HEALTHY BLOOD SUGAR

Healthy Blood Sugar with Multitasking Salacia sp.

 By

 Vladimir Badmaev, MD PhD

Glucose (also called "blood sugar") itself is not a culprit in diabetes. Glucose is one of the single most important life-sustaining nutrients in the body. When glucose is not sufficiently transported from blood to the tissues or when there is a low level of circulating glucose then the tissue, including the brain is starved from one of the most important nutrients.

Glucose tissue starvation in diabetes affects the entire body and is characterized by a chronic pathological process involving multiple organs and systems. The current better understanding of diabetic pathology allows to address diabetes at multiple levels with a versatile and multitasking nutritional protocol rather than a single-track intervention approach. The main events in type 2 diabetes mellitus are as follows:

1. The continuously elevated blood glucose, due to reduced tissue uptake, reduced glucose metabolism and increased compensatory liver glucose production, fuels the citric acid cycle (called "Krebs cycle") to provide fatty acids and ketone bodies as replacement sources of energy. This process contributes to elevated blood cholesterol (especially an increase in blood triglycerides, nicknamed “ugly” cholesterol), non-alcoholic fatty liver disease (NAFLD), obesity, elevated blood pressure (metabolic syndrome) which often accompanies type 2 diabetes mellitus, as well as wasting lean body mass.

2. Excess, unutilized glucose leads to the abnormal process of glucose reaction with protein molecules in the body described in the literature as “glycation reaction.” The glycation reaction produces damaged and dysfunctional protein molecules, e.g. hemoglobin A1C. The glycation reaction products are also referred to as advanced glycation end-products or AGEs. These   products accumulate in tissues not only in diabetes but also in individuals of advanced age and with renal failure. There is emerging evidence that these compounds may play a role in vascular pathology (accelerated atherosclerosis), neurological (diabetic neuropathy), ocular (cataract formation) and renal complications (diabetic renal failure) associated with diabetes and aging.

3. Oxidative damage to DNA has been well documented in cells isolated from subjects with diabetes. Research indicates that activation of the insulin receptor by insulin or an insulin equivalent is necessary to induce cells to produce their own DNA-repair enzyme. When insulin is lacking or the insulin receptor is defective the repair enzyme is not produced. Thus, the damaged DNA is not repaired, which may lead to premature cell aging and death.

4. Free radical pathology in diabetes activates all reserve systems (body-made anti-oxidants glutathione, GSH; super-oxide dismutase, SOD; and catalase) in the body to repair DNA damage. This chain of events may deplete tissue stores of nicotinamide adenine dinucleotide (NAD), which participates in the regeneration of body-made antioxidants and activation of tissue-repair enzymes. Depletion of NAD leads to premature cell aging and death. In accelerated atherosclerosis in diabetes manifested by stroke or heart attack depletion of NAD is very prominent.

5. Clinical symptoms -- excessive thirst, hunger and excessive urination -- are common in diabetics. The excess glucose and ketone bodies in the blood act as an osmotic diuretic; excessive urination contributes to loss of water and electrolytes and thirst (polydipsia or increased fluid intake); and glucose-starved tissue may trigger negative caloric balance and an excessive appetite for food (polyphagia or compensatory appetite promoting obesity). 

6. Premature aging due to wasting of body nutrients, extensive damage to skin (insipid appearance), internal organs, rapid deterioration of the cardiovascular system (so called “small vessel” disease), and damage to the autonomous and peripheral nervous systems (neuropathy).

Salacia species (e.g. S. oblonga, S. prinoides, S. reticulata) is a plant naturally found in southern regions of India, Sri Lanka, China, Vietnam and Malaysia, and used in traditional medical systems, especially in Ayurveda, for its blood glucose-controlling property. The chemical constituents for which leaves and root bark is used in indigenous applications include polyphenols such as salacinol, kotalanol, kotalagenin 16-acetate and mangiferin. In traditional Ayurveda, Chinese and Tibetan medicine balancing several targets and mechanisms especially in chronic conditions like diabetes is prioritized to restore health.

The age-related carbohydrate metabolism deterioration is compounded by genetic factors related to impaired insulin secretion, insulin resistance and epigenetic life-style related factors, which may lead to pre-diabetes and diabetes and require a multiple-target nutritional intervention strategy. Salacia reticulate, sometimes nicknamed a “metabolic adaptogen,” is moderating several stressors that contribute to metabolism deterioration.

Salacia modifies directly or indirectly multiple metabolic targets in its role as a metabolic adaptogen. It may upregulate a mammalian protein -- peroxisome proliferator-activated receptor or PPAR-alpha -- which is produced primarily in the skeletal muscle and liver, and activates fatty acid beta oxidation suppressed in diabetic patients. Restored fatty acid oxidation provides vital energy and PPAR-alpha may also play a role in reducing chronic inflammation in diabetes. In the animal model of NAFLD/metabolic syndrome, PPAR-alpha significantly lowered pro-inflammatory tumor necrosis factor (TNF-alpha), decreased inflammation of the liver, improved fatty liver condition and lowered fasting blood glucose levels as compared to the control group.  

Another significant metabolic target modified with Salacia is hormone angiotensin. Angiotensin causes constriction of blood vessels and a subsequent increase in blood pressure and is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone produced in the adrenals that promotes sodium and water retention, increasing blood pressure.  The role of angiotensin is well recognized in the development of diabetic nephropathy and cardiovascular disease. Salacia-fed diabetic rats showed less build-up of angiotensin which lowered cardiovascular stress and cardiac hypertrophy (overgrowth and inefficiency of heart muscle) as compared to untreated controls. The Salacia angiotensin-inhibiting mechanism is important in its cardiovascular and kidney protective roles in diabetes.

One of the well-recognized metabolic roles of Salacia sp. is related to the control of the gastrointestinal enzymes involved in dietary carbohydrates and fat absorption. As an alternative to a low-glycemic index diet, there is a growing body of research supporting food supplements that slow the absorption of complex carbohydrates through the inhibition of enzymes responsible for their digestion to simple sugars which are then absorbed from the gastrointestinal tract. These products include alpha-amylase and glucosidase inhibitors and are popularly called carb blockers. Digestion and absorption of dietary fat is regulated by the action of pancreatic triglyceride lipase needed for dietary lipid hydrolysis into monomers (lipid breakdown). The resulting monomers are then absorbed from the gastrointestinal tract.  Salacia has been found in vitro and in vivo as a safe inhibitor of carbohydrate- and fat-digesting enzymes and excessive dietary carbohydrates and fat absorption, preventing fueling insulin resistance and type 2 diabetes mellitus.

An important mechanism of Salacia sp. in controlling effects of hyperglycemia is by inhibiting the carbohydrate metabolizing enzyme aldose reductase, which contributes to formation of advanced glycation end-products(AGEs) – a signature pathology in diabetes leading to dysfunctional proteins, e.g. hemoglobin A1C, cataracts, dysfunctional endothelial cells (cells lining blood vessels) and oxidative stress exhausting endogenous antioxidants. A persistently elevated blood glucose, taking place in diabetes, upregulates levels of aldose reductase, triggers conversion of glucose to fructose and increase aldolase B, an enzyme that converts fructose to methylglyoxal, a compound producing advanced glycation end-products or AGEs. AGE-containing proteins do not fold/function properly, are not properly recycled, and are associated with a number of disease conditions like diabetes and with old age.

The traditional use of Salacia sp. in blood sugar control has been recently supported with clinical studies in non-diabetic, pre-diabetes (asymptomatic or clinically silent diabetes) and clinically diagnosed diabetes.  In a double-blind, randomized cross-over study, 39 non-diabetic subjects were assessed after fasting for 12 hours, and then consuming 82 g carbohydrates in four test meals combined with 0, 500, 700, or 1,000 mg of Salacia oblonga extract respectively. Blood glucose and insulin concentrations were measured at baseline and for 2 hours after test meals. Breath hydrogen excretion for unabsorbed carbohydrates was measured at baseline and hourly for 8 hours after test meals. Compared with the control, the 1,000-mg S oblonga extract dose reduced the plasma glucose and serum insulin by 23% and 29% respectively. The lower doses of Salacia extract in the healthy population did not statistically significantly affect blood glucose and insulin levels. The breath hydrogen excretion was consistent with Salacia intake and its mechanism of inhibiting alpha-glucosidase preventing dietary sugar absorption.

With the growing importance of life-style and dietary modification in type 2 diabetes mellitus prevention, Salacia reticulata was evaluated in a randomized, double-blind, placebo-controlled study with 29 pre-diabetes and elevated cholesterol patients. The study patients received for 6 weeks either Salacia extract in a single daily dose of 500 mg/day or matching placebo together with instructions for a healthy lifestyle. The glycemic control, lipid blood chemistry, safety and tolerability were evaluated in the course of the study. A statistically significant reduction of blood levels of low-density lipoprotein cholesterol was found at weeks 3 and 6, and reduction in fasting blood glucose levels at week 6 as compared to the placebo group. There was no subjective or objective adverse effects reported in the course of the study, and consensus was that Salacia was safe, well-tolerated and potentially beneficial in the management of pre-diabetes.

The next study evaluated the effect of Salacia oblonga extract on blood glucose and insulin levels in patients with type 2 diabetes after ingestion of a high-carbohydrate meal. In a double-blinded, randomized crossover study 66 patients with diabetes consumed high carbohydrate meal either without supplementation, with 240 mg or 480 mg Salacia extract, all after a 12 hour fasting period. Serum glucose and insulin samples were measured at baseline and post meal intervals up to 180 minutes. Both doses of Salacia extract statistically significantly lowered the postprandial blood glucose levels, by 14% for the 240 mg extract and 22% for the 480 mg extract compared to the control meal; both doses of Salacia extract statistically significantly decreased the insulin response, lowering the insulin response and the peak insulin response by 14% and 9%, respectively, for the 240 mg extract, and 19% and 12%, respectively, for the 480 mg extract in comparison with the control meal. The results indicate potential benefits of Salacia as a nutritional supplement for individuals with type 2 diabetes mellitus.

Subsequent studies evaluated Salacia chinensis in one of the most prevalent condition related to long-standing diabetes, chronic kidney disease. Thirty diabetic patients with diagnosed chronic kidney disease  were randomized in a 6-month study in two groups, 15 patients each, receiving either 1000 mg of Salacia extract twice daily or placebo. The kidney function was evaluated with serum creatinine and creatinine clearance; markers of endothelial (blood vessels lining cells) inflammation and dysfunction i.e. interleukin-6 (IL-6) and serum homocysteine, and lipid profile at baseline and during the 6 months follow-up. The kidney functions statistically significantly improved in the Salacia group as compared to placebo receiving patients; in particular there was statistically significant decline in both serum homocysteine and IL-6 serum levels in the Salacia group vs. placebo indicating positive effects on the endothelial cell functions.

A similar study evaluated Salacia oblonga extract in diabetic and non-diabetic patients with chronic kidney disease. Sixty patients with chronic kidney disease (CDK) were randomized in four groups: non-diabetic receiving Salacia oblonga extract 1000 mg twice daily for six months, non-diabetic receiving matching placebo, diabetic receiving Salacia oblonga for six months and diabetic receiving matching placebo. The kidney function evaluation included blood urea, serum creatinine and creatinine clearance at baseline and after that at monthly intervals. In addition to the blood lipid profile, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at baseline, three months and six months. The Salacia 6-month regimen in comparison with placebo statistically significantly reduced the triglyceride levels by 23.66% in non-diabetic and by 17.45% in diabetic patients. In comparison with placebo, both non-diabetic and diabetic CKD patients who consumed Salacia showed statistically significant reduction in CRP levels (diabetic and non-diabetic) and IL-6 and serum cholesterol levels in diabetic only. The 6-month Salacia consumption stabilized kidney function (creatinine clearance) in both non-diabetic and diabetic patients in comparison with placebo. Salacia showed broad and positive biological action in chronically ill patients with and without diabetes, improving blood biochemistry, markers of chronic inflammation and overall systemic function.

Now imagine adding Salacia to your “coffee cup of India”! To your health!

References available upon request