Reduce Your Risk of Arterial Stiffness

Atherosclerosis (or hardening of the arteries) can affect any artery in the body. It is a leading cause of heart disease and stroke.^1,2

Scientists have identified an overlooked risk factor for atherosclerosis that rivals high cholesterol—arterial stiffening.^3,4

Arterial stiffening is more than just plaque formation associated with occluded arteries.

Stiffening damages fragile capillaries that nourish our organs. This loss of youthful suppleness prevents our arteries from properly regulating blood flow and pressure.³

In addition to causing high blood pressure, arterial stiffening can lead to organ damage,⁵ which we recognize as heart attacks, strokes, cognitive decline, dementia, kidney failure, and a host of other disorders.

Combatting loss of arterial flexibility can be as simple as incorporating two nutrients into your daily regimen.

Studies show that vitamin D and vitamin K play an essential role in slowing—and even preventing—arterial stiffening.^6-8

In this article, we’ll examine how these two nutrients work together to reduce arterial stiffening, and ultimately, the degenerative disorders associated with it.

The Dangers of Arterial Stiffness

Healthy arteries consist of multilayered walls capable of constricting (narrowing) or dilating (widening) in response to the needs of the tissues they supply.

For years, scientists have studied the artery’s innermost layer, or endothelium, in an attempt to understand atherosclerosis and cardiovascular disease. They now know the damaging roles of blood sugar, inflammation, and an array of signaling molecules in disrupting blood flow.⁹

New data show that in addition to the endothelium, the middle, muscular layer of arteries is also closely involved in the blood-flow abnormalities that produce not only cardiovascular disease and hypertension, but a host of other age-related disorders.^8,10,11

In fact, arterial stiffness has now been identified as a contributing factor to:^12-16

• Hypertension
• Heart attack
• Stroke
• Kidney disorders (including end-stage renal disease)
• Liver disorders (especially non-alcoholic fatty liver disease, or NAFLD)
• Type II diabetes
• Cognitive decline
• Cerebral white matter disease (leukoaraiosis)
• Neurodegenerative disorders (e.g., Alzheimer’s, Parkinson’s)

Arterial stiffness is also emerging as a powerful predictor of death risk in an increasing number of clinical age-related conditions.^17,18

The main immediate consequence of arterial stiffening is a steady rise in blood pressure, which contributes to destructive changes that further stiffen arteries—creating a vicious cycle.^15,18,19

Causes of Arterial Stiffening

Studies show that aging alone, as well as conditions such as type II diabetes, contribute to a steady rise in arterial stiffness. These conditions can result in high blood pressure and damage to organs throughout the body.^18,20-22

One of the main contributors to arterial stiffening is calcification. This occurs when calcium from the blood is deposited into the normally supple arterial walls, leading to literal hardening of the arteries.^10,23

Increasingly, researchers are focusing on the lifestyle and nutritional factors that contribute to arterial stiffening—and, importantly, to its prevention.^14,24,25

Two key nutrients—vitamin D and vitamin K—have shown compelling promise in this area. Both play critical roles in helping our bodies to manage calcium, which makes them essential for preventing dangerous arterial stiffening.

Putting Calcium in its Place

Nutritionists used to think of vitamin D as the calcium-and-bone vitamin, and vitamin K as the blood-clotting vitamin. More current scientific evidence suggests that both vitamins play important roles in helping our bodies properly manage calcium.

Both vitamin D and vitamin K play a crucial role in calcium metabolism. Vitamin D promotes calcium absorption from the diet while also promoting calcium deposition in bones. In this way, it helps with the continuous remodeling of bone that helps keep our skeletons strong and adaptable.

Vitamin K, on the other hand, is essential for keeping calcium out of your arteries. This is because vitamin K modifies specific proteins in arterial walls, making them resistant to binding to calcium. This process prevents arterial calcification and stiffening.²⁶

In addition to keeping calcium out of your arteries, vitamin K promotes the proper deposition of calcium into bone, and vitamin K has been promoted recently as a way to prevent osteoporosis.²⁶

It is becoming increasingly clear that we need both vitamins D and K to get our dietary calcium into bones, where it belongs, and to keep it out of arteries, where it doesn’t.

Vitamins D and K can work individually and together to keep our arteries young and supple—and to prevent the myriad disorders associated with arterial stiffening.

Vitamin D: Contributor to Arterial Suppleness

Scientists have known for years that vitamin D is essential for proper calcium absorption from the diet. Now they are beginning to recognize its role in arterial health as well.

New evidence suggests that insufficient vitamin D accelerates cardiovascular diseases and may contribute to arterial stiffening.^27-29 Similarly, low vitamin D levels are associated with high blood pressure, a major manifestation of arterial stiffening.^30,31

Unfortunately, vitamin D deficiency is all too common—a problem that may be behind arterial stiffening as well as other health problems.^32,33

Two studies have demonstrated that vitamin D supplementation is an important approach to preventing or alleviating cardiovascular disease, particularly in certain high-risk groups such as diabetics, older adults, and people with deficiencies in dietary vitamin D intake or insufficient sunlight exposure.^33,34

This approach has now been validated in multiple trials studying at-risk patients.

Clinical Trials Show Dramatic Improvements

In a study of middle-aged type II diabetics, subjects received either a placebo or 1,000 IU of vitamin D daily.³⁴ After one year, supplemented patients had a decrease in their measure of arterial stiffness known as the central aortic augmentation index. There was no improvement in the placebo group.³⁴

Another study examined adults with elevated blood pressure who were vitamin D deficient. After taking 4,000 IU of oral vitamin D3 daily for 6 months, they experienced a 12.3% reduction in arterial stiffness (as measured by augmentation index). No changes were shown in a control group receiving 400 IU/day (the standard “recommended” dose).³¹

A Danish study conducted in winter months demonstrated that 3,000 IU of vitamin D3 reduced both systolic (top number) and diastolic (bottom number) blood pressure in subjects who were vitamin D insufficient (<32 ng/mL).³⁰

Numerous subsequent studies have confirmed vitamin D’s arterial stiffness-reducing effects in both healthy and high-risk populations.^27,29,35

The preponderance of evidence shows vitamin D to be a critical factor in preventing the many disorders associated with arterial stiffening—especially those involving standard risk factors such as hypertension.

Next, we turn our attention to vitamin K, the other crucial factor in maintaining healthy arterial function well into advanced years.

Teflon for your Arteries

Vitamin K plays an important role in arterial health because of its role in managing calcium. Vitamin K is required for the activation of a biomolecule called matrix Gla-protein, which inhibits calcium from being deposited in artery walls.^23,26,36,37 Think of it like Teflon for your arteries.

Without sufficient vitamin K, matrix Gla-protein fails to become activated, resulting in calcium deposition and increased arterial stiffness.^26,36,37

Many of us don’t get vitamin K in our diets, particularly if we consume processed foods, which are nearly devoid of the vitamin.²⁶ Not surprisingly, then, studies of people who have insufficient vitamin K intake reveal increased markers of arterial stiffness, especially in older adults.³⁸

These factors put anyone without ample vitamin K intake at increased risk for arterial stiffening, particularly groups already at high cardiovascular risk, such as diabetics.

The good news is that studies in both animals and humans clearly show that supplementing with vitamin K helps prevent or reduce arterial stiffness.

Benefits of Vitamin K

In a laboratory study, diabetic rats were shown to have reductions in activated matrix Gla-protein of 36%, compared with nondiabetic controls. This led to increases in major artery calcium deposits of up to 56%, and ultimately produced a 44% increase in arterial stiffness.²³

A recent human randomized controlled clinical trial illustrated the value of oral vitamin K supplementation, using a form of vitamin K2 called menaquinone-7, or MK-7.³⁹ The study involved 244 healthy, postmenopausal women, a group whose risk for cardiovascular disease approaches that of men. Half received placebo, and the other half received vitamin K2 in the form of MK-7.³⁹

This three-year study showed that supplementation with MK-7 significantly reduced (by 50%) levels of inactive matrix Gla-protein, indicating vitamin K’s protective effect on cardiovascular health.³⁹ The results from this study showed the vitamin K (MK-7)-supplemented women had significant reductions in arterial stiffness.

As an added benefit, those with the highest stiffness at baseline experienced significant improvements in a host of other arterial health parameters related to arterial suppleness as well.

Taken together, this combination of animal and human data strongly indicates the need for ample vitamin K supplementation for all of us who are at risk for arterial stiffening and the resulting hypertension, cardiovascular disease, and premature death.

Summary

Arterial stiffening is a major contributor to cardiovascular disease risk. It occurs when arteries lose their youthful suppleness, leaving us with narrowed arteries incapable of regulating blood flow and pressure, and in turn damaging the fragile capillary beds that nourish our organs.

One of the main underlying causes of arterial stiffening is a buildup of calcium in the arteries.

Vitamins D and K are intimately involved in how our bodies manage calcium—specifically keeping it in our bones, and out of our arteries. This makes these vitamins essential for preventing arterial stiffening.

Vitamin D3 (cholecalciferol) and vitamin K2 have been shown in human clinical trials to significantly reduce arterial stiffness, thereby reducing one of the most dangerous risk factors for heart disease, stroke, neurodegenerative diseases, and a variety of other so-called “age-related” disorders.

The important role vitamins D and K play in preventing arterial stiffening make it critical for all older adults to get sufficient intakes of these important vitamins—both of which are lacking in even healthy diets.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

1. Available at: https://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis. Accessed November 4, 2017.
2. Available at: https://www.cdc.gov/chronicdisease/overview/index.htm. Accessed December 4, 2017.
3. Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol. 2016;77:1-7.
4. van Popele NM, Grobbee DE, Bots ML, et al. Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke. 2001;32(2):454-60.
5. Thorin-Trescases N, Thorin E. Lifelong Cyclic Mechanical Strain Promotes Large Elastic Artery Stiffening: Increased Pulse Pressure and Old Age-Related Organ Failure. Can J Cardiol. 2016;32(5): 624-33.
6. Levin A, Tang M, Perry T, et al. Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD. Clin J Am Soc Nephrol. 2017;12(9):1447-60.
7. Mayer O, Jr., Seidlerova J, Wohlfahrt P, et al. Synergistic effect of low K and D vitamin status on arterial stiffness in a general population. J Nutr Biochem. 2017;46:83-9.
8. Mozos I, Stoian D, Luca CT. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness. Dis Markers. 2017;2017:8784971.
9. Mozos I, Luca CT. Crosstalk between Oxidative and Nitrosative Stress and Arterial Stiffness. Curr Vasc Pharmacol. 2017;15(5): 446-56.
10. Cecelja M, Chowienczyk P. Molecular Mechanisms of Arterial Stiffening. Pulse (Basel). 2016;4(1):43-8.
11. Cho JY, Kim KH. Evaluation of Arterial Stiffness by Echocardiography: Methodological Aspects. Chonnam Med J. 2016;52(2):101-6.
12. Cardoso CR, Salles GF. Aortic Stiffness as a Surrogate Endpoint to Micro- and Macrovascular Complications in Patients with Type 2 Diabetes. Int J Mol Sci. 2016;17(12).
13. Villela-Nogueira CA, Leite NC, Cardoso CR, et al. NAFLD and Increased Aortic Stiffness: Parallel or Common Physiopathological Mechanisms? Int J Mol Sci. 2016;17(4).
14. Wang M, Norman JE, Srinivasan VJ, et al. Metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Am J Neurodegener Dis. 2016;5(5):171-7.
15. Cheng HM, Park S, Huang Q, et al. Vascular aging and hypertension: Implications for the clinical application of central blood pressure. Int J Cardiol. 2017;230:209-13.
16. Joly L. Arterial stiffness and cognitive function. Geriatr Psychol Neuropsychiatr Vieil. 2017;15(1):83-8.
17. Fortier C, Agharazii M. Arterial Stiffness Gradient. Pulse (Basel). 2016;3(3-4):159-66.
18. Gavish B, Izzo JL, Jr. Arterial Stiffness: Going a Step Beyond. Am J Hypertens. 2016.
19. Prasad K, Mishra M. Do Advanced Glycation End Products and Its Receptor Play a Role in Pathophysiology of Hypertension? Int J Angiol. 2017;26(1):1-11.
20. Shirwany NA, Zou MH. Arterial stiffness: a brief review. Acta Pharmacol Sin. 2010;31(10):1267-76.
21. Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis. 2015;238(2):370-9.
22. Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol. 2005;25(5):932-43.
23. Doyon M, Mathieu P, Moreau P. Decreased expression of gamma-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein. Cardiovasc Res. 2013;97(2):331-8.
24. LaRocca TJ, Martens CR, Seals DR. Nutrition and other lifestyle influences on arterial aging. Ageing Res Rev. 2017;39:106-19.
25. Papaioannou TG, Karatzi K, Psaltopoulou T, et al. Arterial ageing: Major nutritional and life-style effects. Ageing Res Rev. 2017;37:162-3.
26. Maresz K. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integr Med (Encinitas). 2015;14(1):34-9.
27. Al-Dujaili EA, Munir N, Iniesta RR. Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study. Ther Adv Endocrinol Metab. 2016;7(4):153-65.
28. Rodriguez AJ, Scott D, Srikanth V, et al. Effect of vitamin D supplementation on measures of arterial stiffness: a systematic review and meta-analysis of randomized controlled trials. Clin Endocrinol (Oxf). 2016;84(5):645-57.
29. Sunbul M, Cincin A, Bozbay M, et al. Arterial stiffness parameters associated with vitamin D deficiency and supplementation in patients with normal cardiac functions. Turk Kardiyol Dern Ars. 2016;44(4):281-8.
30. Larsen T, Mose FH, Bech JN, et al. Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. Am J Hypertens. 2012;25(11):1215-22.
31. Zaleski A, Panza G, Swales H, et al. High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency. Dis Markers. 2015;2015:918968.
32. Dong Y, Stallmann-Jorgensen IS, Pollock NK, et al. A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. J Clin Endocrinol Metab. 2010;95(10):4584-91.
33. McGreevy C, Barry M, Davenport C, et al. The effect of vitamin D supplementation on arterial stiffness in an elderly community-based population. J Am Soc Hypertens. 2015;9(3):176-83.
34. Breslavsky A, Frand J, Matas Z, et al. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr. 2013;32(6):970-5.
35. Forouhi NG, Menon RK, Sharp SJ, et al. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double-blind placebo-controlled trial. Diabetes Obes Metab. 2016;18(4):392-400.
36. Pivin E, Ponte B, Pruijm M, et al. Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study. Hypertension. 2015;66(1):85-92.
37. Sardana M, Vasim I, Varakantam S, et al. Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus. Am J Hypertens. 2017;30(2):196-201.
38. Vaccaro JA, Huffman FG. Phylloquinone (vitamin K(1)) intake and pulse pressure as a measure of arterial stiffness in older adults. J Nutr Gerontol Geriatr. 2013;32(3):244-57.
39. Knapen MH, Braam LA, Drummen NE, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015;113(5):1135-44.
40. Booth SL. Vitamin K: food composition and dietary intakes. Food Nutr Res. 2012;56.
41. Villines TC, Hatzigeorgiou C, Feuerstein IM, et al. Vitamin K1 intake and coronary calcification. Coron Artery Dis. 2005;16(3):199-203.
42. Poli D, Antonucci E, Lombardi A, et al. Safety and effectiveness of low dose oral vitamin K1 administration in asymptomatic out-patients on warfarin or acenocoumarol with excessive anticoagulation. Haematologica. 2003;88(2):23 7-8.
43. Shetty HG, Backhouse G, Bentley DP, et al. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. Thromb Haemost. 1992;67(1):13-5.
44. Bolton-Smith C, McMurdo ME, Paterson CR, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007;22(4):509-19.
45. Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008;283(17):11270-9.
46. Elder SJ, Haytowitz DB, Howe J, et al. Vitamin k contents of meat, dairy, and fast food in the u.s. Diet. J Agric Food Chem. 2006;54(2):463-7.
47. Komai M, Shirakawa H. [Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function]. Clin Calcium. 2007;17(11):1663-72.
48. Miki T, Nakatsuka K, Naka H, et al. Vitamin K(2) (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks in elderly women with established osteoporosis. J Bone Miner Metab. 2003;21(3):161-5.
49. Kawashima H, Nakajima Y, Matubara Y, et al. Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Jpn J Pharmacol. 1997;75(2):135-43.
50. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008;100(4):530-47.
51. Suhara Y, Murakami A, Nakagawa K, et al. Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines. Bioorg Med Chem. 2006;14(19):6601-7.
52. Chow CK. Dietary intake of menaquinones and risk of cancer incidence and mortality. Am J Clin Nutr. 2010;92(6):1533-4; author reply 4-5.
53. Sato T, Schurgers LJ, Uenishi K. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012;11:93.
54. Schurgers LJ, Teunissen KJ, Hamulyak K, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109(8):3279-83.
55. Schurgers LJ, Spronk HM, Soute BA, et al. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 2007;109(7):2823-31.
56. Harvey A, Montezano AC, Lopes RA, et al. Vascular Fibrosis in Aging and Hypertension: Molecular Mechanisms and Clinical Implications. Can J Cardiol. 2016;32(5):659-68.
57. Saji N, Toba K, Sakurai T. Cerebral Small Vessel Disease and Arterial Stiffness: Tsunami Effect in the Brain? Pulse (Basel). 2016;3(3-4):182-9.