Adding to the benefits of an important
herbal supplement …
Cinnamon Improves Oxygen
Transport and Blood Pressure
By reducing glycated hemoglobin,
along with systolic and diastolic levels
By Will Block
n a new clinical trial—the first of its kind conducted in the United Kingdom—researchers report that a 2 g serving of cinnamon taken orally each day for 12 weeks achieved beneficial effects on glycated hemoglobin (HbA1c) and blood pressure in poorly controlled type 2 diabetes. That’s good news for diabetics (and probably for borderline diabetics, as well as those who are overweight, obese, or insulin-resistant). Everyone knows someone who fits that bill.
HbA1c and the Concept of AGEs
In the early years of life, HbA1cs are usually minor components of human hemoglobin, but as we age this tends to change. Produced in a non-enzymatic glycation pathway by hemoglobin’s exposure to plasma glucose, the subfraction HbA1c was identified by Iranian-born scientist Dr. Samuel Rahbar in the 1960s as a disabled molecule that increases in diabetes. This finding later turned out to be an important marker with clinical applications. The measurement of HbA1c in diabetic patients has become an established procedure for evaluating long-term control of diabetes, and since this measurement was first introduced, the quality of care of diabetic patients has improved significantly.
The measurement of HbA1c in diabetic
patients has become an established
procedure for evaluating long-term
control of diabetes.
Importantly, HbA1c is the first example of in vivo nonenzymatic glycation of proteins, and its discovery opened new avenues of research on Maillard reactions in biological systems. Glycation is the first step in Maillard reactions. Among the new research prospects are the concept of advanced glycation/lipoxidation end products (AGEs/ALEs) and the development of diabetic complications and various diseases associated with aging. (See
“AGE-Reducing Nutrients Could Save Your Kidneys” in the August 2010 issue and
“Preserve and Protect Your Hemoglobin” in the November 2009 issue.)
Less Oxygen Delivered; Less CO2 Expelled
Once hemoglobin is glycated, it loses its ability to transport oxygen from your lungs through the bloodstream to the rest of your body. Moreover, it also loses its ability to collect carbon dioxide for return to your lungs, where it is expelled from your body. This occurs in everyone. However, as the average amount of plasma glucose increases, and individuals move toward diabetes, the fraction of HbA1c increases in a predictable way. In type 2 diabetes, higher amounts of HbA1c indicate poorer control of blood glucose levels, and elevated levels are associated with cardiovascular disease, nephropathy, and retinopathy. All of these are incremental diseases, which take a long time to reach full-blown morbidity and herald increased mortality. A recent University of Cambridge review reported that a 1% increase in absolute concentrations of HbA1c is associated with about 10–20% increase in cardiovascular disease risk.
(transporting oxygen throughout the body)
Once hemoglobin is glycated, it loses
its ability to transport oxygen from
your lungs through the bloodstream
to the rest of your body.
Of principal interest, the accumulation of AGEs has been implicated in several pathologies associated with aging and diabetes. For example, the formation of AGEs is accelerated in hyperglycemia, which alters the structure and function of long-lived proteins such as hemoglobin.
(impeded by glucose and hemoglobin glomming together)
Cinnamon Rescues Hemoglobin
Thus, inhibition of the formation of AGEs is believed to play a role in the prevention of diabetic complications. In evaluating the antiglycating effect of aqueous extracts of various plant-based foods, cinnamon was prominent among ginger, cumin, black pepper and green tea, which inhibited in vitro AGEs.
Just last year, the Diabetes Association Standards of Medical Care in Diabetes added the criteria of HbA1c ≥ 6.5% as another diagnosis of diabetes. In the UK study, treatment with cinnamon lowered the mean HbA1c from 8.22% to 7.86%, a significant decline.
Systolic and Diastolic Blood Pressure Measurements Normalized
At the same time, the study found that the regimen of cinnamon reduced both systolic and diastolic blood pressure in type 2 diabetes from 132.6 to 129.2 mmHg and 85.2 to 80.2 mmHg, respectively. These declines were also significant. According to the current guidelines for the treatment of diabetes, normal or near normal blood pressure with a systolic blood pressure of < 130 mmHg and a diastolic blood pressure of < 80 mmHg should be achieved. This is exactly what cinnamon was able to do in most of the subjects in the study.
It is remarkable to report that
cinnamon adjunctively improved both
HbA1c and blood pressure in poorly
controlled diabetics who were also
taking conventional drugs to lower
these medical risk factors.
Over the study’s course, those with elevated baseline blood pressure (~134/86 mmHg) demonstrated improvements in systolic blood pressure and diastolic blood pressure with the addition of cinnamon. This suggests that subjects with a higher baseline blood pressure level may benefit more from cinnamon intake. Also, the achievement of better glycemic control may improve blood pressure as findings from another study have demonstrated. In this study, the effect of cinnamon on blood pressure was greater especially for those who, at baseline, had higher systolic blood pressure measurements.
Beyond the Benefits of Conventional Drugs
Participants in this study had also been treated with
metformin and sulphonylurea—medications that have different pharmacological effects—both before and during the study. Twenty-four of the 30 subjects in the cinnamon arm were taking the glucose-lowering medication metformin, while 2 were taking the insulin release increasing medication sulphonylurea, and 4 were taking both. In the placebo arm, the numbers were similar. It is remarkable to report that cinnamon adjunctively improved both HbA1c and blood pressure in poorly controlled diabetics who were also taking conventional drugs to lower these medical risk factors.
The Independence of Cinnamon
The results of studies in animals have indicated that cinnamon may also regulate blood pressure levels through peripheral vasodilatation. However, the exact blood pressure-lowering mechanism of cinnamon is still unknown and new studies are needed to clarify this issue. None of the previous human trials reported a beneficial effect of cinnamon on blood pressure.
Cinnamon throws a life saver to oxygen carriers.
After adjusting for quantitative predictors, it was demonstrated in the UK study that there were no possible influences from body weight change, HbA1c, total energy intake, or sodium intake on changes in systolic and diastolic blood pressures. When evaluating the effect of sodium on systolic and diastolic blood pressures separately, the intake of low or high sodium did not significantly change the study’s results in either group. Consequently, the researchers concluded that cinnamon is independently associated with blood pressure levels.
Nor were there any significant changes regarding the lipid profiles between the groups at baseline and post-intervention. Normally, insulin resistance results in the overproduction of very low density lipoproteins and the reduction of lipoprotein lipase activity. The consequence is dyslipidemia. Thus, the significant decrease in HbA1c might be enough to induce an improvement in the serum lipid profiles but this was found to be minimal in the study.
Up until now, there have been several suggested mechanisms of cinnamon’s action, These include delayed gastric emptying, increased glycogen synthesis by activating glycogen synthase, and inhibiting glycogen synthase kinase 3b. But none offer a clear understanding.
Berberine Moderates Glucose and Lipid
Metabolism through Multipathway Mechanism
Prior studies have shown that berberine can improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. (See
“Take This Dye for Diabetes” in the November 2010 issue). In a new paper, researchers explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin in diabetes-prone mice in which they investigated its possible glucose and lipid-regulating mechanism.
Divided into two groups, one half received berberine at 250 mg/kg/d, but the other did not. Fasting blood glucose (FBG), weight, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and fasting serum insulin were measured in both groups. The oral glucose tolerance test was performed, along with array gene expression analysis.
The blossoms of the Oregon-grape (Mahonia aquifolium, not a true grape), the official state flower of Oregon. The root of this plant is a good source of berberine, used by herbalists as a substitute for the endangered goldenseal.
Among the findings, berberine was found to significantly decrease FBG, the area under the curve, fasting serum insulin, the homeostasis model assessment insulin resistance index, TC, and TG, compared with those of control group.
The array analysis showed that berberine upregulated the expression of glucose transporter 4, mitogen-activated protein kinase 14, peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 2 (UCP2), and hepatic nuclear factor 4α(HNF4α). Downregulated were the expressions of PPARγ, CCAAT/enhancer-binding protein (CEBP), PPARγ coactivator-1α (PGC-1α), and resistin. Whew!
When taken all together, berberine moderates glucose and lipid metabolism through a multipathway
mechanism that includes the PPARα pathway among others.
- Zhang Q, Xiao X, Feng K, Wang T, Li W, Yuan T, Sun X, Sun Q, Xiang H, Wang H. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism. Evid Based Complement Alternat Med 2011;2011. pii: 924851. Epub 2010 Sep 26.
Measure Your Own Glycated Hemoglobin
Because of the role that glycated hemoglobin (HbA1c) plays in monitoring diabetes, researchers at the John Muir Physician Network Clinical Research Center in Concord, California recently decided to evaluate the effectiveness of the A1CNow SELFCHECK device when used by lay users and health care professionals to measure HbA1c.
To check the accuracy of the A1CNow SELFCHECK, 110 subjects with and without diabetes twice performed finger-stick self-tests followed by a finger-stick test of the subject’s blood by a healthcare professional. In the later instance, for accuracy comparison, a venous blood sample was drawn from each subject and tested by laboratory analysis. Out of 177 values collected A1C values, 165 (93.2%) were within the acceptable range of laboratory reference value and considered accurate.
Subjects with diabetes/prediabetes overwhelmingly indicated that they were “very” to “extremely” likely (93.5%) to discuss their home A1C results with their healthcare professional. Furthermore, lay users found the A1CNow SELFCHECK easy to use, and both lay users and healthcare professionals were able to measure A1C accurately.
Just a one-point reduction in your HbA1c reduces your risk of serious complications by 40%. Interestingly, the biofeedback nature of such a device may help lower levels as well.
- Chang A, Frank J, Knaebel J, Fullam J, Pardo S, Simmons DA. Evaluation of an over-the-counter glycated hemoglobin (A1C) test kit. J Diabetes Sci Technol 2010;4(6):1504-6.
Returning to the UK study, the baseline HbA1c percentage showed that subjects had raised glycemic levels, leading to the suspicion that the therapeutic effect of cinnamon may depend upon the subjects’ baseline HbA1c level. That is, it might be more effective in patients with elevated HbA1c. Previous human intervention trials demonstrate that in well-controlled type 2 diabetic patients where HbA1c is less than 7%, the effects of cinnamon on HbA1c may be minimalized.
The Sustainability of Cinnamon
The UK study was designed based on the minimal required duration of HbA1c change and on previous studies. What is the sustainability of the effects of cinnamon beyond the 12 weeks of the study? Other studies have left this question unanswered. Ziegenfuss et al. reported an 8.4% reduction in fasting plasma glucose in subjects with mean baseline fasting plasma glucose of 6.46 mmol/l treated with 10 g of cinnamon daily for 12 weeks.
A number of studies have found that
certain components of cinnamon—
particularly the water-soluble
polyphenol type-A polymers
extractable from this spice—
are most effective.
This illustrates that an even higher cinnamon dose can bring about a significant reduction in blood glucose in subjects with lower baseline fasting plasma glucose and suggests a possible relationship between baseline fasting plasma glucose, the dose of cinnamon, and a reduction in glycemic levels. However, the tolerability and compliance of a high dose of cinnamon along with glucose-lowering medication is uncertain and needs to be investigated further. Therefore, it remains unclear whether the effects of cinnamon are because of the dosage or the duration of the study, or because the effects are related to the baseline glycemic levels, and further studies are important to address these issues.
The treatment with cinnamon
(2 g/day for 12 weeks), along with
regular medications for type 2
diabetes, significantly reduced HbA1c
along with systolic and diastolic
blood pressure levels.
There were no changes regarding the total energy intake (calories from macronutrients and sodium) after the intervention, compared with baseline in both groups. This may be because all participants received diet and lifestyle advice from dieticians at least twice during the study period. The excellent acceptability and tolerability of cinnamon, along with a minimum dropout rate, were principal strengths in this study.
The Right Components of Cinnamon
Despite the strong points of this randomized controlled trial study design, there are some important limitations that may jeopardize its internal and external validity. Subjects were not stratified by age, gender, type of glucose-lowering medication, or time since diagnosis of diabetes. Also, participants in this study were treated with sulphonylurea and metformin. Consequently, separating the subjects based on the type of drugs they used might clarify certain issues in future studies. Although Cinnamomum cassia species was administered in this study, the precise consideration of the purity of cinnamon, the chemical composition or active ingredients, and the potency of derivatives of cinnamon may be influenced by the age of the cinnamon plant, the geographical location, the season of harvest, the method of drying and the crude preparation. A number of studies have found that certain components of cinnamon—particularly the water-soluble polyphenol type-A polymers extractable from this spice—are most effective.
Consumed for a Very Long Time
In summary, the treatment with cinnamon (2 g/day for 12 weeks), along with regular medications for type 2 diabetes, significantly reduced HbA1c along with systolic and diastolic blood pressure levels, compared to a placebo group. The dose of cinnamon was safe and well tolerated over the 12 weeks of treatment. While sustainability and durability of cinnamon have not been tested, nor has its long-term tolerability and safety—both of which will need to be determined—cinnamon has been consumed at high levels in some diets for a very long time. Nonetheless, the short-term benefits from cinnamon use in those with type 2 diabetes is evident.
- Akilen R, Tsiami A, Devendra D, Robinson N. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Diabet Med 2010 Oct;27(10):1159-67.
- Rahbar S. The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems. Ann NY Acad Sci 2005 Jun;1043:9-19.
- Saraswat M, Reddy PY, Muthenna P, Reddy GB. Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications. Br J Nutr 2009 Jun;101(11):1714-21.
- Khaw KT, Wareham N. Glycated hemoglobin as a marker of cardiovascular risk. Curr Opin Lipidol 2006 Dec;17(6):637-43.
- Executive Summary: Standards of Medical Care in Diabetes—2010: Current criteria for the diagnosis of diabetes. Diabetes Care January 2010 33:S4-S10.
- Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. J Int Soc Sports Nutr 2006;3:45–53.
- 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;25:144–150.
Will Block is the publisher and editorial director of Life Enhancement magazine.