Blood Sugar and Botanicals

With an estimated 35% of U.S. adults over the age of 20 with prediabetes, and an additional 26 million with full-blown diabetes (according to NIH statistics), impaired blood sugar control is a rampant issue. Prediabetes is defined as having fasting plasma sugar levels of between 100 and 125 mg/dl, while a diagnosis of diabetes requires a fasting plasma sugar level of greater than 126 mg/dl. Without significant lifestyle modifications, most individuals with prediabetes progress to diabetes within 10 years.

A major contributing factor to impaired blood sugar control is insulin resistance, wherein the body’s production of the hormone insulin is initially normal, but its ability to use insulin effectively is decreased. In this state, muscle, fat, and liver cells do not respond properly to insulin because of defective insulin receptor function, and glucose is unable to efficiently enter cells. As a result, sugar levels build up in the bloodstream. To compensate, the pancreas produces more insulin, and, over time, this process becomes overburdened, and the pancreas can’t keep up with the increasing need for insulin. This complication leads to prediabetes and diabetes.

Causes and Effects of Insulin Resistance

Insulin is essential for regulating carbohydrate and fat metabolism in the human body. It normally stimulates the uptake of glucose from the bloodstream into muscle, fat, and liver cells. Outside of these tissues, evidence points to critical roles of insulin in the brain, including neuroprotective effects, enhancement of synaptic plasticity (the ability of nerve synapses to compensate for changes in activity levels over time), neuron survival regulation, and insulin’s ability to act as a growth factor (The Journal of Clinical Investigation, 2013). Insulin resistance occurs as a result of many factors. Primary among them are obesity and excess weight, excessive caloric intake, lack of physical activity, genetic factors, and the aging process (Arteriosclerosis, Thrombosis, and Vascular Biology, 2012).

While a direct outcome of prolonged insulin resistance is dysregulated blood sugar, insulin resistance is associated with several serious medical conditions including type 2 diabetes, metabolic syndrome, atherosclerosis, and high blood pressure. Two areas of high research interest include the impact of insulin resistance on heart and brain health.

In a recent review, E. Dale Abel and colleagues from the University of Utah School of Medicine and New York University explored the molecular mechanisms implicating insulin resistance with increased risk of cardiovascular disease (Arteriosclerosis, Thrombosis, and Vascular Biology, 2012). Heart tissue has a constant requirement for energy to meet its significant functional demands, and it uses a combination of available glucose and free fatty acids to support energy metabolism. Insulin resistance impairs the heart’s ability to adjust to ever-changing energy demands by reducing its use of glucose as fuel, shifting this crucial fuel balance towards a greater reliance on fatty acids for energy production. While the heart adapts, this comes at significant long-term cost. A greater reliance on fatty acids for fuel leads to increased cellular stress in the forms of increased free radical production, defects in mitochondrial function, and apoptosis (programmed cell death) of heart cells. These changes occur as a result of insulin resistance, and they can contribute to adverse structural and functional changes in heart tissue and predispose the heart to cardiomyopathy and heart failure.

The interplay between insulin resistance and brain health is just as critical. In a 2013 review paper, Fernanda De Felice from the Federal University of Rio De Janeiro in Brazil explores the evidence linking defective brain insulin signaling to the development of Alzheimer’s disease (The Journal of Clinical Investigation, 2013). Because of the common feature of insulin resistance, diabetes and Alzheimer’s disease share similar inflammatory signaling pathways.

Research has also confirmed that insulin receptors are widely distributed throughout brain tissue. The hippocampus, an area of the brain fundamentally involved with memory function, has a particularly high concentration of these receptors. While the role of insulin and receptors in brain function is still an emerging area of research, clinical evidence points to important associations between type 2 diabetes and neurological disorders, including stroke, Alzheimer’s, dementia, and Parkinson disease. Some studies have shown that type 2 diabetics may be twice as likely to develop Alzheimer’s as non-diabetics. Further, several known biomarkers of insulin resistance are greatly increased in the hippocampus of non-diabetic individuals with Alzheimer’s disease, indicating that defective brain insulin signaling is an important feature of this pathology.

To reinforce this line of thinking, Paul Crane, MD, and colleagues from the University of Washington explored the link between glucose levels and risk of dementia (The New England Journal of Medicine, 2013). In a study involving 2067 participants with a mean age of 76 years at baseline, Crane and colleagues found that, during a median follow-up of 6.8 years, 524 participants developed dementia. In both diabetics and non-diabetics, higher average blood glucose levels during the previous five years were related to an increased risk for dementia.

It’s clear that insulin resistance is a significant contributor to chronic disease risk, but addressing blood sugar and insulin levels through early detection and supplementation may mitigate the risk of adverse health conditions. A number of herbal extracts have been shown to address insulin resistance, blood sugar metabolism, and related health parameters.

Berberine

Berberine, an alkaloid found in many plants, has a long history of use in traditional Chinese medicine. For instance, the herb Coptis chinensis, or Chinese goldthread, has a documented history of use as an antidiabetic dating back 1500 years. And Chinese goldthread’s major constituent is berberine (Evidence-Based Complementary and Alternative Medicine, 2011).

Animal studies have confirmed berberine’s benefits on blood sugar control while also highlighting berberine’s significant impact on cardiovascular health. In one such study, transgenic mice on a high-fat diet and exhibiting severe obesity, high blood sugar and insulin levels, and glucose intolerance were administered 250 mg of berberine/kg of body weight for four weeks (Evidence-Based Complementary and Alternative Medicine, 2011). Compared to a control group, mice in the berberine group exhibited decreased fasting blood glucose levels, lower fasting plasma insulin levels, better insulin sensitivity, and enhanced glucose tolerance. Berberine also improved total cholesterol and triglyceride levels in these animals.

When the authors explored berberine’s mechanism of action, they found that the compound had a multi-faceted effect on regulating genes involved in glucose transport and genes involved in the the metabolism of glucose, cholesterol, and fatty acids.

Studies on rats point to another beneficial aspect of berberine in diabetes. Administration of berberine to experimentally-diabetic rats was again found to lower fasting blood glucose, cholesterol, and triglycerides-in a manner equivalent to the antidiabetic drug metformin-but it was further shown to exhibit a renal protective effect (Phytomedicine, 2012). The authors of the study postulated that the renal-protective effect was due to berberine’s antioxidant activity and an inhibitory effect on glycosylation. Glycosylation is the binding of sugar molecules with circulating protein and fat molecules-a process that is potentially damaging to several tissues, including the kidneys.

Several human studies attest to berberine’s potential for lowering blood sugar. For example, Hao Zhang and colleagues from the Chinese Academy of Medical Sciences in Beijing conducted a clinical trial in which 97 patients with type 2 diabetes were administered berberine (1000 mg/day), metformin (1500 mg/day), or rosiglitazone (4 mg/day) for two months (Metabolism Clinical and Experimental, 2010). Fasting blood sugar levels and hemoglobin A1c (HbA1c) fell significantly in all three groups, while berberine also significantly reduced triglyceride levels. With berberine, fasting blood glucose values were reduced on average from 187 mg/dl to 139 mg/dl; HbA1c levels decreased from 8.3% at the beginning of the study to 6.8% at the end; and triglyceride values changed from an average of 150 mg/dl to 104 mg/dl. These studies indicate that berberine is a potentially potent herbal compound with antidiabetic effects.

Jambul

The fruit of an evergreen tree that grows throughout the Indian subcontinent, black plum (jambul or jamun in Hindi; Syzygium cumini) is commonly used in traditional medicine to address diabetes. Jambul fruits and seeds possess phenolic and flavonoid compounds with hypoglycemic activity. As reviewed in a recently published paper by Shalini Srivastava and Deepak Chandra of the University of Lucknow in India, several animal studies have shown antidiabetic potential when consuming jambul fruit and seeds. Studies in rats have found that the oral administration of jambul extract resulted in dose-dependent lowering of blood glucose and a protective effect on pancreatic beta cells. The mechanisms of action for these benefits appear to be stimulation of enzymatic activity involved in glucose use and the aforementioned protective effect on beta cells in the pancreas, cells that are involved in the secretion of insulin (Journal of the Science of Food and Agriculture, 2013).

Muniappan Ayyanar and colleagues from Chennai, India and Riyadh, Saudi Arabia also reviewed the pharmacology of S. cumini with respect to anti-diabetic benefit, and they mention additional animal studies in which the administration of a water extract of the seed prevented the increase in blood sugar and insulin levels induced by a high-fructose diet. While more studies in humans are necessary, a preliminary study in which jambul seed kernel extract was administered to type 2 diabetics resulted in decreased serum glucose levels, triglycerides, and total and LDL cholesterol (Complementary Therapies in Medicine, 2013). As more work is done to identify the active constituents in S. cumini and expand on human trials, jamul is likely to continue shining as a potentially beneficial anti-diabetic botanical.

Fenugreek

Fenugreek seeds (Trigonella foenum-graecum) have an extensive history of use for diabetes care in North African, Middle Eastern, and Indian systems of traditional medicine. Several studies have demonstrated the blood sugar-lowering effects of fenugreek seeds in animals as well as in healthy and diabetic humans (Journal of Ethnopharmacology, 2012). Fenugreek has multiple mechanisms of action that result in benefits for blood sugar control. The seeds contain 4-hydroxyisoleucine, an amino acid which has been shown to stimulate the secretion of insulin. Other compounds in fenugreek may play a role in influencing the intestinal digestion of carbohydrates. Fenugreek has been shown to decrease starch digestion and inhibit glucose absorption, while conferring rejuvenative benefits on pancreatic beta cells (European Review for Medical and Pharmacological Sciences, 2012).

Several recently published animal studies highlight the potential of fenugreek seeds to play a significant role in modulating blood sugar metabolism. Nawel Hamza and colleagues from France, China, and Algeria conducted a study on mice with high-fat diet–induced diabetes in which the animals were fed 2 g/kg of body weight of a water-alcohol extract of fenugreek seeds for up to 20 weeks daily. In one group of animals, treatment with fenugreek extract was initiated at the start of the high-fat diet. In a second group, treatment was initiated after the onset of diabetes. In the group in which treatment was initiated at the beginning of the high-fat diet intervention, the extract inhibited the development of diabetes. Compared to controls (untreated high-fat diet–fed mice), the group consuming the fenugreek had lower average plasma glucose, insulin, and triglyceride levels, along with less insulin resistance. In the group of mice with established diabetes, the extract again led to lower fasting plasma glucose, insulin, and triglyceride levels, with decreased insulin resistance. Thus, in both groups, fenugreek seed extract had a notable effect on parameters of blood sugar health (Journal of Ethnopharmacology, 2012).

Dr. Dinesh Puri and colleagues from the University College of Medical Sciences in Delhi, India investigated the effects of a patented compound isolated from the water extract of fenugreek seeds, referred to as GII, in diabetic rabbits (Indian Journal of Clinical Biochemistry, 2012). Rabbits were divided into three groups: subdiabetic (abnormal glucose tolerance test and fasting blood sugar levels up to 120 mg/dl), moderately diabetic (animals with fasting blood sugar levels up to 250 mg/dl) and severely diabetic (fasting blood sugar greater than 250 mg/dl).

Compound GII was administered at a dose of 50 mg/kg of body weight daily. In the subdiabetic group, GII reduced elevated fasting glucose levels to normal in 12 days. In the moderately diabetic rabbits, fasting glucose levels were normalized in 15 days. In the severely diabetic rabbits, similar results were achieved in 28 days. GII also improved HbA1c and insulin levels in the rabbits. These and previously published studies on animals and humans attest to the blood sugar-normalizing potential of fenugreek seeds.

The incidence of poor blood sugar control is at an epidemic level. With over 100 million U.S. adults over the age of 20 experiencing some degree of impaired blood sugar, the alarming prospects for the development of chronic diseases in these individuals deserve significant attention. Addressing the issue of insulin resistance through dietary intervention, lifestyle modification, nutritional supplementation, and pharmaceutical measures should be at the top of the list for public health policymakers in the United States. Botanical supplementations, such as the ones discussed here, offer potential benefits for several health parameters related to blood sugar regulation and insulin function, and thus should be considered as adjuncts in the fight to address this serious public health challenge.

Additional Ingredients on the Market for Blood Sugar Support

• Albion (Clearfield, UT): A provider of chelated minerals, Albion offers unique forms of chromium and vanadium, known for their beneficial effects on blood sugar metabolism. As a part of the company’s TRAACS line of guaranteed-chelated minerals, chromium nicotinate, glycinate chelate, and vanadium nicotinate glycinate chelate provide unique opportunities for differentiation of dietary supplements.

• Cargill (Minneapolis): Oliggo-Fiber inulin is a soluble fiber with prebiotic benefits, derived from chicory root. As a fiber, inulin does not significantly impact blood sugar levels and may promote feelings of satiety and fullness. Xtend sucromalt is a full-calorie, low-glycemic sweetener that has a lower glycemic response than sugar and is an alternative for products addressing individuals with blood sugar concerns.

• Gencor (Anaheim, CA): Trigogen is an extract of fenugreek standardized for the active component trigonelin and branch chain amino acids, which have been shown to aid fasting and post-prandial blood sugar levels. Gencinia is a branded extract of Coccinia cordifolia (ivy gourd), a vegetable consumed as part of the diet in India. A double-blind, randomized, placebo-controlled study found that Gencinia improved fasting and post-prandial blood sugar levels over 90 days.

• Horphag Research (Hoboken, NJ): Pycnogenol is a French maritime pine bark extract with antioxidant benefits. It is well-studied in animals and humans for its ability to support several health parameters in diabetes, including blood sugar control, blood pressure, endothelial function, and LDL cholesterol levels. An additional human study supports its use for improving vision in early stages of diabetic retinopathy.

• InterHealth Nutraceuticals (Benicia, CA): ChromeMate is a branded form of niacin-bound chromium that has been extensively studied for supporting healthy blood sugar, healthy cholesterol, and a healthy body weight. Zychrome brand chromium dinicocysteinate is a patent-pending chromium complex which was found to support insulin sensitivity and healthy insulin levels in a preliminary 90-day, randomized, double-blind, placebo-controlled study.

• innoVactiv (Rimouski, QC, Canada): InSea2 contains natural polyphenols from brown seaweeds, and it is marketed as a starch and sugar blocker. InSea2 works by inhibiting α-amylase and α-glucosidase, two enzymes involved in carbohydrate digestion. Clinical studies found that InSea2 consumption led to a decrease in blood sugar and insulin levels.

• Ingredion (Westchester, IL): Hi-maize resistant starch is isolated from corn that is naturally high in amylose content that, unlike most starches, resists digestion in the small intestine and passes through to the large intestine where it can act like fiber. Hi-Maize can partially replace flour in foods.

• Nutrition 21 (Purchase, NY): Chromax is a branded form of chromium picolinate supported by over 50 human clinical studies. Chromax supports glucose metabolism and insulin sensitivity, and additional research demonstrates that it supports glucose transport in the brain, contributing to improved cognitive function.

• Pharmachem (Kearny, NJ): Prenulin is a unique combination ingredient for blood sugar maintenance. It contains L-arabinose, a common sugar found in many plants with glucose absorption properties, and chromium for its insulin-balancing function. Prenulin works by inhibiting enzymes involved in the digestion of sucrose and by regulating insulin levels to achieve balanced blood sugar.

• Sabinsa (East Windsor, NJ): Fenufibers contain the fiber-rich fraction obtained from fenugreek seeds, an herb known to promote healthy blood sugar levels. Momordicin is an extract from bitter melon (Momordica charantia), a fruit with blood sugar-lowering properties. It is standardized for the compound charantin.

• Salaretin is an extract from Salacia reticulata, an herb used traditionally in the Ayurvedic tradition for controlling blood sugar levels. The active compound salacinol inhibits the activity of the carbohydrate-digesting enzymes maltase, sucrase, and isomaltase. Silbinol is a standardized extract from the bark of Pterocarpus marsupium (Indian kino), traditionally used in certain regions of India to reduce blood sugar levels. The extract contains epicatechin, which has insulin-like benefits. The plant has also been shown to benefit cholesterol and lipid balance in animal studies.

• Soft Gel Technologies (Commerce, CA): GlucoHelp is a proprietary extract of banaba leaf (Lagerstroemia speciosa) containing 18% corosolic acid, a key bioactive constituent which has been clinically confirmed to reduce blood sugar in pre-diabetic and diabetic individuals. Human trials on GlucoHelp have resulted in lowered fasting and post-prandial blood sugar levels, while also showing improvement in other symptoms of diabetes.

• Chromadex (Irvine, CA): pTeroPure is a branded pterostilbene, a polyphenol that occurs in small concentrations in blueberries. It is a phytoalexin similar to resveratrol, with significantly better bioavailability. Animal studies suggest that pterostilbene can lower blood sugar levels while supporting normal insulin function.