Resveratrol Background
Before jumping into a discussion about the fascinating human research, however, let’s take a moment to review just what resveratrol is, in case you’re unfamiliar with it. Resveratrol is a type of natural phenol by several plants in response to injury or attack by pathogens.^3,4 These plants include grapes, peanuts⁵ and Japanese Knotweed (Polygonum cuspidatum).⁶ Resveratrol helps provide protection to the plants, at least in part, due to its demonstrated antioxidant properties.⁷ These antioxidant properties benefit humans too, as shown in research where resveratrol provided a direct antioxidant effect against free radicals, and facilitated an increase in vitamin E⁸—another powerful antioxidant.

There are two primary isomers (i.e. two forms) of resveratrol, trans- and cis-. To be clear, trans-resveratrol has been unequivocally shown to have much greater activity than cis-resveratrol.⁹ Consequently, when purchasing a resveratrol product, make sure to check the supplement facts panel to verify that the product contains trans-resveratrol. If just”resveratrol” is listed, without the trans-designation, or if cis-resveratrol is listed, you would be better off choosing a different product that lists trans-resveratrol. In any case, for ease of reading, I will drop references to trans– in the rest of this article, although it can be assumed that any mention of resveratrol will actually refer to trans-resveratrol.

Cardiovascular Health
As its first claim to fame, resveratrol has been found to have activity that may have protective effects on the cardiovascular system. In both test-tube and animal research, resveratrol has been shown to inhibit platelet aggregation (i.e. the clumping together of blood platelets). This has value since excessive or inappropriate aggregation of platelets can lead to formation of blood clots and subsequent blockages in blood vessels that result in insufficient blood flow, heart attack or stroke.¹⁰ Resveratrol can also promote vasodilation (a relaxed and expanded state of the artery that accommodates increased blood flow) by enhancing the production of a naturally occurring substance in the body called nitric oxide.¹¹

More importantly, human clinical research¹² has demonstrated that 100 mg/day of resveratrol significantly reduced arterial stiffness (a major indicator of atherosclerosis) compared to placebo, and also lowered systolic blood pressure by 5.5 points in patients with type 2 diabetes. Another human study,¹³ which used a much higher dose (2.3 g) in older adults, found that resveratrol not only improved vascular function more than placebo, but also increased the number of mitochondria.those parts of the cells that help to generate energy for our body! Another interesting cardiovascular benefit is resveratrol’s effect on Apolipoprotein B (ApoB), a primary component of many lipoproteins such as LDL (the gbad cholesterolh) that are involved in atherosclerosis and cardiovascular disease. In human clinical research¹⁴ on overweight or obese individuals with mild hypertriglyceridemia, 1000 mg/day of resveratrol for one week followed by 2000 mg/day for two weeks reduced ApoB production rate by an impressive 22 percent. In addition, flow-mediated dilatation (a measure of arterial circulation and endothelial function) was increased in human studies^15,16,17 where 10 mg to 270 mg/day of resveratrol was given. In one of the studies,¹⁸ LDL cholesterol levels were also significantly decreased.

Inflammation
In addition to showing anti-inflammatory effects in in-vitro and animal studies, resveratrol has also been shown to comprehensively suppress oxidative and inflammatory stress with as little as 40 mg/day in normal human subjects.¹⁹ This included the reduction of inflammatory markers such as TNF-alpha, IL-6, and C-reactive protein, with no changes in the placebo group. Similarly, in postmenopausal women with osteoarthritis pain, 75 mg of resveratrol twice daily significantly reduced pain and improved total well-being.²⁰

Ulcerative colitis (UC), a chronic inflammatory bowel disease, has also responded to treatment with resveratrol. In one study²¹ with 56 UC patients, those receiving 500 mg/day of resveratrol had significant symptom improvement, reduced malondialdehyde (a highly reactive oxidative stress compound), and increased superoxide dismutase (SOD), and total antioxidant capacity. In another human study²² with 50 UC patients, 500 mg/day of resveratrol also reduced the activity of inflammatory compounds, including TNF-α, hs-CRP, and activity of NF-κB. Furthermore, in a study²³ of firefighters, supplementation with 100 mg/day resveratrol for 90 days, plasma biomarkers of inflammation were reduced after a physical fitness test, including IL-6 and TNF-α. This adds further credence to resveratrol’s anti-inflammatory effects.

Immune Health/Breast Cancer Prevention
Resveratrol’s effect on immune health can be as fundamental as increasing certain circulating immune cells, or as profound at reducing the risk of breast cancer. For example, human research²⁴ was conducted to assess the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy individuals. The results were that resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating gamma delta T cells (functioning as a first line of defense and a bridge between innate and adaptive responses) and regulatory T cells—demonstrating that resveratrol has clear biological effects on human circulating immune cells.

With regard to breast cancer prevention, resveratrol may help in a couple of ways. First, resveratrol has been shown to have a dose-dependent effect on reducing the formation of mammary tumors in-vitro as a result of down-regulating DNA methyltransferases. To see if it had a similar effect in humans, a study²⁵ was conducted in which 39 adult women at increased breast cancer risk received a placebo, 5 or 50 mg of resveratrol twice daily for 12 weeks. Results were that there was indeed decrease in methylation of the tumor suppressor gene with increasing levels of resveratrol (P = .047).

In another study²⁶ of 34 overweight, postmenopausal women (BMI ≥ 25 kg/m2), the clinical effect of resveratrol on systemic sex steroid hormones were investigated, since high estrogen levels may contribute to breast cancer. The subjects received 1 g of resveratrol daily for 12 weeks. The results were that resveratrol supplementation led to an average of 73 percent increase in urinary 2-hydroxyestrone (the “good estrogen”) levels leading to a favorable change in estrogen ratios that are less conducive to the development of breast cancer. This research demonstrated that among overweight and obese postmenopausal women, a daily 1 g dose of resveratrol has favorable effects on estrogen metabolism.

Muscle Health
In a 12-week study,²⁷ older men and women (aged 65.80 years) exercised and took either a placebo or 500 mg/day of resveratrol to determine if resveratrol would have additive effects to those of exercise. Results showed that exercise added to resveratrol treatment increased the number of mitochondria, and improved muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects treated with resveratrol had an increase in muscular torque and power after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with resveratrol significantly improved muscle fiber. Together, these data suggest that resveratrol combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Cognitive Health
Research suggests that resveratrol may have cognitive health benefits in people with and without dementia. For example, the ongoing dysfunction of small blood vessels in patients with type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to various brain regions, thereby increasing risks of dementia. To determine if resveratrol could benefit cerebral circulation, a study²⁸ was conducted in which 36 dementia-free, non-insulin dependent T2DM older adults (49–78 years old) consumed single doses of resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Results were that 75–300 mg of resveratrol enhanced vasodilator responsiveness in cerebral vessels.

In another study,²⁹ 80 post-menopausal women aged 45–85 years received resveratrol or placebo for 14 weeks to examine the effect on cognitive performance and other parameters. Results were that compared to placebo, significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020). Mood also tended to improve in multiple measures. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

To test³⁰ whether supplementation of resveratrol (200 mg/ day for 26 weeks) would enhance memory performance in older adults, 23 healthy overweight older individuals were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50–75 years). Results showed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038), significant increases in hippocampal functional connectivity, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p < 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism in older adults, providing a basis for helping to maintain brain health during aging.

To determine the effects of oral resveratrol on localized cerebral blood flow, a study³¹ was conducted with which 22 healthy human adults received placebo and two doses (250 and 500 mg) of resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks. Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, and enhanced oxygen extraction. These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

Finally, a clinical study³² was conducted to determine if up to 1 g of resveratrol twice daily could benefit Alzheimer’s disease (AD) patients. The results demonstrated that resveratrol decreased CSF MMP9 (a biomarker for confirmed AD), modulates neuro-inflammation, and induces adaptive immunity— suggesting that resveratrol may be a viable target for treatment or prevention of neurodegenerative disorders.

Weight Loss
One of the reasons that resveratrol has received widespread interest is because of its ability to mimic effects of calorie restriction. To gain more insight into this effect on adipose tissue, a study³³ was conducted in which healthy obese subjects were supplemented with 150 mg/day of resveratrol or placebo for 30 days. Results showed that resveratrol significantly decreased the size of adipocytes (fat cells), with a shift toward reducing the proportion of large and very-large adipocytes and an increase in small adipocytes. Furthermore, lysosomal/phagosomal pathway and transcription factor EB were up-regulated reflecting an alternative pathway of lipid breakdown by autophagy.

Similarly,³⁴ T2DM patients received 3 g resveratrol or placebo daily for 12 weeks. Results were that there was a significant increase in both SIRT1 expression and resting metabolic rate compared with the placebo group. In patients with T2DM, treatment with resveratrol helped regulate energy expenditure, suggesting that resveratrol may have beneficial exercise-mimetic effects.

Again,³⁵ healthy, obese subjects were treated with placebo and 150 mg/day resveratrol for 30 days. The results were that resveratrol increased SIRT1 and improved the muscle’s use of fatty acids as an energy fuel, demonstrating that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. Given these results, one might think that resveratrol may aid in weight loss—and indeed this has been shown to be the case in clinical research.

Orlistat is an over-the-counter drug (also known as Alli®) designed to treat obesity by reducing the absorption of fats from the human diet. A study³⁶ was conducted to evaluate the efficacy of combining orlistat with resveratrol in 84 obese subjects over a 6-month period. The subjects consumed a diet with 500 fewer calories than their usual diet for two weeks, and were randomly assigned to four groups, placebo, resveratrol, orlistat, or the O-R combination, and they consumed the energy-reduced diet for 6-months. Results were significant weight loss of 15 lbs in the O-R group compared with 7.7 lbs in the placebo group. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination, indicating that it was the most effective weight loss treatment.

In another study,³⁷ 24 patients with metabolic syndrome received resveratrol (500 mg) three times per day before meals for 90 days. Resveratrol administration resulted in significant differences in total weight (P=0.007), body mass index (BMI) (P=0.006), fat mass (P=0.001), and waist circumference (P=0.004). In conclusion, administration of resveratrol significantly decreased weight, BMI, and fat mass.

Blood Sugar/Insulin Resistance
A study³⁸ was conducted using 480 mg/day of resveratrol or placebo for four weeks on 43 patients with diabetes who also had chronic periodontitis (i.e. gum disease). Results were that serum levels of fasting insulin and insulin resistance were significantly lower in the resveratrol group compared with control group. With regard to periodontal disease, there was also a significant difference in the gum pocket depth between intervention and control groups with resveratrol. The researchers recommended that resveratrol supplementation might be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease.

Another human clinical trial³⁹ was conducted in 32 over-weight, older adults (average age: 73 years). Participants received placebo, 300 mg/day of resveratrol, or 1000 mg/day of resveratrol for 90 days. Results were that, compared to placebo, glucose levels were significantly lower at after treatment among participants receiving either dose of resveratrol (P<0.05), and were well tolerated.

In this study,⁴⁰ 62 patients with T2DM received either an oral hypoglycemic medication, or an oral hypoglycemic medication along with 250 mg/day of resveratrol. Results were that supplementation with resveratrol for three months significantly improved the mean hemoglobin A1c (P<0.05), a measure of long-term glucose control, systolic blood pressure (P<0.05), total cholesterol (P<0.05), and total protein (P<0.05) in T2DM. The researchers concluded that oral supplementation with resveratrol was effective in improving glycemic control and may be a potential adjuvant for the treatment and management of diabetes.

In a pilot study,⁴¹ subjects with impaired glucose tolerance (aged 72 ± 3 years) received 1, 1.5, or 2 g/day of resveratrol for four weeks. After four weeks of resveratrol supplementation, results showed that post-meal (P=0.003) and 3-hour glucose levels (P=0.001) declined. Researchers concluded that, at doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and post-meal plasma glucose in subjects with impaired glucose tolerance. Likewise, in a 4-week study,⁴² T2DM patients received 10 mg/day resveratrol or a placebo. Results showed that, after the fourth week, resveratrol significantly improved insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin-signaling pathway.

Non-Alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver of people who drink little or no alcohol. Unfortunately, NAFLD is common—with easily one-third of all American adults being affected⁴³—and often causes no signs and symptoms, and sometimes no complications. In more serious cases, however, the fat that accumulates in NAFLD can cause liver inflammation and scarring.⁴⁴ In addition, NAFLD is usually associated with insulin resistance, central obesity, reduced glucose tolerance, T2DM and high triglyceride levels.

In a clinical study,⁴⁵ 50 NAFLD patients received either a 500 mg/day of resveratrol or a placebo for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. Results were that resveratrol supplementation reduced alanine aminotransferase (a marker for NAFLD) and hepatic steatosis (fatty liver) significantly more than placebo (P<0E05).

In another study,⁴⁶ 60 NAFLD patients received two 150 mg resveratrol capsules twice daily for three months. Results were that, compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol (P.0.001) alanine aminotransferase, total cholesterol (P=0.002), and insulin resistance (P=0.016). The researchers concluded that resveratrol supplementation might benefit patients with NAFLD.

Other Resveratrol Benefits
In addition to the aforementioned applications for resveratrol, there are additional benefits for this nutraceutical as well. Two such benefits are related to bone health, and for those who are smokers.

In a clinical study,⁴⁷ 66 middle-aged, obese subjects with metabolic syndrome (average age: 49.3 } 6.3 years) received oral treatment with 1,000 mg or 150 mg of resveratrol, or a placebo daily for 16 weeks to assess changes in the bone turnover marker bone alkaline phosphatase (BAP), and bone mineral density (BMD). Results were that BAP increased dose dependently with resveratrol (P<0.001), compared with placebo. Lumbar spine trabecular volumetric bone mineral density also increased dose dependently with resveratrol (P=0.036), with a significant increase of 2.6 percent in the 1,000 mg resveratrol group compared with placebo (P=0.043). In addition, changes in BAP and bone mineral density were positively correlated (P=0.027).

Smokers typically experience a state of low-grade systemic inflammation and oxidant-antioxidant imbalance. To determine whether resveratrol has beneficial effects on markers of inflammation and oxidative stress, a study⁴⁸ was conducted with 50 healthy adult smokers who alternatively were given 500 mg/ day of resveratrol and placebo. Results were that resveratrol significantly reduced the inflammatory marker C-reactive protein (CRP), triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. The researchers concluded that, because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation might beneficially affect the increased cardiovascular risk of healthy smokers.

Improving The Bioavailability And Efficacy Of Resveratrol

Now that we’ve reviewed some of the many benefits associated with resveratrol supplementation, let’s briefly consider ways to improve the bioavailability and efficacy of this valuable nutraceutical. First, take resveratrol on an empty stomach. The reason for this recommendation is a study showing that the absorption rate of resveratrol following an oral 400 mg single dose was significantly delayed by the presence of food.⁴⁹

Second, resveratrol may work better when taken together with pterostilbene (a related antioxidant) and quercetin (a flavonoid). In this study,⁵⁰ the antioxidant activities of resveratrol, pterostilbene and quercetin, and the effect of their combination were investigated in human blood cells in-vitro. When used together, the combination protected the blood cells against destruction and against depletion of the important antioxidant, glutathione. Also, the combination of resveratrol with quercetin or pterostilbene synergistically inhibited oxidative injury of membrane lipids. These protective effects may partially explain the health benefit of these bioactive micro-components when together in the diet.

Conclusion
The value of supplementation with resveratrol has moved beyond the “French paradox” and the activation of the SIRT 1 gene, associated with longevity. Human clinical research has demonstrated efficacy of resveratrol for inflammation, immune health/breast cancer prevention, muscle health, cognitive health, weight loss, blood sugar/insulin resistance, non-alcoholic fatty liver disease, and more.

Endnotes

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What Is Diabetes

Our bodies make sugar as a fuel for our cell’s energy furnaces. It releases it at constant low levels. Releasing too much at once is like flooding the engine in your car with too much gas. It makes it stall out.

For most of human history, we have had a high-fiber diet. This resulted in the carbohydrates and sugars in our diet being released very slowly and steadily into the bloodstream over many hours. Now we have almost 140 pounds of sugar per person per year being added into our diet in food processing. This represents 18 percent of our calories, causing massive spikes in blood sugar. This forces our bodies to prevent sugar from entering the cells too quickly. This change is called “insulin resistance.”

Insulin is the key that opens our cell furnaces so the sugar can get in to be burned for energy. When your cells become deaf to the insulin, the sugar builds up in your bloodstream instead. Meanwhile, the sugar can’t get into the cell to be burned for fuel and your cells are starving.

This is what occurs with insulin resistance. Meanwhile, your cells send out the message that they are energy starved, causing the body to make more sugar and more insulin. These high insulin levels, then proceed to turn the sugar into fat, causing you to pack on the pounds and become even more insulin resistant (thus the abdominal spare tire). The cycle continues until your body can no longer compensate and your blood sugar goes up. At that point you have developed diabetes, and your doctor will usually offer you whatever the newest, most profitable, and sadly often toxic medication the drug companies are marketing to them.

Why The Diabetes Epidemic?
Several factors are creating a perfect storm for diabetes developing. These include:

1. Excess sugar and white flour in the diet combined with low fiber.
2. Vitamin D deficiency, especially from the misguided advice to avoid sunshine. Sunshine makes vitamin D in our body. Low vitamin D is associated with not only diabetes, but also markedly increased risk for autoimmune illness, pain, hypertension, and other problems.
3. The obesity epidemic.
4. Decreased exercise.
5. Numerous chemicals in our environment, which block testosterone in men and increase testosterone in women.

Inadequate testosterone levels in men (imho anything under 500 ng/dl– research shows the “normal range” is to be an absurdity) have been shown to cause metabolic syndrome. This is a combination of high blood pressure, high cholesterol, and either diabetes or prediabetes. When you see a ‘spare tire’ developing on a gentleman’s abdomen, this is often the culprit. In women, the elevated testosterone is often associated with polycystic ovarian syndrome (PCOS), acne, facial hair growth, and even infertility. Metabolic syndrome improves with the treatments discussed below as well.

Testing
To screen for prediabetes, I will check a fasting insulin level. Ignore the normal range. If the fasting insulin is over 10 uIU/ ml, you should take measures now for prevention. Also check a glycosylated hemoglobin (HgBA1C). If it is over 5.8 percent, you may be developing prediabetes.

Diabetes Is Optional

In fact, this is the title of my newest book, now available on Amazon. It discusses the treatments below in-depth. Begin with simple things that help optimize blood sugar levels in your body. These include:

An Ounce Of Prevention—helping your body maintain healthy blood sugar regulation is:

1. Take a good multivitamin high in magnesium and vitamin D. My favorites are the Energy Revitalization System vitamin powder, or Clinical Essentials.
2. Cut back sugar intake. This doesn’t mean you can’t indulge your sweet tooth. In fact, chocolate in moderation is a health food. Begin by cutting out sodas and fruit juices, both of which have 3/4 teaspoon of sugar per ounce. This translates to 36 spoons of sugar in that 48 ounce “Big Burp” soda. Enjoy the whole fruit instead. Meanwhile, look at the nutritional label, and divide grams of sugar by four to see how many teaspoons of sugar are in a serving.
3. Go for walks in the sunshine. Or find other exercise, preferably outside, that you love.
4. Lose weight. This will be easier once you do the rest of the program and your insulin sensitivity improves. Research has shown that with adequate weight loss, diabetes actually goes away in 86 percent of diabetics.
5. Optimize testosterone levels in men. I will use bioidentical testosterone to bring the total testosterone up to about 900 ng/dl. In women, I would use the treatments discussed, along with the medications metformin and Aldactone to lower elevated testosterone.

Treating Diabetes

For childhood diabetes, which is a totally different autoimmune illness, insulin is a lifesaving and necessary treatment. For adult diabetics, it is a loan shark, which initially lowers blood sugar.

But because it often causes massive weight gain, it can worsen the diabetes in the long-term. So it may be necessary short-term, but it is not a good overall solution.

In my 40 years as a physician, I have found that most diabetes medications turn out to cause more harm and deaths than benefit. But routinely, physicians are not taught about the research on the drug’s toxicity until after the patent runs out and it is no longer profitable. Then the drug companies are off teaching them about the newest, most money-making, diabetes medication.

I don’t fault the drug companies for this. They are actually very nice people doing their job. Which is to make money. It is the physician’s job to be able to distinguish between what is real and truthful as opposed to slick advertising masquerading as science. But sadly, though exhorted to do so even by the past editors of the New England Journal of Medicine, they don’t realize the difference.

There is one medication that is an exception. It is an excellent medication called metformin, which is low cost and has withstood the test of time. It is highly effective, and well-tolerated. Its main toxicity is that it will sometimes cause nausea or diarrhea (lower the dose) and will routinely cause vitamin B12 deficiency unless someone is taking a multivitamin.

Hintonia Latiflora To The Rescue

From the high mountains of Central and South America, there is an amazing herb that can help lower blood sugars. This miracle botanical is an extract of the bark of a shrubby tree that grows in the Sonoran Desert. It’s been studied in detail for its ability to reverse high blood sugars for over 60 years. It has only recently become available to the North American public in a product called Sucontral-D.

There have been over a dozen studies showing how powerfully effective hintonia is!

How Does Hintonia Latiflora (Sucontral D) Work?
First, it is a rich source of a special family of flavonoids, called Coutareagenin. This polyphenol nutrient found in bark extracts unique to hintonia and appears to be responsible for many of its blood-sugar controlling benefits.

Mexican researchers also found that plant is an inhibitor of the enzyme alpha-glucosidase, which then slows the breakdown of carbohydrates in the food, mimicking the effect of a high-fiber diet.

What Does The Hintonia Research Show?
Solid research in numerous studies shows that not only can hintonia help control blood sugar and overcome insulin resistance, reducing your need for pharmaceuticals. It can also enhance the effectiveness of diabetes medications if your doctor and you decide that you need them.

For example, in a study published in the German journal Naturheilpraxis mit Naturalmedizin (Naturopathic Practice with Natural Medicine), Hintonia latiflora significantly lowered HgBA1C values (average levels of blood sugar), fasting glucose levels (blood sugar before a meal) and postprandial (after eating) blood sugar levels.

Fasting and after meal blood glucose numbers, along with A1C levels, are important because they show how much sugar circulates through your system and how your body deals with it after meals. What the research showed was amazing! Fasting and post-meal blood sugars improved by an impressive 23 and 24 percent respectively with hintonia. And glycosylated hemoglobin decreased by a remarkable average of 0.8 points (about 11 percent)! This means many people went from being diabetic to no longer being diabetic.

Impressively, by the end of the study 39 percent of those using anti-diabetes drugs could reduce their medication levels. Some were able to stop their medication entirely.

But there is more good news. Hintonia not only lowered blood sugar and often reversed diabetes. It also eliminates many of the symptoms of diabetes an impressive 73 percent over time. This is a massive change that can dramatically increase your quality of life, and well-being.

Participants also saw improvements in blood pressure, lipids, and liver values.

People with diabetes struggle with blood sugars that spike and plummet during the day and night. As this occurs, your energy, pain and mental clarity may find themselves on a roller coaster as well. One of hintonia’s greatest benefits is that it helps keep those sugars steady throughout the day and night, making life easier and contributing to long-term better glucose control.

The president of the International Diabetes Foundation was the lead author on another study that strongly recommended the use of this unique herb in treating and preventing Type 2 diabetes. Not only because of improved blood sugar control, but also because of its effectiveness in lowering cholesterol and other elements of metabolic syndrome that can lead to Type 2 diabetes.

So the bottom line? Diabetes is optional!

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Commonly over the long term in type 2 diabetes mellitus, insulin resistances increases blood glucose levels followed by a compensatory rise in circulating insulin concentrations with the latter being the body’s attempt to adapt to the former. Consequences include high blood sugar levels, prolonged high insulin levels, the appearance of medical complications and the exhaustion of the pancreas’ ability to produce insulin.

The core of the metabolic syndrome thus is the dysregulation and dysfunction involving glucose and insulin. Aside from these, secondary characteristics encompass central obesity, hypertension, and dyslipidemias—especially hypertriglyceridemia and low levels of HDL cholesterol. In addition to participating in the development of many facets of the metabolic syndrome, impairment in insulin sensitivity also appears to be involved in the aging process by promoting inflammation, endothelial dysfunction, the production of advanced glycation end products (AGE), and oxidative stress. Downstream consequences of these dysfunctions include cardiovascular disease and cancer.

Several major questions have emerged regarding the appearance of the metabolic syndrome. Western medicine, unlike, for instance, traditional Chinese and Indian medicine, tends to pursue and treat the various arms of the metabolic syndrome as distinct clinical entities. Much of the research on the syndrome within allopathic medicine over the past three decades has been aimed at arguing against this separation. Another issue is the level of insulin resistance that should be taken as requiring attention. Most clinicians consider a level of circulating glucose under fasting conditions in the range of 100–125 mg/dl to be pre-diabetic. And then there is the issue of inevitability, which is to say, does the metabolic syndrome arise as a consequence of aging?

Early Signs of the Metabolic Syndrome in Non-Diabetics

For some time, there have been questions as to what should be acceptable as a normal fasting glucose level. Circulating glucose within levels generally accepted as normal can influence brain function in an unfavorable manner and increasing hemoglobin AlC (HbAlC) and insulin levels even in the non-diabetic range may affect blood pressure adversely. Such observations lead to suspicions that minor insulin resistance predicts the early onset of many disturbed health parameters involved in the metabolic syndrome. Recently Harry G. Preuss and co-authors, of whom I am one, addressed just such questions in “Fasting Circulating Glucose Levels in the Non-Diabetic Range Correlate Appropriately with Many Components of the Metabolic Syndrome.” ¹ Those with special interests should consult that journal and a forthcoming more detailed article.

To be sure, despite access to a large number of medical records, our study faced technical limitations. Because we worked exclusively with subjects possessing non-diabetic fasting glucose concentrations, the other measured clinical values, for the most part, fell in the accepted normal range. Therefore, correlations rather than exact numbers were largely used to determine alterations in health modalities. For corroboration, however, we examined statistical differences in the various parameters between the highest and lowest quartiles associated with these fasting glucose levels. Our data in this preliminary study are representative of the general population in middle and late middle age. The hypothesis is that glucose/insulin perturbations are at the heart of the increased incidence and severity of the various constituents making up the metabolic syndrome and could hasten/ worsen the aging process. A major goal in the study was to cast light on the issue of whether aging itself is associated with the development of the components of the metabolic syndrome or whether, to the contrary, containment of fasting insulin/glucose levels to a relatively low level reduced the appearance of the metabolic syndrome components despite advancing age.

Findings
Despite the fact that the population sample consisted entirely of individuals with fasting blood glucose readings below those of diabetes, there was a clear positive correlation between rising glucose levels and metabolic syndrome components. As expected, the average, baseline values of most parameters were in the accepted normal range. Nevertheless all of the following increased more or less in tandem with rising glucose levels: body weight, body fat mass, systolic/diastolic BP, HbA1C, circulating levels of insulin, triglycerides, hsCRP (highly sensitive C-reactive protein) and along with a number of other components representing inflammation and liver health. Elevated non-diabetic glucose levels were associated with signs of augmented inflammation (increased hsCRP, white cell and neutrophil cell counts) and liver perturbations (increased ALT) proposed to play a role in the metabolic syndrome.

On the reverse side, high-density lipoprotein (HDL) showed a negative correlation, meaning that higher blood glucose levels lead to lower HDL levels. Put another way, unlike fasting glucose, when total cholesterol became the independent variable, the majority of these health parameters improved showing beneficial correlations compared to fasting glucose. However, when examining the total cholesterol minus HDL-cholesterol correlations, all benefits of total cholesterol are lost, suggesting that the benefits noted with total cholesterol are primarily due to the presence of HDL-cholesterol.

We concluded that the early onset of the various risk factors correlating with circulating fasting glucose suggests a significant role for insulin resistance in the development of the metabolic syndrome. HbA1C and insulin values are also be linked to insulin resistance, but we chose to follow a more common, clinically available marker—circulating fasting glucose levels. Fasting glucose concentrations and the levels of HbA1C and insulin are significantly correlated, therefore findings are similar whether one tests using fasting glucose levels or insulin levels.

What is the ideal range of fasting blood glucose? Based on our preliminary study, the health data were significantly better with glucose levels in the range of 67–86 mg/dL than at 98–125 mg/dL. Across a wide range of variables, lower definitely was better. Another finding, one only touched on in the provisional version of the study described here, is that aside from blood pressure, age did not seem to play a significant independent role in determining metabolic syndrome health risks and even with regard to increasing systolic blood pressure (the top figure) the influence was less than expected. Glucose and insulin levels were the primary drivers of risk factors, not age.

Conclusion
If glucose and insulin levels are the primary sources of metabolic syndrome risks, then enhancing insulin sensitivity and lowering circulating glucose levels are steps that should be taken to promote and maintain health. Fortunately, many of the means to encourage better glucose control are relatively easy. Diet no doubt is key. Sugar, refined carbohydrates and excessive calorie consumption definitely are not friends of good health. Neither are bad eating habits, which include skipping breakfast, eating late in the day and snacking, especially at bedtime. Exercise can be very helpful, particularly taking at least a 15-minute brisk walk before lunch and again later in the day. All of these measures amount to the ounce of prevention advice that actually does work, but only so long as it is followed!

References:

1. Preuss, H. G., Clouatre, D, et al. Fasting Circulating Glucose Levels in the Non-Diabetic Range Correlate
2. Appropriately with Many Components of the Metabolic Syndrome. The Original Internist June 1, 2016, pp. 78ff.

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Bitter melon grows in the tropical and subtropical areas of the East Africa, Asia, India, South America and the Caribbean. It is used traditionally as both food and medicine in all of these areas. Momordica charantia goes by many names and is known as bitter melon, bitter gourd, balsam pear, karela, and pare. Most Westerners will identify bitter melon as looking like a pale green or green cucumber with warts. Indian varieties may be whitish to gray-green, as well. Commercial cultivars can range up to a foot or more in length, whereas wild bitter melon varieties may measure only an inch or so, more than making up for their small size with greater bitterness and intense flavor. The gourd becomes more bitter as it ripens. As a food, unripe bitter melon is used fresh in salads, cooked into soups and curries, employed as a flavoring for eggs, meat and so forth.

Long popular as part of the cuisine of South Asia and China, bitter melon today is conquering new gastronomic territories. Okinawans, renowned for longevity, are extremely fond of a small local variety reputed to confer health benefits. From Okinawa and other sources, bitter melon is becoming increasingly widespread on the Japanese mainland. This reflects an East Asian trend typical of Korea as well as Japan: Highly flavored and colored nutrient-dense foods are being adopted as everyday sources of health. Hence black and red rice, black garlic, bitter melon and other such foods and condiments are being embraced.

A Plethora of Benefits
Almost every part of the Momordica charantia plant has been used in traditional medical practices, including not just the fruit, but also the leaves/vines, seeds and roots. Folk and traditional systems often suggest bitter melon for microbial infections, sluggish digestion and intestinal gas, menstrual stimulation, wound healing, inflammation, fever reduction, hypertension, and as a laxative and emetic. All these benefits are from a plant with fruit that has been proven safe by centuries of oral consumption. The only concern generally of note is that bitter melon seed consumption is not recommended for those seeking to become pregnant.

In South Asia, bitter melon is recommended to support immune health. Some of the effects are direct and some are indirect. Benefits include the inhibition of the growth of a variety of gram-negative and gram-positive bacteria, including E. coli, Salmonella, Staphylococcus, Streptococcus and H. pylori. Extracts, similarly, according to in vitro studies, appear to have an impact on a number of viruses. For instance, bitter melon constituents may prevent viral penetration of the cell wall. Immune effects include support for healthy T-helper cell ratios, natural killer cell populations and related mechanisms.

With current problems involving overweight and obesity, some of the more attractive actions of bitter melon involve controlling weight gain in the face of the consumption of excessive calories. Animal studies have demonstrated that bitter melon can reduce insulin resistance and visceral obesity caused by a high-fat diet. Similarly, bitter melon may be protective against many damaging results of high fructose diets, including diet-induced hyperglycemia, hyperleptinemia, hyperinsulinemia, and hypertriglyceridemia. The American Medical Association currently is recommending that added sugars should not account for more than five percent of the diet, yet added sugar, especially fructose and “corn” sugars, are found everywhere in the American food supply, although often hidden. Bitter melon may offer some nutritional protection against these added sugars.

Traditional uses and preclinical research provide a very positive picture of bitter melon. Human trials have confirmed many of these findings. In clinical trials, the fresh fruit, its freshly squeezed juice and the homogenized suspension of bitter melon have led to significant reductions in both fasting and postprandial blood glucose. The caveat is that the successful trials in the literature as a rule have used almost exclusively fresh preparations. For whatever reasons, dry extracts have not fared well in clinical trials. Perhaps this is due to the fact that dry extracts usually are concentrated for charantins even though, according to some research, charantins, the saponins commonly selected for “standardized” preparations, may be inactive or only weakly active. Another possibility is that the most active compounds in bitter melon rapidly deteriorate in most dried powders and extracts.

If you like the taste of bitter melon, the success of freshly prepared materials in clinical trials is great news because it means that the vegetable may deliver not just a taste treat, but also health benefits when consumed raw and cooked in salads, soups, curries, egg and meat dishes, etc. There also remains another option. Recent research suggests that a special form of bitter melon, especially with proper handling, may deliver on the promise of the fresh material even when dried and delivered in capsules and tablets.

Sometimes Wild Is Better!
With many grains, fruits and vegetables, wild genotypes retain healthful qualities that have been bred out of cultivated varieties. For instance, Khorasan wheat (Kamut), a much older form of wheat, provides more protein, minerals and more complex carbohydrates with lower gluten levels than is true of modern wheat. Similarly, carrots initially most often were purple rather than orange because of the vastly greater amounts of phytonutrients in the form of anthocyanidins. Lettuce was more bitter, and so forth and so on.

With bitter melon, much the same is true. There are literally hundreds of different forms of bitter melon found in China and India. In many ways, the most interesting of these nutritionally are the “wild” forms found in India.

Recently, a comparative trial in animals looked specifically at the differences among commercial herbal extracts of bitter melon of Chinese, Indian and Indian wild genotype origin. The goal was to establish benefits with regard to blood sugar and insulin regulation and also parameters linked to blood pressure. Very little work has been performed with wild genotypes of bitter melon, even though there are a great many of these in India alone. Most information available tends to cover topics such as the effect of the wild forms on inflammatory responses. Hints in the literature suggest that the blood sugar effects of some of these wild genotypes could be more potent than in the cultivars commonly used for extraction. For instance, it has been found that extracts of bitter gourd activate cellular machinery to regulate energy production (technically, Amp-activated protein kinase) and the way that fats are handled by the liver. These components can account for as much as 7.1 g/ kg of the dried wild material.

In a just published trial that did look at wild bitter melon, over a period of 60 days the effect of an extract from the wild genotype of bitter melon offered commercially under the name Glycostat proved to be more efficacious than the varietals typically used in Chinese and Indian preparations and certainly more consistent in influencing all the health parameters tested. Wild bitter melon was compared with two commercially available Chinese and Indian preparations in an animal model with a standard test called a Glucose Tolerance Test (GTT). In this test, a fixed amount of glucose is consumed and then the amount that accumulates in the blood (Area Under the Curve/AUC) is measured and the change (delta) is calculated. A smaller change is good because it means that the body is rapidly taking the glucose into the tissues and that there is good insulin sensitivity. All the bitter melon extracts reduced the increase in blood sugar. However, wild bitter melon was superior to both the Chinese and Indian extracts and it was the only extract to deliver statistically significant results. Of particular note, this greater benefit was achieved without elevating insulin levels.

Other interesting findings included the wild extract’s significant influence on the nitric oxide system (influencing whether the blood vessels can dilate), a system that controls blood fluid volume known as the renin-angiotensin system (RAS) and the closely related angiotensin converting enzyme (ACE) activity. These three systems and activities influence blood pressure and cardiovascular health and in each of them, wild bitter melon either was the only extract that exhibited significant activity or it was more active compared to the Chinese and Indian extracts.

Concluding Thoughts
Bitter melon is yet another example of a traditional food and health aid that has made good when tested against modern Western standards. The benefits are real in areas such as blood glucose and blood pressure support—with the caveat that until now bitter melon needed to be eaten in large amounts or the freshly prepared juice consumed regularly in order for the benefits to be realized. Extracts and dried powders have been less successful, perhaps because unstable or for other reasons. A specially prepared wild bitter melon extract produced with special processing appears to have solved this limitation. Wild bitter melon extract supports both blood sugar and blood pressure health, all without the bitter taste.

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