It improves blood sugar, insulin sensitivity, glucose metabolism and now . . .

Cinnamon Cools & Calms
Intestinal Inflammation

New research has found that cinnamon extract
can improve lipoprotein and triglyceride levels
By Will Block

W ould you ever even dream of setting your body on fire? Of course not. But your body does it for you, in a manner of speaking. Inflammation (to set on fire, from the Latin word inflamatio) is your body’s biological emergency-medical response to harmful stimuli, such as irritants, pathogens, or damaged cells. However, it is a double-edged sword. On one edge, without the inflammatory-response mechanism wounds and infections would never heal, and thus the progressive devastation to tissue would ultimately terminate our survival. On the other edge, inflammation plays an active role in many diseases, including degenerative ones such as cardiovascular disease, Parkinson’s disease, osteoarthritis, autoimmune diseases, and diabetes. Inflammation heals or harms, depending on the context and the circumstances.


Inflammation heals or harms,
depending on the context and the
circumstances.


Mediating the Forces of Inflammation

The fundamental problem arises when the beneficial inflammatory process goes on—like an out-of-control forest fire (controlled fires have benefits … Smokey the bear was wrong!)—even after its job is done. This is more likely to occur as we get older. Fortunately, the body has its own mediating mechanisms, involving certain proteins, such as tristetraprolin (TTP). This protein undermines pro-inflammatory effects by suppressing messenger molecule (mRNA) encoding, thereby quenching the flames of too much inflammation. When TTP isn’t expressed, as indicated by reduced levels in the fats of obese people with metabolic syndrome and in the brains of suicide victims, the results can be harmful to outright dangerous.

The Intestines are a Source of Inflammation

Data has been gathering for TTP, reporting that it can be induced by insulin (an anti-inflammatory hormone) and cinnamon extract in fat cells.1 But there are other proteins, including signaling proteins, that influence inflammation, and now a new report by Richard A. Anderson, Ph.D. and colleagues has found that water-soluble cinnamon extract (CE) lessens inflammation associated with intestinal dyslipidemia—good news indeed.2


Cinnamon extract inhibited the
postprandial (after a meal)
overproduction of apoB48-containing
lipoproteins and serum
triglyceride levels.


This is important for several reasons. First, the pro-inflammatory cytokine, tumor necrosis factor (TNF-α)—a signaling protein—stimulates the overproduction of intestinal apolipoprotein B48-containing lipoproteins. Second, TNF-α is a link between obesity, insulin resistance, and metabolic syndrome. Third, inflammatory biomarkers are associated with the development of type 2 diabetes and cardiovascular disease.

In our bloodstream, there are five groups of lipoproteins, including low-density lipoproteins (LDL or “bad cholesterol”). Among its functions, LDL carry cholesterol to tissues, which they do through their primary fat (lipid) binder apolipoprotein B (aka apoB). In plasma, apoBs exist in two main isoforms; apoB100, which is created entirely in the liver, and ApoB48, which is synthesized by the small intestine. Here lies the problem.

Inhibiting Intestinal Pro-Inflammatory Factors

Pointing to a solution in the current study, Qin et al. (Anderson is the lead author) found that CE lessens the disruption in the amount of lipids in the blood (dyslipidemia) induced by TNF-α in hamsters, and also that CE inhibits oversecretion of apoB48-induced by TNF-α in intestinal cells (enterocytes).

In hamsters, oral treatment with CE at 50 mg per kg of body weight* inhibited the postprandial (after a meal) overproduction of apoB48-containing lipoproteins and serum triglyceride levels. The researchers were also able to show an equivalent result, ex vivo, using labeling studies. What they found was that CE (at 10 and 20 μg/ml) inhibited the oversecretion of apoB48 induced by TNF-α treated intestinal cells. Insulin insensitivity, at the level of the intestine, and abnormal insulin signaling are important underlying factors in intestinal overproduction of apoB48 (an atherogenic) in the insulin-resistant state.


* The human equivalent is about 500 mg of CE per day.


Then, to determine the molecular mechanisms involved, TNF-α-treated primary intestinal cells isolated from chow-fed hamsters were incubated with CE (10 μg/ml). The researchers then examined the expression of the inflammatory factor genes (IL1-β, IL-6, and TNF-α), insulin signaling pathway genes, insulin receptors, and other factors. CE was found to reverse the negative effects of TNF-α involving inflammatory factors and insulin signalling pathways.

CE treatment also decreased the mRNA expression of the inflammatory factors, improved the mRNA expression of insulin receptors, and generally improved other factors associated with intestinal inflammation. Altogether, the findings suggest that CE reverses TNF-α-induced overproduction of intestinal apoB48 by regulating gene expression involving inflammatory, insulin, and lipoprotein signaling pathways.

In summary, this new study strongly suggests that CE helps prevent the elevation of circulating triglyceride-rich lipoproteins in whole-body and intestinal insulin resistance. This is no wonder. Accumulating evidence has indicated that dyslipidemia is associated with insulin-resistant states resulting from overproduction of both intestinal and hepatic triglyceride-rich lipoproteins, and the delay of their hepatic clearance. CE also reduces inflammatory-related dyslipidemia and the increased risk of cardiovascular failure.


CE also reduces inflammatory-related
dyslipidemia and the
increased risk of
cardiovascular failure.


The Many Charms of Cinnamon

It has been said that the third time is the charm. If that’s true, then cinnamon has provided charm again and again and again . . . . In addition to the ability of cinnamon to improve inflammation related to intestinal dyslipidemia, it has also been found to:

  • Potentiate the effects of insulin (it works almost as well as insulin)—cinnamon and insulin act together synergistically3

  • Mimic the effects of insulin4

  • Regulate blood-sugar levels5

  • Prevent the formation of damaging oxygen radicals in the blood stream

  • Stimulate glucose uptake by our cells

  • Manage blood-sugar metabolism6

  • Help reduce blood pressure7

  • Help improve cognitive functions (because it mimics insulin)8

  • Help regulate fatty acids9

  • Help reduce blood sugar and cholesterol levels10

  • Improve insulin sensitivity11,12

  • Improve glucose tolerance13

  • Help prevent advanced-glycation endproducts

  • Activate PPARs,14 the doorways to major mitochondrial benefits; PPAR gamma is a major target for the treatment of type 2 diabetes

You should know that scientists have determined that there are parallel and complementary benefits that derive from the consumption of mulberry extract. (Please read the sidebar below,“Mulberry Also Helps Control Blood Sugar, and More.”) So if there is one supplement you need to add to your regimen, you can’t go wrong with one containing cinnamon and mulberry extracts.

Mulberry Also Helps Control
Blood Sugar, and More

The leaves that silkworms love contain agents
that can significantly improve our health

Ille salubris aestates peraget, qui nigris prandia moris finiet.
— Horace, Satires, 35 B.C.

In case your Latin isn’t what it used to be, that quotation says, “A man will pass his summers in health, who will finish his luncheon with black mulberries.” And you thought mulberries were for the birds. Actually, birds are very fond of mulberries. Humans are less so, however, because, although mulberries are sweet and edible, they’re considered rather insipid, as berries go. With such an abundance of delicious blackberries (which mulberries resemble), raspberries, strawberries, blueberries, etc., most people just don’t care much for mulberries and are happy to let the birds feast on them.

But let’s get back to the quotation. The great Roman lyric poet Horace (his real name was Quintus Horatius Flaccus, and he lived from 65 to 8 B.C.) may have been onto something. The folk medicine of his time encompassed countless herbal remedies—in fact, botany and medicine were pretty much one and the same in those days, and remained so for about another 16 centuries—and a great variety of therapeutic benefits were ascribed to them. Some of the claims were specific, whereas others, such as Horace’s couplet about mulberries, were vague, leaving us to wonder just what it was that the ancients saw in these plants.

There was probably at least a germ of truth in all their claims, though, and many of these claims have withstood the tests of time and scientific scrutiny to become accepted by modern medical practitioners as both genuine and significant. In many cases, we can now pinpoint the chemical compounds that gave these ancient herbal remedies their biological activity. Sometimes we extract the compounds from the plants so that they can be used in supplements or drugs, and sometimes we synthesize them in the laboratory for the sake of greater purity or lower cost.*


*A favorite practice of the pharmaceutical industry is to take a biologically active natural substance and synthesize novel chemical derivatives that have similar biological activities (often more pronounced, but usually with unwanted side effects that the original substance did not have). These derivatives, belonging exclusively to the drug company that made them, can be patented and sold at high prices as prescription drugs.


Mulberry Fights Arterial Plaque

Scientists in Japan have pinpointed a number of biologically active compounds in extracts of the leaves of the white mulberry, Morus alba, a plant that silkworms are crazy about.1 Not that the silkworms care, but the mulberry-leaf extract turns out to be effective in suppressing the progression of atherosclerosis, the buildup of cholesterol-rich plaque in our arteries.2 It does this, apparently, by inhibiting the oxidation of LDL-cholesterol (low-density lipoprotein, the “bad cholesterol”), which is a major factor in the development of atherosclerotic plaque.

The Japanese researchers reached this conclusion based on their observations of the antioxidant effects of the mulberry extract on LDL-cholesterol taken from both rabbits and humans. They believe that the agents primarily (but not exclusively) responsible for this effect are two closely related compounds, isoquercitrin and astragalin. The former contains, as part of its molecular structure, the well-known antioxidant flavonoid quercetin, which is found in many foods and in a variety of nutritional supplements.

In studying the antioxidant effects of the whole mulberry-leaf extract and, separately, of the compound isoquercitrin, as well as of the compound quercetin (which is not found as such in mulberry), the researchers observed that all were effective but that isoquercitrin was somewhat less effective than the same amount of quercetin. They also reported, however, that when isoquercitrin is ingested (by mice), it is largely metabolized to quercetin. Thus, although quercetin is not found in mulberry, mulberry is still a good source for it (and the silkworms still couldn’t care less).

Mulberry Fights Diabetes

The antioxidant, antiatherosclerotic effects of mulberry are gratifying, of course (and here we’re making the assumption that the effects seen in laboratory and animal experiments would be seen in actual human beings as well), but there’s more to the story than that. Mulberry leaves have long been used in Chinese medicine for the prevention and treatment of diabetes, because, as we now know, they contain chemical compounds that suppress high blood sugar levels (hyperglycemia) following a carbohydrate-rich meal.

Controlling blood sugar (glucose) levels is vitally important. When these levels rise sharply, as they do after ingesting foods with a high glycemic index, such as potatoes or sweets, the body responds by producing more insulin to deal with the overload. But if this demand for more insulin occurs too strongly too often, the ability of the pancreas to produce enough insulin may become impaired, and our cells may become resistant to insulin as it tries to do its job of facilitating glucose transport through the cell walls. The result is insulin resistance, a dangerous condition that, if unchecked, leads to type 2 diabetes. Its primary cause is obesity. Generally speaking, if you are obese, your risk for diabetes is high; if not, it’s low (unless you happen to have a genetic predisposition for diabetes).

There Are Different Ways to Attack Diabetes

Diabetes is a complicated disease with many ramifications, among which are increased risks for atherosclerosis and cataracts, both of which are strongly linked to oxidative stress caused by insufficient blood levels of antioxidants. The fact that people with diabetes have significantly lower antioxidant levels than normal suggests that this disease is affected by oxidative stress—a view that is supported by the well-known clinical efficacy of lipoic acid (“the antioxidant’s antioxidant”) in preventing and treating diabetes. It is reasonable to suppose that many other antioxidants are also beneficial against diabetes, and some have indeed been proven to be effective. One of these is the compound EGCG (epigallocatechin gallate), a green-tea polyphenol that also happens to be a potent anticarcinogen.


Mulberry leaves have long been used
in Chinese medicine for the
prevention and treatment of
diabetes; they contain compounds
that suppress high blood sugar levels.


But there are other therapeutic approaches to diabetes as well. One is through compounds that mimic the effects of insulin, such as MHCP (methylhydroxychalcone polymer), a constituent of the cinnamon. Another approach is through compounds that inhibit the action of intestinal enzymes called alpha-glucosidases, whose function is to break disaccharides (double sugars, such as sucrose, maltose, and lactose) down to monosaccharides (single sugars, such as glucose, fructose, and galactose) so that they can pass through the intestinal walls into the bloodstream.

Mulberry Controls Blood Sugar

Another research group in Japan has found that white mulberry leaves contain compounds that inhibit these intestinal enzymes.3 In experiments with normal rats, they found that certain nitrogen-containing sugars in mulberry-leaf extract, notably one called 1-deoxynojirimycin, strongly inhibited the intestinal metabolism of disaccharides (especially sucrose), thereby restricting the amounts of monosaccharides that entered the circulation. They also found that pretreating the rats with mulberry extract before feeding them carbohydrates significantly suppressed the normal postprandial (after-meal) rise in blood glucose levels.

This beneficial effect occurred in a dose-dependent manner. The doses were, however, very large: 0.1–0.5 g/kg of body weight, which, for a 75-kg (165-lb) human, would be 1.6–8 g. (A lower dose, 0.02 g/kg, corresponding to 243 mg for a human, was ineffective.) Nonetheless, the researchers suggested that mulberry extract might be beneficial in preventing human diabetes by suppressing intestinal alpha-glucosidase activities.

Mulberry Does Better than Prescription Drug

Some would say that there’s not much difference between rats and humans—a statement that can be interpreted on different levels. On the level of pharmacology, it is generally (but not always) true that there’s not much difference between the two species. Ultimately, however, there is no good substitute for clinical trials done on actual humans. Fortunately, a research group in India has done that for mulberry, using leaves from Morus indica (Indian mulberry), a species closely related to Morus alba.4*


*Some botanists have suggested that these two species are actually one and the same, but this remains a controversial question that can be answered only by more refined studies.5


The Indian researchers studied the effects of mulberry on blood glucose levels, on blood lipid levels (cholesterol and triglycerides), and on lipid peroxidation in the cell membranes of erythrocytes (red blood cells). Their test subjects were 24 men, aged 40 to 60, with mild type 2 diabetes. The men were randomized to two groups: one group received two 500-mg capsules of powdered mulberry leaves three times daily, for a total of 3000 mg (3 g) daily, while the other group received a standard treatment with glibenclamide (more commonly called glyburide), an antidiabetic drug of the sulfonylurea type. The trial lasted for 4 weeks.


Mulberry significantly reduced fasting
blood glucose levels in the diabetic
men, indicating that it could be
useful for controlling diabetes. It also
lowered the men’s cholesterol levels.


The results showed that, compared with glibenclamide, mulberry significantly reduced fasting blood glucose levels in the diabetic men, indicating that it could be useful for controlling diabetes. Mulberry also significantly lowered the patients’ total cholesterol, LDL-cholesterol, and triglycerides, while significantly increasing their HDL-cholesterol (high-density lipoprotein, the “good cholesterol”). By contrast, glibenclamide’s only significant effect was to lower triglycerides.

Mulberry Protects Blood-Cell Membranes

The researchers were interested in the patients’ erythrocyte membranes because these delicate structures, consisting primarily of lipids (fatty substances, including cholesterol), are subject to peroxidation, a destructive process brought about by the highly reactive molecular species known as free radicals. Such oxidative stress is normally offset by the presence of antioxidants, but the levels of these vital protective compounds are typically below normal in diabetic patients, as mentioned above. The resulting damage to the patients’ erythrocyte membranes can compromise their health in various ways—all part of the scourge of diabetes, in which excessive lipid peroxidation and its destructive effects are characteristic features.


© Copr. Dysprosia.
All Rights Reserved.
It turned out that mulberry significantly reduced lipid peroxidation in the patients’ erythrocyte membranes, whereas glibenclamide did not. Mulberry also brought about significant reductions in the levels of lipid peroxides in the patients blood plasma and urine. The authors stated:
In conclusion, the present study provides preliminary data that suggest that mulberry therapy is capable of enhancing glycemic control in patients with type 2 diabetes. Our work suggests that serum and erythrocyte membrane lipids of diabetic patients were favorably affected by mulberry therapy.

Mulberry Suppresses The Effect of Sucrose

In a new study, the effective ratio of extract from the leaves of mulberry (Morus Alba) to sucrose used in the preparation of confections has been found to help suppress elevated postprandial blood glucose and insulin levels.6 The efficacy of mulberry confections, with the optimally effective ratio determined, using healthy human subjects (10 healthy females, 22.3 years, and an average BMI of 21.4 kg/m2) participating in this within-subject, repeated measures study, had beneficial conclusions. Confections with 30g of sucrose and 1.2 or 3.0 g of mulberry extract were found to have suppressive effects on postprandial blood glucose and insulin.

Dance for Your Life!

Diabetes is one of the worst, yet one of the most easily preventable, of the chronic degenerative diseases that afflict us as we get older—and it’s becoming pandemic. Because of our self-indulgent lifestyle—too much rich food, too little exercise—we tend to be overweight, out of shape, and prone to high cholesterol and high blood pressure. That’s a recipe for insulin resistance and then full-blown diabetes, which opens a Pandora’s box of awful consequences.

The solution is obvious. Not so obvious, however, is the fact that there are nutritional supplements, such as mulberry, that can help us fend off diabetes while we strive to follow a healthier lifestyle. Among the many forms that such striving can take is dancing, which is probably the most enjoyable way to exercise ever invented (“the vertical expression of a horizontal desire,” as George Bernard Shaw put it). So get out there and dance! And if you should happen upon a mulberry tree … well, you’ll know what to do.

References

  1. Doi K, Kojima T, Makino M, Kimura Y, Fujimoto Y. Studies on the constituents of the leaves of Morus alba L. Chem Pharm Bull 2001;49(2):151-3.
  2. Doi K, Kojima T, Fujimoto Y. Mulberry leaf extract inhibits the oxidative modification of rabbit and human low-density lipoprotein. Biol Pharm Bull 2000;23(9):1066-71.
  3. Miyahara C, Miyazawa M, Satoh S, Sakai A, Mizusaki S. Inhibitory effects of mulberry leaf extract on postprandial hyperglycemia in normal rats. J Nutr Sci Vitaminol 2004;50;161-4.
  4. Andallu B, Suryakantham V, Srikanthi BL, Reddy GK. Effect of mulberry (Morus indica L.) therapy on plasma and erythrocyte membrane lipids in patients with type 2 diabetes. Clin Chim Acta 2001;314:47-53.
  5. Vijayan K, Srivastava PP, Awasthi AK. Analysis of phylogenetic relationship among five mulberry (Morus) species using molecular markers. Genome 2004;47:439-48.
  6. Nakamura M, Nakamura S, Oku T. Suppressive response of confections containing the extractive from leaves of Morus Alba on postprandial blood glucose and insulin in healthy human subjects. Nutr Metab (Lond) 2009 Jul 14;6(1):29.

References

  1. Cao H, Urban JF Jr, Anderson RA. Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. J Nutr 2008 May;138(5):833-40.
  2. Qin B, Dawson H, Polansky MM, Anderson RA. Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes. Horm Metab Res 2009 Jul;41(7):516-22.
  3. Khan A, Bryden NA, Polansky MM, Anderson RA. Insulin potentiating factor and chromium content of selected foods and spices. Biol Trace Elem Res 1990;24:183-8.
  4. Jarvill-Taylor JK, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr 2001 Aug;20(4):327-36.
  5. Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro. J Agric Food Chem 2000;48:849-52.
  6. Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats. Diabetes Res Clin Pract 2003;62:139-48.
  7. Preuss HG, Echard B, Polansky MM, Anderson R. Whole cinnamon and aqueous extracts ameliorate sucrose-induced blood pressure elevations in spontaneously hypertensive rats. J Am Coll Nutr 2006;25:144-50.
  8. Kern W, Peters A, Fruehwald-Schultes B, et al. Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 2001;74:270-80.
  9. Stahl A, Evans JG, Pattel S, Hirsch D, Lodish HF. Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes. Devel Cell 2002 Apr;2:477-88.
  10. Khan A, Safdar M, Khan MMA, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003 Dec;26(12):3215–8.
  11. Wang JG, Anderson RA, Graham GM III, Chu MC, Sauer MV, Guarnaccia MM, Lobo RA. The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study. Fertil Steril 2007;88(1):240-3.
  12. Anderson RA. Chromium and polyphenols from cinnamon improve insulin sensitivity. Proc Nutr Soc 2008;67:48-53.
  13. Solomon TPJ, Blannin AK. Effects of short-term cinnamon ingestion on in vivo glucose tolerance. Diabetes Obes Metab 2007;9(6):895-901.
  14. Sheng X, Zhang Y, Gong Z, Huang C, Zang YQ. Improved insulin resistance and lipid metabolism by cinnamon extract through activation of peroxisome proliferator-activated receptors. PPAR Res 2008;2008:581348. Epub 2008 Dec 11.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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