New Benefits from a Spice and a Metal
Using a strain of unfortunate rats, researchers find
benefits for hypertension as well as glucose control
Are you about 5 or 6 feet tall? Let’s imagine for a moment that you had shrunk to about 5 or 6 inches. How would you like being stalked by animals—cats, dogs, snakes, hawks, and others—who could eat you in a few gulps? And what about being persecuted by normal-sized, stick-wielding humans? What if, to try to avoid these huge beasts, you had to hide during the day and skulk around at night? What if you had to be constantly wary of encountering some device that would trap you or kill you? And what if you could never be sure that the food you were eating wasn’t poisoned? It all might make you a little paranoid, no? And what about your blood pressure? Do numbers go that high?
It’s not easy being a rat—and no, we’re not feeling sorry for them, just trying to get a feel for what it must be like to be one. Considering how tremendously successful rats have been in surviving and thriving on planet Earth, though, they must be doing everything right. They’re tough as nails, extremely clever and adaptable, and they breed like crazy. And somehow, despite the constant stress of their nightly lives, they have evolved with a blood pressure that doesn’t make them explode.
A Hypertensive Rat Is a Useful Rat
On the other hand, some rats do develop hypertension (high blood pressure), of unknown origin. Various strains of these so-called spontaneously hypertensive rats(SHRs)* have been bred and widely used in medical research for several decades because of the physiological features they share with humans who have hypertension of unknown origin. SHRs are available as stroke-prone and stroke-resistant substrains, among others.
*Where do you measure a rat’s blood pressure? On his tail, with a plethysmograph, a device that measures and records changes in the volume of an organ or body part.
Although SHRs are used mainly in studies pertaining to cardiovascular diseases, they have proved to be useful in many other diseases as well, especially those, such as diseases of the kidneys, eyes, brain, etc., that are caused or exacerbated by hypertension. Because these rats tend to be hyperactive, they have even found use in research pertaining to attention-deficit hyperactivity disorder (ADHD) in children.
As these unfortunate rats mature over a period of weeks, their blood pressure gradually rises to abnormal levels before stabilizing. By about 10 weeks of age, the male rats’ average systolic pressure (the higher of the two values, corresponding to the heart’s ventricular contractions) may, in a typical case, reach 200 mmHg, and over the next several weeks, it tends to level off, often in the range of about 200–225 mmHg.
Although we still don’t know why this hypertension occurs, there have been many speculations. A plausible one is that there’s an overstimulation of the sympathetic nervous system, which is known to increase blood pressure through its neurotransmitter, noradrenaline (norepinephrine in modern medical terminology).1
Why Insulin’s Job Is So Important . . .
Another of noradrenaline’s many physiological actions is to stimulate the conversion of glycogen to glucose in the liver (thus tending to raise blood glucose levels). Glycogen is a polymeric form of glucose, our body’s primary fuel molecule. When we have more than enough glucose (blood sugar) in our bloodstream to serve our cells’ energy needs at the moment, insulin facilitates the conversion of the excess glucose to glycogen, which is stored primarily in the liver and skeletal muscles. Then, when the glucose supply declines or the demand for it rises, glycogen is converted back to glucose.
But what if our blood glucose levels rise too high (hyperglycemia)? That’s a dangerous condition, especially if it becomes chronic, because in the long run, it can cause great harm to many bodily tissues and organs. If the levels rise beyond normal, it’s insulin’s job to lower them again, either by inducing the transport of glucose molecules into cells that need them or by causing them to be polymerized to glycogen for storage.
. . . And Why Failure Can Be Catastrophic
Sounds like a great system, doesn’t it? And it is—unless it starts to fail. If our cells become resistant to insulin’s glucose-transport function—a condition called insulin resistance—our pancreas responds by making more insulin to compensate for its reduced efficiency. But excessive insulin levels in our blood (hyperinsulinemia) are dangerous too, for all kinds of reasons, and insulin resistance can become progressively worse.
Thus a bad situation can be exacerbated until it spirals out of control—and then it’s type 2 diabetes, one of the major chronic degenerative diseases of mankind. Diabetes can cause grievous harm throughout the body, and it can greatly increase the risk for other serious diseases, including hypertension.
Cinnamon Mimics Insulin
You’ve noticed the pattern, haven’t you? There is some kind of relationship between hypertension and disturbances of glucose metabolism (hyperglycemia, hyperinsulinemia, insulin resistance, and diabetes). The relationship involves many hormones, electrolytes, proteins, and other chemical entities interacting with one another in complex ways, which we can’t get into here (be thankful). So let’s look at a recent study on the effects of a certain nutritional supplement on hypertension in spontaneously hypertensive rats.2
The supplement was cinnamon. The researchers chose this popular spice because prior research had established that certain water-soluble polyphenolic compounds in cinnamon, called procyanidins (type A), act as insulin mimetics, i.e., they mimic the physiological actions of insulin.3 And a clinical trial on diabetic patients had shown that cinnamon had beneficial effects on blood levels of glucose, cholesterol, and triglycerides (fats).4 (See “Cinnamon Reduces Blood Sugar and Cholesterol Levels” in the February 2004 issue.)
How Does Cinnamon Affect Sucrose-Induced Hypertension?
In the new study, the researchers evaluated the effects of cinnamon on the systolic blood pressure of spontaneously hypertensive rats whose diets contained a good deal of sucrose (cane sugar), the same kind of sugar that we humans consume in such great amounts.2 Sucrose consists of two carbohydrate units—glucose and fructose—joined by a chemical bond; in the digestive tract, it breaks down to these two simpler sugars. The added sucrose would be expected not just to increase the rats’ blood glucose levels but also to raise their blood pressure even more—a phenomenon that has been associated with increased insulin resistance.
The study utilized 116 male SHRs (of unspecified age) that were fed two diets differing only in their carbohydrate content. In the starch diet, the sole source of carbohydrates was cornstarch, representing 52% of the diet’s total caloric value. In the sucrose diet,the carbohydrate calories came from cornstarch (34%) and sucrose (18%), making 52%. Based on calories alone, therefore, the sucrose-diet rats would not be expected to gain any more weight than the starch-diet rats. The sucrose diet was designed to duplicate the average sugar content (18%) of the American diet; thus, the rats on that diet were meant to represent us.
The researchers did three experiments with these rats, described in the following three sections.
- Cinnamon Reduces Body-Weight and Blood-Pressure Gains
Over a 25-day period, the starch-diet control rats (no cinnamon supplementation) gained about 33% in weight, while the sucrose-diet control rats gained about 42%, indicating that sucrose had an effect that went well beyond calories. Adding whole cinnamon powder (8% by weight) to these two diets reduced the weight gain in the sucrose group to about the same amount as in the starch group but did not appreciably reduce the weight gain in the starch group.
Evidence suggests that cinnamon
counteracted some component(s) of
the genetic factors that caused all the
rats to be hypertensive in the first
place. That’s noteworthy.
Both control groups also experienced significant increases in systolic blood pressure: 20 mmHg in the starch group and 38 mmHg in the sucrose group. Here the 8% cinnamon supplementation had a more dramatic effect: it reduced the blood-pressure gains in both groups, to levels well below those of the control starch group; in other words, all of the rats’ blood pressures still increased significantly, but by lesser amounts than those in the control starch group. This suggests that cinnamon counteracted not only the sucrose-induced blood-pressure elevation but also some component(s) of the genetic factors that caused all the rats to be hypertensive in the first place. That’s noteworthy.
- Cinnamon’s Actions Are Dose-Dependent
In this experiment, all the rats received the sucrose diet, with different amounts of cinnamon added: 0%, 1%, 2%, 4%, and 8%. Over a 25-day period, the gains in body weight were reduced in a dose-dependent manner, with the 8% cinnamon diet providing a markedly greater reduction (and the only statistically significant one) than the rest.
Over a 28-day period, all four doses of cinnamon reduced the rats’ blood pressure, in a dose-dependent manner. Although this experiment was apparently conducted in the same way as the blood-pressure trial in the first experiment, with the same control sucrose diet and the same 8% cinnamon-supplemented diet (along with the three lesser amounts of cinnamon this time), the results here were very different. Whereas the control sucrose rats gained 38 mmHg in the first experiment, they gained only 7 mmHg in this one. And whereas the 8% cinnamon in the first experiment merely reduced the rate of increase in blood pressure, here it reduced the blood pressure (by 13 mmHg) to levels below those at the outset of the trial.
Oddly, the authors did not explain these striking anomalies in their paper, but the lead author did so through personal communication.5 He stated that different batches of SHRs can differ greatly in terms of their level of inherent hypertension and their susceptibility to the induction of further hypertension by sucrose. In this case, he said, the experiments were done months apart on different batches of rats; this naturally required separate controls for each experiment, and the results had to be interpreted accordingly.
This serves as a useful example of how difficult it can be to do good research when the basic parameters are so variable; how ambiguous or even contradictory the results can be; and, therefore, how very difficult (sometimes impossible) it can be to draw valid conclusions from them.
- Cinnamon’s Benefits Are Derived from the Water-Soluble Extract
This experiment was designed to confirm the results of previous research indicating that the biological activity of cinnamon resides mainly in its water-soluble components, not its oil-soluble components. This is important to know because cinnamon contains appreciable amounts of the anticoagulant (blood thinner) coumarin, which is oil-soluble. Ingesting too much coumarin could be harmful. This can easily be prevented, however, by taking only the water-soluble extract, which contains no coumarin.
Chromium is used as a benchmark
Along with the control starch and sucrose diets, the researchers used sucrose diets to which either whole cinnamon powder or water-soluble cinnamon extracts had been added. As an additional benchmark, they included one group of rats on a sucrose diet to which they had added the mineral chromium in the form of the organic compound chromium histidinate. Chromium plays an important role in glucose metabolism, and there is evidence that it may help prevent insulin resistance. It also has cardiovascular benefits (see “Chromium Improves Heart Function in Diabetics” in the August 2005 issue), and it may even be useful in atypical depression (see the sidebar “Chromium Proves Its Mettle” in the article “Controlling Blood Sugar with Cinnamon” in the December 2005 issue).
Cinnamon does well, chromium does better
The researchers measured body weight and systolic blood pressure as before, along with blood levels of glucose, fructosamine (a metabolite of fructose), total cholesterol, HDL-cholesterol (the “good cholesterol”), and triglycerides. Over a 4-week period, they found no significant changes in body weight in any group. As expected, the control sucrose group had elevated blood pressure (again by 7 mmHg) compared with the control starch group. All the cinnamon supplements prevented this sucrose-induced increase, maintaining the blood pressure at about the same level as that of the control starch group. Chromium histidinate, however, went a significant step further, by reducing the blood pressure another 7 mmHg, or 14 mmHg below that of the control sucrose diet.
Paradoxically, the sucrose diet caused a slight decrease in glucose levels, rather than the expected increase, and most of the cinnamon-supplemented diets increased the glucose levels; these changes were not statistically significant, however. The cinnamon extracts, but not whole cinnamon, significantly reduced the fructosamine levels, as did chromium histidinate. Total cholesterol levels were unchanged. HDL-cholesterol and triglycerides were significantly reduced only by chromium histidinate.
Water-soluble extract contains procyanidins (type A)
Overall, the results showed that there were only minor differences between whole cinnamon powder and water-soluble cinnamon extract, meaning that the latter is suitable for use as a supplement. As mentioned above, the biologically active procyanidins (type A) are water-soluble, so they are found in the extract. [Also present is a compound called MHCP (methylhydroxychalcone polymer), which until 2004 was thought to be the substance primarily responsible for cinnamon’s reported ability to regulate glucose levels.]
Diet, Exercise, Cinnamon, and Chromium
Some foods that are known to promote insulin resistance—notably fats and sugars—are also associated with an increased risk for hypertension. Underscoring this relationship between glucose metabolism and blood pressure is the fact that certain antidiabetic drugs, which suppress insulin resistance, also lower blood pressure. The same is true of the best “drug” of all, physical exercise. Thankfully, some nutritional supplements are also beneficial in this regard, and leading the way are cinnamon and chromium.
- Triantafyllidi E, Baldwin C, Schwartz F, Gavras H. Study of hypertension in spontaneous hypertensive rats by sequencing the genomic DNA of alpha2B receptors. Hellenic J Cardiol 2004;45:65-70.
- 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.
- Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, Schoene NW, Graves DJ. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem2004;52:65-70.
- Khan A, Safdar M, Khan MMA, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-8.
- Preuss HG, personal communication, April 25, 2006.
Sleep Deprivation Can Lead to Hypertension
If you fell asleep while reading the accompanying article (how could you?), perhaps you’re not getting enough sleep on a regular basis. That’s a common problem in our fast-paced society, and it comes with plenty of baggage. For one thing—and it’s a bigthing—sleep deprivation is associated with cardiovascular disease. Your heart, after all, is your most important muscle, and, although it can’t rest in the same way as your other muscles, it does need you to sleep adequately so it can rest in its own way—by slowing down for a good long while and enjoying the benefits of your lowest blood pressure, whatever that may be.
A new study in the United States has shown that sleep deprivation can lead to hypertension, which is intimately associated with heart disease.1 For an 8–10-year period, researchers monitored the sleep habits and blood pressure of 4810 adults who, at baseline, were 32–86 years old and were not hypertensive. After adjusting for many demographic, health, and lifestyle factors, including obesity and diabetes, that might affect the outcome, the researchers found that the people who slept 5 hours or less per night were 32% more likely to develop hypertension than those who slept 7–8 hours per night.
That was for the entire population studied. When they analyzed the data for different age groups, however, they found that the effect was age-related—but not in the way one might expect. For once, older people fared better than younger ones! In the age group 32–59, the risk was 60% greater, whereas in the age group 60–86, there was no increase in risk; in fact, the risk was reduced by 15% (this was not considered to be statistically significant, however). On the other hand, sleeping too much per night (9 hours or more) increased the older group’s risk by 31%, whereas it reduced the younger group’s risk by 8%.
The authors speculated that chronic sleep deprivation could lead to the development and maintenance of hypertension through excessively prolonged exposure to typical daytime heart rate and blood pressure, elevated levels of activity of the noradrenaline-mediated sympathetic nervous system, and physical and psychosocial stressors. These factors could, in other words, condition the cardiovascular system to maintain a higher level of blood pressure than it would if it had the chance to rest adequately at night. That’s a bad kind of conditioning!
The authors also discussed a variety of possible [yawn] explanations for the … different relationships found in the younger [yawn] and older groups of … indivi … zzz …
- Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, Rundle AG, Zammit GK, Malaspina D. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. Hypertension 2006;47:1-7.