Life Extension Magazine February 2013
Breakthrough in Protecting Arteries Against After-Meal Glucose Spikes
By Richard Mayer
Did you know that your risk of suffering from cardiovascular death is the greatest in the two-hour time period after you eat a meal? That’s partly because during that time, you can experience dangerous blood sugar spikes that acutely impair blood flow through vital arteries, ultimately leading to a heart attack or stroke.
And while you may not entirely eliminate these after-meal blood sugar surges, you can build up your body’s defenses against those spikes to protect your cardiovascular system.
In a study that may represent a breakthrough in the prevention of heart attack, the proper intake of gamma tocopherol was shown to limit the artery damaging impact of an after-meal glucose burst.
This human study, published in July 2012, showed an expected 30-44% decrease in endothelial function (as measured by arterial blood flow) in men after consuming 2.5 ounces of pure glucose. Men who took gamma tocopherol five days before the glucose challenge, however, showed no significant loss of endothelial function.1
This well-designed study showed how gamma tocopherol, functioning via several proven pathways, prepared the arterial endothelium to cope with the attack of after-meal glucose.
Foundation members have supplemented with gamma tocopherol since as early as 1996.This article describes the ways gamma tocopherol builds strong countermeasures into blood vessels, preparing them to survive and thrive even after a substantial spike in blood sugar.2
After-Meal Blood Sugar Spikes Increases Heart Attack Risk
When your heart muscle calls for more blood to sustain a strong pumping action, it needs it now. Under normal circumstances, the coronary arteries—those vessels that provide blood to the heart muscle—respond by dilating and increasing blood flow accordingly. When that response fails, heart muscle cells can begin to die within minutes.3
The after-meal blood sugar surge directly impairs your arteries’ ability to respond to that immediate demand for increased blood flow.4,5 That’s one of the reasons why diabetics have such a high rate of heart attacks and other cardiovascular disorders.6
But even if you don’t have diabetes, a “normal” fasting blood sugar measurement does not protect you against the harmful effects of the after-meal spike in blood glucose.4,5,7,8 Studies show that the risk of cardiovascular death increases in the two-hour time period after you eat a meal, when blood sugar exceeds just 90 mg/dL—a number well below the definition of diabetes.9
People who have normal fasting glucose but who fail a glucose tolerance test (blood sugar measured 2 hours after a test “meal” of glucose) are said to have “impaired glucose tolerance.” Their risk for cardiovascular disease raises sharply, the direct consequence of their arteries’ inability to dilate appropriately.3,9,10
In fact, many studies now show that the 2-hour glucose tolerance test is a more telling predictor of heart attacks than the much-touted fasting glucose test.11
How After-Meal Sugar Impacts Your Cardiovascular Risk
Your risk for heart attacks, strokes, and other forms of cardiovascular disease rises dramatically when your after-meal glucose spikes.
One study showed that people who have elevated after-meal glucose levels have a 40% higher risk for cardiovascular disease in general, and a 56% greater risk for coronary artery disease, compared with normal levels.7
Another study found that men with the highest after-lunch blood sugar levels were more than twice as likely to have a “cardiovascular event” compared with those who had the lowest levels. In women that figure rose to an ominous 4.5-fold increase.11
In a study of non-diabetic people with metabolic syndrome, each increase in after-meal blood sugar of 18 mg/dL raised the risk of cardiovascular death by 26%.12
How does the after-meal burst of glucose cause such devastation?
Glucose has a powerful oxidizing effect on the arterial lining (the endothelium) that governs blood flow through the arteries.4,13 Oxidation products interfere with the production and bioavailability of nitric oxide, the signaling molecule that triggers arteries to dilate or constrict in response to changes in demand for blood flow.14-18
Worse, oxidation speeds the destruction of existing nitric oxide molecules, further impairing the endothelium’s ability to regulate blood flow in major arteries, including the coronaries.19
Together, these effects mean that a surge in blood sugar rapidly impairs your arteries’ ability to respond to your heart muscle’s immediate needs for more blood flow.14 To make matters worse, glucose surges raise levels of “adhesion molecules” that make both arteries and platelets “stickier,” increasing the risk of a fatal clot in a coronary artery.20
The stakes couldn’t be higher: Failure to protect your arteries from glucose spikes will starve your heart of blood flow, resulting, at best in an attack of angina, and at worst in a fatal heart attack.
You can’t completely avoid the spike in glucose that occurs after you eat. However, you can prepare your endothelial cells to cope with the after-meal surges in blood sugar with gamma tocopherol.
Unique Property of Gamma Tocopherol
Alpha tocopherol is the form of vitamin E used most commonly in commercial supplements. However, studies indicate that it’s the gamma tocopherol form of vitamin E that is more ideally suited for protecting your heart from after-meal glucose surges.
Studies show that levels of gamma tocopherol are a better predictor of lower heart attack risk than alpha tocopherol. 21-25 Gamma tocopherol is a superior antioxidant that traps reactive oxygen species, reactive nitrogen species, and other dangerous molecules triggered by the after-meal glucose burst.21,22,26,27 If these dangerous molecules go unopposed, they attack fats in your artery linings, depressing nitric oxide levels and promoting atherosclerosis.28,29
Gamma tocopherol also provides anti-inflammatory effects that fights atherosclerosis induced by elevated after-meal glucose spikes.27,28,30-33 Gamma tocopherol is converted in your body to gamma-CEHC, a metabolite that helps shed excessive sodium; that’s a potential benefit for those whose mealtime sodium intake is higher than desirable.21,22,26
Finally, compared with alpha tocopherol, gamma tocopherol appears to be more readily absorbed into endothelial cells, where it can exert its antioxidant effects to protect endothelial health.34
Unfortunately, studies show that high intakes of alpha tocopherol suppress blood and tissue levels of the more important gamma tocopherol. This finding explains some of the apparently contradictory findings in studies done on vitamin E supplementation (see the SIDEBAR for other factors). 21,35,36
Taken together, these factors led researchers at the University of Connecticut to explore the effects of gamma tocopherol on preventing the decline in endothelial function that accompanies the after-meal sugar spike. Let’s now examine their findings.
Gamma Tocopherol Protects against Blood Sugar Surges
In the year 2000, a study was published demonstrating that:
- After-meal blood sugar spikes in non-diabetic patients cause an immediate decline in endothelial function, and
- A combination of antioxidant vitamins could reverse that decline.8
This information remained dormant for more than a decade—until researchers in Connecticut and Korea rediscovered and amplified the findings.
These scientists had already discovered that an after-meal glucose surge raised the levels of methyl-glyoxal, a destructive byproduct of glucose metabolism that’s increased by oxidant stress.2
Suspecting that a powerful antioxidant such as gamma tocopherol could reduce the production of methyl-glyoxal following a glucose challenge, they supplemented 12 healthy young men with 500 mg/day of gamma tocopherol.2 As expected, methyl-glyoxal levels skyrocketed in the unsupplemented group following the glucose challenge.
Those supplemented with gamma tocopherol, on the other hand, had completely eliminated the rise of methyl-glyoxal, while markers of total antioxidant capacity rose substantially.
That study clearly proved that short-term gamma tocopherol supplementation could counteract one major oxidative effect of the glucose surge. Armed with this information, the researchers turned their focus to the next major consequence of the glucose surge, namely, impaired endothelial function. They designed a study that would reveal any changes in endothelial function and nitric oxide activity that might result from gamma tocopherol supplementation.1
The Breakthrough Gamma Tocopherol Study
In this study published in July 2012, fifteen young men underwent a baseline ultrasound test to detect how well their arteries would respond to blood flow changes. Blood tests were also performed.
The men then received a 5-day supplement with a mixture containing 500 mg of gamma tocopherol, 60 mg of alpha tocopherol, and small amounts of beta- and delta tocopherols. The ultrasound blood flow test and blood work were then repeated.1
Next the subjects received 2.5 ounces of pure glucose, and their endothelial function was monitored by ultrasound regularly for 3 hours.
The findings were remarkable.
Blood levels of gamma tocopherol rose 3-fold. Levels of the active metabolite, gamma-CEHC, rose 9-fold—all without affecting alpha tocopherol levels at all.1
Following the glucose “meal,” endothelial function, as measured by enlargement of blood vessels due to increases in blood flow, declined 30-44% in the unsupplemented state. But with supplementation, there was no significant loss of endothelial function.1
Supplementation with gamma tocopherol suppressed the after-meal increase in fat oxidation products and the nitric oxide disruption they caused.
In short, this well-designed study showed that supplementation with 500 mg/day of gamma tocopherol along with smaller amounts of other forms of vitamin E prepared arterial endothelium to cope with the attack of after-meal glucose. Supplementation didn’t change the fact of the surge; rather, it provided endothelial cells with the defense mechanisms they needed in order to survive it.
Most Life Extension members take around 200 mg a day of gamma tocopherol. Considering the many other similar nutrients they take like pomegranate and lycopene, they may not need to take any additional gamma tocopherol. For those choosing to capitalize on the added benefits of gamma tocopherol supplementation, supplementing approximately12 hours before glucose consumption is advisable because studies show it takes 12 hours for maximal blood levels of the active metabolite gamma-CEHC to be reached.37
After you eat a meal—even a healthy meal—your arteries and their delicate endothelial linings are subject to a short but dangerous rise in blood sugar. That blood sugar surge directly impairs your ability to regulate blood flow, raising your risk for a heart attack or other cardiovascular disaster.14
You need to defend yourself against that after-meal blood sugar escalation, in order to protect your arteries and preserve their ability to deliver blood to your laboring heart muscle.
Gamma tocopherol has now been shown in a human study to block glucose-induced impairment of nitric oxide and to sustain endothelial function following a meal.1,2
Supplementation with gamma tocopherol, therefore, allows you to prepare your body for the harmful after effects of a meal.
Most Life Extension® members take over 200 mg a day of gamma tocopherol. Considering the many other similar nutrients they take like pomegranate and lycopene, they may not need to take any additional gamma tocopherol.
Since higher gamma tocopherol levels are associated with lower risk of coronary heart disease, gamma tocopherol supplementation may reduce your own risk, and restore your arteries’ natural abilities to manage the effects of deadly after-meal glucose surges.2
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Mah E, Noh SK, Ballard KD, Park HJ, Volek JS, Bruno RS. Supplementation of a gamma-tocopherol-rich mixture of tocopherols in healthy men protects against vascular endothelial dysfunction induced by postprandial hyperglycemia. J Nutr Biochem. 2012 Jul 25.
- 2. Masterjohn C, Mah E, Guo Y, Koo SI, Bruno RS. gamma-Tocopherol abolishes postprandial increases in plasma methylglyoxal following an oral dose of glucose in healthy, college-aged men. J Nutr Biochem. 2012 Mar;23(3):292-8.
- Mont MR, Carlson CG, Geisbuhler TP. Resting Ca2+ influx does not contribute to anoxia-induced cell death in adult rat cardiac myocytes. Can J Physiol Pharmacol. 2009 May;87(5):360-70.
- Ceriello A, Taboga C, Tonutti L, et al. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation. 2002 Sep 3;106(10):1211-8.
- Kawano H, Motoyama T, Hirashima O, et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999 Jul;34(1):146-54.
- Reusch JE, Wang CC. Cardiovascular disease in diabetes: Where does glucose fit in? J Clin Endocrinol Metab. 2011 Aug;96(8):2367-76. Epub 2011 May 18.
- Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001 Feb 12;161(3):397-405.
- Title LM, Cummings PM, Giddens K, Nassar BA. Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E. J Am Coll Cardiol. 2000 Dec;36(7):2185-91.
- Leiter LA, Ceriello A, Davidson JA, et al. Postprandial glucose regulation: new data and new implications. Clin Ther. 2005;27 Suppl B:S42-56.
- Shimabukuro M, Higa N, Asahi T, et al. Impaired glucose tolerance, but not impaired fasting glucose, underlies left ventricular diastolic dysfunction. Diabetes Care. 2011 Mar;34(3):686-90.
- Cavalot F, Petrelli A, Traversa M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab. 2006 Mar;91(3):813-9.
- Lin HJ, Lee BC, Ho YL, et al. Postprandial glucose improves the risk prediction of cardiovascular death beyond the metabolic syndrome in the nondiabetic population. Diabetes Care. 2009 Sep;32(9):1721-6.
- Ceriello A, Bortolotti N, Crescentini A, et al. Antioxidant defences are reduced during the oral glucose tolerance test in normal and non-insulin-dependent diabetic subjects. Eur J Clin Invest. 1998 Apr;28(4):329-33.
- Mah E, Noh SK, Ballard KD, Matos ME, Volek JS, Bruno RS. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine. J Nutr. 2011 Nov;141(11):1961-8.
- Ogita H, Liao J. Endothelial function and oxidative stress. Endothelium. 2004 Mar-Apr;11(2):123-32.
- McCarty MF. Vascular endothelium is the organ chiefly responsible for the catabolism of plasma asymmetric dimethylarginine--an explanation for the elevation of plasma ADMA in disorders characterized by endothelial dysfunction. Med Hypotheses. 2004;63(4):699-708.
- Bode-Boger SM, Scalera F, Ignarro LJ. The L-arginine paradox: Importance of the L-arginine/asymmetrical dimethylarginine ratio. Pharmacol Ther. 2007 Jun;114(3):295-306.
- Victor VM, Rocha M, Sola E, Banuls C, Garcia-Malpartida K, Hernandez-Mijares A. Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des. 2009;15(26):2988-3002.
- Rush JW, Denniss SG, Graham DA. Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. Can J Appl Physiol. 2005 Aug;30(4):442-74.
- Ceriello A, Quagliaro L, Piconi L, et al. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes. 2004 Mar;53(3):701-10.
- Jiang Q, Christen S, Shigenaga MK, Ames BN. gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr. 2001 Dec;74(6):714-22.
- Hensley K, Benaksas EJ, Bolli R, et al. New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine. Free Radic Biol Med. 2004 Jan 1;36(1):1-15.
- Kristenson M, Zieden B, Kucinskiene Z, et al. Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50. BMJ. 1997 Mar 1;314(7081):629-33.
- Kontush A, Spranger T, Reich A, Baum K, Beisiegel U. Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol. Atherosclerosis. 1999 May;144(1):117-22.
- Ruiz Rejon F, Martin-Pena G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla B. Plasma status of retinol, alpha- and gamma-tocopherols, and main carotenoids to first myocardial infarction: case control and follow-up study. Nutrition. 2002 Jan;18(1):26-31.
- Wagner KH, Kamal-Eldin A, Elmadfa I. Gamma-tocopherol--an underestimated vitamin? Ann Nutr Metab. 2004;48(3):169-88.
- Jiang Q, Lykkesfeldt J, Shigenaga MK, Shigeno ET, Christen S, Ames BN. Gamma-tocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation. Free Radic Biol Med. 2002 Dec 1;33(11):1534-42.
- Li D, Saldeen T, Mehta JL. gamma-tocopherol decreases ox-LDL-mediated activation of nuclear factor-kappaB and apoptosis in human coronary artery endothelial cells. Biochem Biophys Res Commun. 1999 May 27;259(1):157-61.
- McCarty MF. Gamma-tocopherol may promote effective no synthase function by protecting tetrahydrobiopterin from peroxynitrite. Med Hypotheses. 2007;69(6):1367-70.
- Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11494-9.
- Jiang Q, Ames BN. Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J. 2003 May;17(8):816-22.
- Devaraj S, Jialal I. Failure of vitamin E in clinical trials: is gamma-tocopherol the answer? Nutr Rev. 2005 Aug;63(8):290-3.
- Jiang Q, Moreland M, Ames BN, Yin X. A combination of aspirin and gamma-tocopherol is superior to that of aspirin and alpha-tocopherol in anti-inflammatory action and attenuation of aspirin-induced adverse effects. J Nutr Biochem. 2009 Nov;20(11):894-900.
- Tran K, Chan AC. Comparative uptake of alpha- and gamma-tocopherol by human endothelial cells. Lipids. 1992 Jan;27(1):38-41.
- Traber MG, Siddens LK, Leonard SW, et al. Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets. Free Radic Biol Med. 2005 Mar 15;38(6):773-85.
- Wolf G. How an increased intake of alpha-tocopherol can suppress the bioavailability of gamma-tocopherol. Nutr Rev. 2006 Jun;64(6):295-9.
- Radosavac D, Graf P, Polidori MC, Sies H, Stahl W. Tocopherol metabolites 2, 5, 7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2, 7, 8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC) in human serum after a single dose of natural vitamin E. Eur J Nutr. 2002 Jun;41(3):119-24.
- Dietrich M, Traber MG, Jacques PF, Cross CE, Hu Y, Block G. Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer? A review. J Am Coll Nutr. 2006 Aug;25(4):292-9.