shown to lower postprandial blood sugar and insulin. It also showed promise to lower HgA1C.^94,95

Polyphenol: Bergamot

Bergamot juice is a polyphenol. There are a variety of phytochemicals that have been found in bergamot, including brutieridin and melitidin as well as other flavonoids and  flavones O-glucosides and C-glucosides. Bergamot has several main modes of action. Bergamot works directly on the insulin receptor, thus effectively lowering blood sugar.⁹⁶ In addition, bergamot blocks cholesterol absorption in the gut, like the plant sterols found in avocado, which is the major reason it is important to take bergamot before meals, i.e., to block the absorption of cholesterol and other fats following the ingestion of a meal.⁹⁷ Consequently, bergamot lowers total cholesterol, LDL cholesterol, and triglycerides. It also has been shown to raise HDL.^98,99 This polyphenol also works to block the rate-limiting step in cholesterol production known as the HMG CoA reductase enzyme, which is the enzyme that is blocked by statin drugs. However, bergamot works at a different site on this enzyme, and therefore it does not appear to affect muscles and the liver in the same way that statin drugs may. In addition, bergamot has anti-inflammatory action and is an antioxidant.  100 Dose: 800 mg twice a day.

Conclusion

As you have seen, it is important to treat insulin resistance early in the course of the disease. A conventional and personalized medicine approach to insulin resistance has a lot to offer so that every patient, hopefully, will be able to control insulin production and prevent type 2 diabetes.

CLICK HERE FOR REFERENCES