Here we go round the mulberry bush (losing as we go) …

A Newly Rediscovered
Anti-Obesity Supplement

A recent paper shows that mulberry-fruit water extracts
can produce anti-obesity effects.
By Will Block

W

hen I was a kid, my friends and I used to pass two robust mulberry bushes on the downhill terraces along our way to play in Vailsburg Park, located in Irvington, NJ where I grew up. They’re still there from the looks of Street View in Google Maps, but they are no longer bushes. Rather, they are now big trees of perhaps 40–50 feet in height. Nevertheless, back in 1952 the mulberries were very tasty, yet difficult to reach … and so delicate that they often were pulped in our hands. So one day I decided to bring a sheet along which I draped in a circle around the base of one bush. Upon shaking the branches, an abundance of mulberries dropped onto the sheet, which when lifted by its edges concentrated the delicious berries into an easy gather. That was a feast not to be forgotten. And my Mom never let me forget either, because the sheet was never white again.

What Was Not a Concern is Now a Concern

In the 1950’s I wasn’t concerned about being overweight, let alone obese, but now I struggle to maintain a desirable weight, and everywhere I turn there is another obese person. As you know, obesity plays a critical role in dyslipidemia and related disorders. Indeed, overweight and obesity is a lifestyle precipitant for type 2 diabetes, to which both my father and my mother’s father succumbed. So I was more than delighted to read a recent paper showing that mulberry water extract (MWE) from the fruit—which contain polyphenols, including gallic acid, chlorogenic acid, rutin, and anthocyanins—can produce antiobesity effects.1

Do Not Wait to Be Thirsty

White mulberry, the fruit of Morus alba L., has been used traditionally in China as a medicine for many thousands of years. Its first non-medical use was as a food for silkworms around 2700 BCE. In The Compendium of Materia Medica,2 the epic volumes written during the Ming Dynasty in the 1500’s, renowned traditional Chinese medicine practitioner Li Shizhen recommended the leaves of the white mulberry (called Sang Ye in Chinese), and possibly the fruit, for treatment of coughs, yellow phlegm, diabetes, high blood pressure reduction, cardiovascular disease prevention, antifever diuretics, liver protection, and obesity. Li also emphasized preventative medicine, in keeping with an earlier classic The Su Wen of the Huangdi Neijing, in which it was written, “To cure disease is like waiting until one is thirsty before digging a well … .”3

At Last, Again

As mentioned, mulberry contains anthocyanins, watersoluble polyphenols that exhibit antioxidant and antitumor properties. As well in its composition, other types of polyphenolic acid liberated from esters and glycosidic bonds have been reported.4 And of these, many have been suggested separately to be capable of preventing obesity via their lipid-lowering effects and adipose tissue reduction, thus suppressing the occurrence of cardiovascular, metabolic, and hepatic alterations associated with obesity. But the use of mulberry fruit as an antiobesity agent has just been rediscovered.

Mulberry Fights Arterial Plaque

Research into the mechanisms of mulberry is not new. A few years ago, scientists in Japan pinpointed a number of biologically active compounds in extracts of the leaves of the white mulberry, interestingly enough, a plant that silkworms are crazy about.5 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.6 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 you are 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.


Generally speaking, if you are obese,
your risk for diabetes is high;
if you are not, it’s low.


But there are other therapeutic approaches to diabetes as well. One is through compounds that mimic the effects of insulin, such as the polymer A constituent of cinnamon (including MHCP, methylhydroxychalcone polymer). 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.7 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 given to the rats were: 0.1–0.5 g/kg of body weight, which, for a 75-kg (165-lb) human, would be 1,215 mg at the low end and 5 times that amount at the high end. (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. Extract concentrations have improved since the time of this study.

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, especially when one’s attention is turned to Washington, DC. 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.8*


* 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.9


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.


MWEs can be used to
reduce body weight, along with
serum and liver lipids.


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.

Returning to the Fruit

In the current paper (remember, the one showing anti-obesity effects), using 16 6-week-old male hamsters, researchers investigated the effects of MWE. After 12 weeks of treatment, the results were impressive: MWE lowered high-fat diet-induced body weight and visceral fat. Also, this was accompanied by hypolipidemic effects with reduced serum triglycerides, cholesterol, free fatty acid, and the low density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio. Thus, MWE decreased hepatic lipids, protecting livers from impairment.

Also, to the good, the hepatic peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase-1 (CPT-1) were increased. PPARα is a specific member of a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes, in liver, kidney, heart, muscle, fat tissue, and elsewhere. CPT-1 is a mitochondrial enzyme that is part of a family of enzymes called carnitine acyltransferases associated with the outer mitochondrial membrane. It mediates the transport of long-chain fatty acids across the membrane by binding them to carnitine.

As well, fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were reduced by MWE, indicating that MWE regulated lipogenesis and lipolysis, which exerted the anti-obese and hypolipidemic effects. Noticeably, MWE showed both efficacy and safety in vivo. MWE can be used to reduce body weight, along with serum and liver lipids.

In addition to its richness in anthocyanins, mulberry includes cyanidine-3-glucoside, cyanidine-3-rutinoside, pelargonidin-3-glucoside, and pelargonidine-3-rutinoside. In a previous report, researchers demonstrated that feeding purified anthocyanins from blueberries or strawberries reduced the body weight and body fat of rats fed with a high-fat diet.10

Human Equivalent Dose and Safety

The amounts of MWE used in the antiobesity study were: 0.5%, 1%, and 2% (of 10 g chow/day, the typical “at your pleasure” amounts for the young male hamsters). Therefore, the hamsters received either 50 mg, 100 mg, or 200 mg of MWE, and the antiobesity results were dose dependant. At the end of 10 weeks, all percentages of MWE beat the high-fat diet, with the 1 and 2% levels equaling or beating that of the control hamsters. Even the 0.5% was close. For a 75-kg (165-lb) human, the equivalent amount would be 488 mg, 975 mg, and 1950 mg, per day. Noticeably, all of the effects exerted by MWE did not cause harm or physiological burden in vivo. So there you have it. Supplementation with MWE is very likely to add significant benefits to the rest of your anti-metabolic syndrome strategy. Overall, a good bet.

References

  1. Peng CH, Liu LK, Chuang CM, Chyau CC, Huang CN, Wang CJ. Mulberry water extracts possess an anti-obesity effect and ability to inhibit hepatic lipogenesis and promote lipolysis. J Agric Food Chem 2011 Mar 23;59(6):2663-71.
  2. Li S. Compendium of Materia Medica (Bencao Gangmu). 1st ed. Beijing: Foreign Language Press; 2003.
  3. http://en.wikipedia.org/wiki/File:The_Su_Wen_of_the_Huangdi_Neijing.djvu.
  4. Zadernowski R, Naczk M, Nesterowicz J. Phenolic acid profiles in some small berries. J Agric Food Chem 2005;53:2118–24.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Vijayan K, Srivastava PP, Awasthi AK. Analysis of phylogenetic relationship among five mulberry (Morus) species using molecular markers. Genome 2004;47:439-48.
  10. Prior RL, Wu X, Gu L, Hager T, Hager A, Wilkes S, Howard L. Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet. Mol Nutr Food Res 2009 Nov;53(11):1406-18.


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

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