In a 2003 study review done by Harvard Medical School researchers, 108 clinical trials examined no less than 36 different botanicals with potential anti-diabetic properties. Together with another 9 trials done using supplements, these studies tested 4,565 diabetic patients. The review concluded that 76% of 58 controlled studies showed improved glucose control. Many more studies have been added since 2003 as botanical research has intensified.
New Mechanisms
The mechanisms for NIDDM have also undergone vigorous research over the past few years. Primary mechanisms of the past focused on insulin and glucose sensitivity at the cell membrane and the health of pancreatic beta-cells. Recent research has revealed several new complexities. Originally linked to obesity, leptin is now thought to be involved in hypothalamic energy regulation, stimulation of glucose transport, and the inhibition of insulin secretion by pancreatic beta-cells. Two more recently-discovered hormones are resistin and adiponectin. Resistin has been linked to glucose tolerance and hepatic insulin resistance. Adiponectin is linked to glucose regulation and lipid metabolism. Produced in fat cells, both resistin and adiponectin also apparently mediate PPAR-gamma: Resistin upgrades and adiponectin downgrades insulin resistance through PPAR modulation. Enzymes are now thought to be a critical part of the mechanism. One enzyme seemingly instrumental to leptin regulation tangential to PPAR-gamma repression is SIRT1. Sirtuins have been implicated in the diabetic mechanism because of their ability to affect genetic expression related to issues of degenerative glucose and insulin metabolism.
SIRT1 appears to balance glucose levels by modulating the PGC-1alpha molecule. PGC-1alpha is a transcriptional co-activator. When SIRT1 was inhibited in vivo this increased hypoglycemia, increased glucose and insulin sensitivity as well as increased free fatty acids and cholesterol. On the other hand increased SIRT1 expression reversed these effects, but only in the presence of PGC-1alpha during fasting. Yet another recently-discovered hormone implicated in both forms of diabetes is amylin. Amylin is co-secreted with insulin and complements insulin's actions together with providing a feedback-response mechanism. Other components complicating these mechanisms include glucocorticoids and circulating lipids. These various mechanisms compound to make NIDDM associated with stress, hypertension, visceral adiposity, elevated triglycerides, small dense low-density lipoproteins, decreased HDL, and of course diets high in refined sugars and low in fiber.
Whole Foods and Exercise
Most physicians now realize that eating whole foods and exercising is one of the best ways to stabilize blood glucose levels. Whole foods contain various soluble fibers such as pectin and beta-glucans, known to slow glucose absorption rates and bind LDL cholesterol.
Oats: Avena sativa L.
Oats are one of the best fiber sources and potent sources of beta-1,3-d-glucan and beta-1,4-d-glucan, as well as avenanthramides-polyphenols shown in studies by Tufts University and USDA Human Nutrition Center as antioxidant and LDL-oxidation protective. In a Finnish randomized controlled study of twelve NIDDM patients, eating higher beta-glucan oat snacks showed lower glucose fasting and load tolerance levels than controls. The mechanism includes a slowing of digestive enzyme activity and lipid modulation. Other studies have illustrated oat bran's ability to decrease total cholesterol and LDL levels on top of lowered post-meal glucose and insulin. There are several products that offer higher fiber versions of oats. Bran concentrate can offer up to 50% beta-glucan. Nature can step up the beta-glucan as well. A new variety of high beta-glucan/high avenanthramide oats called HiFi oat was bred by the North Dakota State University over the past few years. HiFi® can be up to 50% higher in beta-glucan than most other oats.
Mushrooms
Medicinal mushrooms contain beta-1,3-d-glucans with beta-1,6-d-glucan and alpha-1,4-glucans-contributing to their glycemic and immune function benefits. In addition to the prized beta-d-glucan, mushrooms contain various enzymes, sterols and triterpenes. Improved insulin sensitivity, increased glucose uptake and binding, insulin-like activity and enhanced immune effects have been seen in among the multitude of mushroom studies. Research has found anti-diabetic action among oyster mushroom, maitake, cordyceps, Tremella fuciformis, Agaricus blazei Murrill, and Jelly Ear fungus Auricularia. Maitake appears to have the most research. Glycemic benefits have been shown in a host of mushrooms.
Pinus pinaster
An extract from the bark of the French marine pine tree-a tree indigenous to France. It has been the subject of more than 200 studies, 50 of which were human. The mechanism appears to be related to slower glucose uptake, improvement in blood lipids, and increased micro-circulation. The large procyanidin molecules inhibit alpha-glucosidase-the enzyme necessary for glucose absorption.
Fenugreek
Trigonella foenum-graecum is indigenous to west Asia, southeast Europe and north Africa. It is also cultivated in many other areas. A traditional herb used for glucose control, fenugreek has a long history of success. The crushed plant's seeds contain alkaloids, coumarins and saponins. Its principle active constituent is 4-hydroxyisoleucine. In one study 17 of 21 NIDDM patients had blood glucose reductions averaging 30 mg/dl after being administered 15 grams of ground seed of fenugreek. In another, 60 NIDDM volunteers reduced fasting blood glucose levels from an average of 151 mg/dl to 112 mg/dl after 24 weeks using a 12.5 mg dosage twice a day. Other studies have confirmed fenugreek's action of reducing fasting blood sugar levels together with total cholesterol and triglycerides.
Caiapo
Ipomoea batas is a white sweet potato indigenous to South America and cultivated particularly Japan. The highly glycoprotein skin of I. batas has been shown to have anti-diabetic action in both animals and humans. In 2002 18 male NIDDM subjects were treated either with placebo, low (2 grams/day) or high (4 grams/day) doses of caiapo powdered tablets for six weeks. The high-dose group showed 13% reduction in fasting glucose, a 42% increase in insulin sensitivity and a 72% increase in glucose tolerance. In another study, 61 NIDDM subjects were given either 4 grams of caiapo or placebo daily for 12 weeks. Fasting glucose levels decreased from 143 mg/dl to 128 mg/dl averages in the caiapo group while remaining unchanged in the placebo group. Two-hour glucose levels were also significantly reduced in the caiapo group.
Gurmar
Gymnema sylvestre has been in use for thousands of years in Ayurvedic medicine. Its leaves contain gurmarin, gynmenic acids, stigmasterol, quercitol, and various glycosides, resins and saponins. Both the whole plant and its GS4 water-soluble extract fraction have been noted for increased glucose sensitivity and uptake, higher beta-cell count and increased insulin levels. G. sylvestre has been used traditionally for both NIDDM and IDDM (type-1). Interestingly, G. sylvestre has an apparent ability to suppress sweet taste stimuli by blocking taste receptors. This apparently comes from its saponins. Its anti-sweetness effect was shown to decrease sweet snack consumption. G. Sylvestre's diabetic research appears solid. In a 1990 study 27 insulin-dependent IDDM patients were given 400 grams per day of GS4 over a 10-12 month period. Insulin requirements and glycosylated hemoglobin levels both decreased significantly as compared with control subjects. Other smaller studies have shown G. sylvestre's ability to lower fasting glucose and glycosylated hemoglobin. In vitro G. sylvestre appears to stimulate insulin release by increasing pancreatic beta-cells' membrane permeability.
"Cinnamon"
Cinnamomum cassia shouldn't be confused with "true" Ceylon cinnamon Cinnamomum verum-the variety used for cinnamon sticks. C. cassia is by far more active and also the most used on retail shelves. C. cassia contains cinnamaldehyde, coumarin, cinnamyl acetate and 2-hydroxycinnamaldehyde. In vitro analyses reveal the extract and a water-soluble flavanoid polyphenolic polymer contains insulin-like activity, showing glucose uptake, glycogen synthesis and increased phosphorylation of the insulin receptor. Other bioactives have stimulated autophosphorylation of truncated insulin receptors, apparently inhibiting PTP-1-known to shut down the insulin receptor. In a 2003 double-blind study of 60 NIDDM volunteers C. cassia reduced mean fasting serum glucose by 18-29% with significant lipid reductions after forty days at different dosages(31). In a 2006 random double-blind study of 79 NIDDM, patients took either water-extracted cinnamon equivalent to 3 grams every day for four months or a placebo. Fasting glucose levels reduced 10.3% for the cinnamon group as opposed to 3.4% for the placebo group. Though a 2006 study of postmenopausal NIDDM women curiously showed little effect(33), a 2007 study of 14 healthy subjects taking 6 grams of cinnamon in pudding after meals significantly delayed food stomach emptying and reduced post-prandial glucose levels.
Garcinia Cambogia
The rind of this small fruit grown in Asia contains hydroxycitric acid (HCA), which has undergone several human and in vivo studies showing appetite reduction, increased fat oxidation, lower triglycerides, reductions in body weight(35), substantially decreased leptin levels and more recently, lower fasting glucose levels.
Bitter Melon
Mormordica charantia is another traditional botanical medicine. Constituents charantin, vincin and polypeptide-p from the juice of the unripe fruit have been reported to have anti-diabetic activity. Though still under debate, mechanisms for bitter melon appear to be related to polypeptide-p's insulin-like behavior along with glucose absorption inhibition, regulation/stimulation of insulin and improved glycogen-synthesis. Though human studies have been scant, a number of in vivo studies have shown bitter melon to have a 30% to 48% lowering effect on blood glucose levels.
Prickly pear cactus
Opuntia streptacantha and Opuntia ficus indicaenus-also referred to as nopal-grows primarily in the arid climates of Mexico and the Southwestern U.S. In reviewing the literature on both human and animal studies, it appears that nopal's action glucose tolerance effects appears to stem from its ability to modulate LDL cholesterol. Various clinical trials done in Spain with NIDDM patients concluded that nopal reduced serum glucose levels following dextrose challenges.
Coccina indica
C. indica is a creeper growing primarily in India and Bangladesh. Extracts from the roots and leaves are used. C. indica appears significantly high in pectins, chitooligosaccharide-specific lectin and a number of other components. In a 1998 study, 500 mgm/kg body weight of dried extract was given to 30 NIDDM patients for six weeks. Increased-glucose control was concluded. From the data it appeared that C. indica's insulin-like activity was related to modulating several glyolytic and lipolytic enzymes, and the repression of the glucose-6-phosphatase enzyme. In a six-week trial of 32 NIDDM patients, 10 of the 16 patients taking C. indica showed significant improvement in glucose tolerance while none of the 16 control group showed improvement. A number of in vivo studies have shown C. indica's ability to lower fasting glucose levels, some as low as 24%.
Aloe vera
The dried gel from the Aloe vera (family:Aloeaceae) plant has been shown useful in three studies on NIDDM. Five phytosterols lophenol, 24-methyl-lophenol, 24-ethyl-lophenol, cycloartanol, and 24-methylene-cycloartanol together with water-soluble fiber glucomannan, appear to be the active constituents. Blood sugar reduction of up to 55% has been shown in in vivo research. The mechanism is thought to be related to its beta-cell protective effects, inhibitory effects on glucose-absorption speed and a modulation of liver enzymes. A half-teaspoonful of aloe daily for 4-14 weeks decreased fasting glucose levels from a mean of 273 mg/dl to 151 mg/dl for five NIDDM patients. Two other human studies have confirmed similar effects with one teaspoon daily.
Pterocarpus marsupium
One of the most illustrative studies showing botanicals' NIDDM effects was published in 2005. In a double-blinded randomized study comparing Pterocarpus marsupium with the popular diabetes drug tolbutamide, 365 newly-diagnosed or untreated NIDDM patients were treated either with P. marsupium or tobutamide for 36 weeks. 86% of the Pterocarpus treatment group achieved glycemic control while 94% of the 177 tolbutamide-treated patients achieved control, based on fasting and post-prandial blood glucose (with average reduction ranges of 23-31% and 28%-34% respectively). As other trials of this botanical have confirmed, there were no adverse effects of Pterocarpus.
Pterocarpus has a very long history of use in India for diabetes. The whole tree bark is used as a powder or cut piece. Sometimes it is administered as a cup carved from the tree's bark. Water soaks in the cup overnight to absorb the extract and consumed the next morning. The mechanism for Pterocarpus-with constituents thought to be epicatechin, marsupin and pterosupin-is not well understood.
Other Botanicals
Other botanicals with limited research but plenty of anecdotal and historical traditional use for in blood sugar management include Solomon seal, Eucommia, Rehmannia; plum extract, miracle fruit (Synsepalum dulcificum), litchi fruit, cornus fruit (cornelian cherry or dogwood fruit), goji berry, black rice extract, stevia, Astragalus sp., Rhodiola crenulata and Lo Han Guo (Siraitia grosvenori). Spice extracts from the Labiatae family-including sage, oregano, rosemary, and lemon balm-also apparently inhibit alpha glucosidase. Neem (Azadirachta indica) has also shown anti-diabetic effects in research and traditional use. In 2007 a study of 10 NIDDM patients showed neem's significant hypoglycemic effects.
