Can Common Blood Pressure Medications Cause Diabetes?

By Nieske Zabriskie, ND

High blood pressure, or hypertension, is a major risk factor for cardiovascular disease. In the United States, approximately one in three adults has high blood pressure, totaling an estimated 72 million people. Additionally, more than half of Americans over the age of 60 have hypertension.¹

High blood pressure can be caused by a number of factors including hormones, kidney disease, and cardiovascular disorders. Blood pressure increases due to increased force of the contraction of the heart and increased peripheral resistance in the blood vessels. As was mentioned in the previous issue of Vitamin Research News, in the renin-angiotensin system, the enzyme renin activates the hormone angiotensin-1, which is then converted to angiotensin-2 by angiotensin-converting enzyme (ACE). Angiotensin-2 increases blood pressure by increasing sodium and water retention from the kidneys and constricting the smooth muscle around the arteries. Additionally, nitric oxide is a molecule that is produced in the endothelial lining of blood vessels where it locally causes the smooth muscle surrounding the blood vessels to relax. Sufficient production of nitric oxide is required to decrease peripheral resistance of the blood vessels. Peripheral resistance can also be increased as a result of hardening of the arteries due to calcium deposits and atherosclerotic plaque formation. There is also research regarding parathyroid hypertensive factor (PHF), a substance released from the parathyroid gland that is believed to increase blood pressure by interfering with normal calcium channel activity in vascular smooth muscle cells. Elevated PHF levels correlate with hypertension, especially in low-renin, salt-sensitive patients.^2-4

There are several types of pharmaceuticals commonly prescribed to manage high blood pressure, in addition to diet and lifestyle modifications. Diuretics, or water pills, are used to flush excess fluid and sodium from the body to decrease the amount of fluid pumped by the heart. Beta-blockers are used to decrease the rate and force in which the heart pumps blood, and alpha-blockers decrease nerve impulses that constrict blood vessels. Calcium channel blockers inhibit calcium from entering the muscle cells of the heart and blood vessels, allowing blood vessels to relax. Angiotensin converting enzyme (ACE) inhibitors suppress the hormone angiotensin-2, which causes water retention and blood vessels to narrow.⁵

It is interesting that death caused by coronary artery disease and sudden death is not significantly reduced by the use of anti-hypertensive medications in hypertensive patients, despite the evidence that hypertension is a major risk factor for heart attacks.⁶ Some researchers suggest that this is due to adverse metabolic effects caused by the pharmaceuticals that counteract the benefits of lower blood pressure.⁶ For example, diuretics disrupt electrolytes causing low potassium, magnesium, and sodium, and may increase uric acid. Thiazide diuretics are also associated with a decline in kidney function.⁷ Both diuretics and beta-blockers interfere with blood glucose and lipid metabolism, and ACE inhibitors can elevate potassium.⁸

Some of the most concerning findings indicate that thiazide diuretics, considered the first-choice drug for hypertension, are associated with an increased risk of diabetes. In one study, non-diabetic subjects age 60 or older with systolic hypertension were treated with the thiazide diuretic chlorthalidone or a placebo. The results showed that this diuretic significantly decreased levels of serum potassium, known as hypokalemia, and this correlated with a significant increase in diabetes. In fact, the study showed that for each 0.5 milliequivalent-per-liter (MEq/L) decrease in serum potassium, there was a 45 percent increased risk of developing diabetes.⁹ Diabetes mellitus and hypertension each independently confer increased cardiovascular risk, and that risk is much greater when the diseases coexist.

According to the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, thiazide-type diuretics should be used as the first choice therapy for most patients with hypertension, despite the data from the large ALLHAT trial, which showed that thiazide-type diuretics cause hypokalemia, glucose intolerance, and diabetes. The study showed a significant 43-65 percent higher risk of new-onset diabetes with the diuretic chlorthalidone compared with a calcium channel blocker (30 percent) and an ACE inhibitor (18 percent). The researchers justified their recommendation to use thiazide-type diuretics as the first choice therapy for most patients with hypertension based on the data that the greater incidence of diabetes did not translate into more cardiovascular events. However, other researchers suggest that drawing such a conclusion ignores the morbidity and mortality associated with diabetes over decades, and not the short 2-6 year time frame examined in the ALLHAT study.^10-11

Another study found a similar association between anti-hypertensive drugs and diabetes. This long-term study found that 20.4 percent of hypertensive subjects treated with anti-hypertensive medications developed diabetes, and new-onset diabetes correlated with a significantly increased risk for stroke, myocardial infarction, and mortality.¹² Other studies have shown that the mean fasting glucose levels increased with thiazide-type diuretics, a calcium-channel blocker, or ACE inhibitor measured after 4.9 years,¹³ and patients with hypertension who were taking beta-blockers had a 28 percent higher risk of developing type 2 diabetes.¹⁴

In addition to diabetes, anti-hypertensive medications are associated with adversely impacting lipid profiles. Studies have shown that beta-blockers reduced the ratio of beneficial high-density lipoprotein (HDL) to total cholesterol by 11.7 percent and increased serum triglyceride levels by 25.8 percent.¹⁵ Diuretics can cause an increase in total and low-density lipoprotein (LDL) cholesterol and triglyceride levels while beta-blockers can decrease HDL cholesterol and increase triglyceride levels.¹⁶ Some beta-blockers also have been found to decrease levels of CoQ10.¹⁷

Natural Support for High Blood Pressure

Hypertension can have dangerous consequences and patients should never stop taking their blood-pressure lowering drugs without a doctor’s guidance. However, for individuals who want to explore other options, there are a number of approaches that can be taken.

Natural products have many different mechanisms to modulate blood pressure. Cordyceps and shark cartilage, as found in PRESSURE-fX™, address both the renin-angiotensin system as well as PHF. Research suggests that shark cartilage and Cordyceps are PHF antagonists. Animal models show that shark cartilage administration decreased blood pressure and modulates intracellular calcium regulation.¹⁸ Studies indicate that Cordyceps also lowers blood pressure in animal models, relaxes blood vessels, and elicits a dose-dependent relaxation of extra-cellular calcium-dependent contractions.¹⁹ Researchers believe that shark cartilage and Cordyceps may benefit both high-renin and high-PHF patients. A clinical trial with hypertensive patients showed that adding PRESSURE-fX was more effective at lowering blood pressure than diet, lifestyle modifications, and mineral supplementation alone. In fact, 88 percent of subjects had significantly reduced blood pressure, and 75 percent of subjects were able to maintain normal blood pressure without medication.²⁰

While a blend of Cordyceps and shark cartilage can be used in patients whose blood pressure issues are caused by an increase in intracellular calcium, a combination of grape seed extract, a special form of blueberry extract and vitamin K2 (as in Circutrol BP™) can often be useful in patients who are deficient in nitric oxide and who experience increased ACE activity and arterial calcification. Grape seed extract has been shown to increase platelet-derived nitric oxide production, which induces relaxation of blood vessels.^21-22 Additionally, animal models suggest that grape seed extract acts as a calcium channel blocker.²³ One clinical trial showed that 300 mg per day of grape seed extract supplemented for 8 weeks decreased systolic blood pressure by an average of 8.3 mmHg and diastolic blood pressure by 5.7 mmHg.²⁴

Research also suggests that blueberry extract acts as a potent ACE inhibitor. In one study, a diet containing 3 percent blueberry extract or a control diet was fed to spontaneously hypertensive stroke-prone rats for 8 weeks. The blood pressure of the spontaneously hypertensive stroke-prone rats was 30 percent lower on the blueberry diet than on control diet at 6 weeks. In addition, the rats on the blueberry diet showed a 48 percent lower glucose/insulin ratio compared to rats on the control diet. The researchers concluded that a 3 percent blueberry diet can delay the onset and reduce the magnitude of hypertension, and may reduce insulin resistance in these rats.²⁵ Another study fed rats a diet supplemented with blueberries and showed that the blueberry diet affects vascular smooth muscle contraction by suppressing a1-adrenergic receptor agonist-mediated contraction.²⁶

Vitamin K2 (menaquinone) can also be an important part of a blood-pressure-maintenance formula. Vitamin K2 promotes arterial elasticity by inhibiting calcification of blood vessel walls. Vitamin K is a cofactor for the Matrix Gla-Protein found in blood vessel walls that functions to inhibit vascular calcification and atherosclerosis.²⁷ Researchers have demonstrated in human studies that increased intake of vitamin K2 is associated with decreased coronary calcification.²⁸

Conclusion

Research is beginning to indicate that certain prescription anti-hypertensive agents may be associated with an increased risk of diabetes. Both Cordyceps and shark cartilage, found in PRESSURE-fX, and grape seed extract, blueberry extract, and vitamin K2, found in Circutrol BP, can help to maintain healthy blood pressure levels. Each formula has unique mechanisms to address the numerous potential causes of high blood pressure.

References

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2. Pang PK, Benishin CG, Shan J, et al. PHF: the new parathyroid hypertensive factor. Blood Press. 1994 May;3(3):148-55.

3. Lewanczuk RZ, Resnick LM, Blumenfeld JD, et al. A new circulating hypertensive factor in the plasma of essential hypertensive subjects. J Hypertens. 1990;8:105-108.

4. Pang PK, Benishin CG, Shan J, et al. Parathyroid Hypertensive Factor: A new vasoactive substance from the parathyroid gland. In “Calcium Regulating Hormones and Cardiovascular Function,” MF Crass and LV Avioloi (eds.), CRC Press Inc., Boca Raton, Florida, 111-130, 1995.

5. National Institutes of Health. How is High Blood Pressure Treated? Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/Hbp/HBP_Treatments.html. Accessed on: 02-07-09.

6. Morgan TO. Metabolic effects of various antihypertensive agents. J Cardiovasc Pharmacol. 1990;15 Suppl 5:S39-45.

7. Reungjui S, Pratipanawatr T, Johnson RJ, et al. Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia. Curr Opin Nephrol Hypertens. 2008 Sep;17(5):470-6.

8. Preuss HG, Burris JF. Adverse metabolic effects of antihypertensive drugs. Implications for treatment. Drug Saf. 1996 Jun;14(6):355-64.

9. Shafi T, Appel LJ, Miller ER 3rd, et al. Changes in serum potassium mediate thiazide-induced diabetes. Hypertension. 2008 Dec;52(6):1022-9.

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11. Aksnes TA, Reims HM, Kjeldsen SE, et al. Antihypertensive treatment and new-onset diabetes mellitus. Curr Hypertens. Rep 2005 Aug;7(4):298-303.

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13. Barzilay JI, Davis BR, Cutler JA, et al. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2006 Nov 13;166(20):2191-201.

14. Gress TW, Nieto FJ, Shahar E, et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med. 2000 Mar 30;342(13):905-12.

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16. Hunninghake DB. Effects of celiprolol and other antihypertensive agents on serum lipids and lipoproteins. Am Heart J. 1991 Feb;121(2 Pt 2):696-701.

17. Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977 May;17(1):157-64.

18. Communication with Peter Pang, Ph.D., professor emeritus, University of Alberta, December 2001.

19. Pang PK, Shan JJ, Chiu KW. The Cardiovascular Effects of Cordyceps Sinensis in Normotensive Rats. Journal of Chinese Medicine. 1996; 7(2):153-167.

20. Malina O, Malina M, Kotsifas G, et al. Treatment of Mild to Moderate Arterial Hypertension with Pressure-FX®. Unpublished research. Instituto de Medicina Ortomolecular, Parana, Brazil.

21. Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C. Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond). 2008 Feb;114(4):331-7.

22. Freedman JE, Parker C, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001;103:2792-8.

23. Zhang TX, Niu CQ, Hu JM, et al. Vasorelaxational effects of procyanidins on rabbit aorta in vitro and decreasing arterial blood pressure in vivo. Zhongguo Zhong Yao Za Zhi. 2008 Jul;33(14):1720-3.

24. Lu B, Robinson M, Kappagoda T. Effect of a Novel Grape Seed Extract on Blood Pressure in Subjects with Prehypertension. Presented at the FASEB Experimental Biology Conference, Washington, DC, April 30, 2007.

25. Sweeney M, Shaughnessy K, Gottschall-Pass K. Blueberry diets delay the onset of hypertension and reduce insulin resistance in spontaneously hypertensive stroke prone rats. FASEB J. 2007;21:847.

26. Norton C, Kalea AZ, Harris PD, et al. Wild Blueberry-Rich Diets Affect the Contractile Machinery of the Vascular Smooth Muscle in the Sprague–Dawley Rat. J Med Food. 2005 Spring;8(1):8-13.

27. Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603.

28. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2008 Jul 19. Published online ahead of print.