By Dr. Harry G. Preuss MD

Dietary supplements to prevent and/or ameliorate many chronic disorders of aging and perhaps aging itself: Focus on insulin resistance.

Insulin resistance (IR) is being placed under an increasingly bright spotlight in the medical community.  More and more health disorder are being linked to it1. Despite knowledge of potential harm, the number of individuals diagnosed with type 2 diabetes, a severe form of IR, is progressing alarmingly to the point that even the general public is now aware of the current worsening diabetes epidemic.  In our previous reports, we have hammered on the principle that over time IR in humans generally increases with “normal aging,” even though fasting blood glucose (FBG) levels, a surrogate for IR often remain in a range still considered normal by most medical practitioners2-5. In addition, it would appear that a greater number of non-diabetics are in that higher level of the accepted normal range for IR based on a parallel escalating incidence of type 2 diabetes.  

What’ the remedy?  The best means to diminish IR and it adverse associations is via an optimal dietary regimen, e.g., lessening intake of calories and rapidly absorbed carbohydrates and increasing soluble fiber consumption.  A reasonable corresponding exercise program is also beneficial. All this has the potential to ameliorate IR. Although many people on the verge of developing diabetes may realize this, nevertheless, too few actually have the will power to comply with the necessary natural requirements alone over a lifetime.  Something is lacking!

Drugs have been implemented along with lifestyle changes in various research protocols designed to prevent IR and type 2 diabetes.  While inclusion of drugs in the various regimens appears to have some added merit, by and large, their removal eventually causes abrupt loss of some prior positive gains.  Even more disturbing, the major fear leading to avoidance of prolonged drug use is their potential for adverse reactions. Most attempts to develop a wonder drug to prevent or treat diabetes have resulted in associated complications, particularly cardiovascular maladies.  Unfortunately, many drugs work through increasing insulin concentrations and excess circulating insulin over time is known to cause harm especially to the vasculature. Suffice it to say, there is sensible reluctance to use drug therapy over long term to prevent or lessen manifestations of IR and type 2 diabetes, because the consequence from the treatment may even be worse than doing nothing.

In contrast to drugs, natural dietary substances with a long history of safety have not been employed extensively in major clinical studies despite their potential to overcome IR, promote weight loss, lower elevated blood pressure, and/or produce a more healthful lipid profile.  As a general rule, natural dietary supplements compared to drugs while less potent also cause fewer adverse reactions. However, there is less availability of adequate clinical information on natural supplements to favorably influence IR. The major reasons behind the paucity of cogent clinical research performed on natural dietary supplements compared to drugs are simple. The typical manufacturer of natural agents compared to manufacturers of pharmaceuticals has meager a cash supply available to sponsor definitive research.  In addition, difficulties in patenting natural substances play a negative role in the development process.

Major anti-diabetic drugs can be classified as insulin stimulators that increase production and/or release of insulin (sulfonylureas, and meglitinides), compounds that block the gastrointestinal absorption of CHO (acarbose, voglibose), remedies that reduce hepatic glucose production (biguanides), and preparations that improve insulin action peripherally (thiazolidinediones and biguanides).  In many instances, the natural dietary supplements that have a beneficial effect on glucose-insulin metabolism do so via multiple somewhat similar mechanisms. For instance, both the (–)-hydroxycitric acid in Garcinia cambogia and the chlorogenic acids in green coffee bean extract can control to varying degrees CHO digestion and absorption, liver gluconeogenesis, and insulin sensitivity as well as other mechanisms.  Despite all difficulties, an attempt will be made to compare the workings of natural dietary supplements with drugs used to treat IR/Type 2 diabetes. 

As a first approximation, attempts to classify natural supplements in the same manner as drugs might look like this: compounds that augment insulin production and/or release (Gymnema sylvestre, fenugreek, garlic), ingredients that beneficially decrease and delay gut absorption of CHO (soluble fibers and carb blockers like bean extract and l-arabinose), substances that reduce hepatic glucose production (biotin), and items that improve insulin action peripherally (trivalent chromium, cinnamon, maitake mushroom SX fraction, and bitter melon).

We will begin to highlight a few of the most popular natural supplements that have the potential to optimize the glucose-insulin system in the next report.


  1. DeFronzo RA, Ferinimmi E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14:173-194, 1991.
  2. Preuss HG: The insulin system in health and disease (Editorial). J Am Coll Nutr 16:393-394, 1997.
  3. Preuss HG: Effects of glucose/insulin perturbations on aging and chronic disorders of aging: the evidence. J Am Coll Nutr 16:397-403, 1997.
  4. Preuss HG, Mrvichin N, Bagchi D, Preuss J, Perricone N, Kaats GR: Importance of fasting blood glucose in screening/tracking over-all health. The Original Internist 23:13-20, 2016.
  5. Preuss HG, Mrvichin N, Bagchi D, Preuss J, Perricone N, Kaats GR: Fasting circulating glucose levels in the non-diabetic range correlate appropriately with many components of the metabolic syndrome. The Original Internist 23:78-89, 2016.

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