With the inexpensive noninvasive CVProfile test for arterial elasticity, we have a useful window on the common pathway of the aging process commonly called "hardening of the arteries".

  1. Systemic contributors to this common pathway include:
    1. Oxidation
    2. Glycosylation
    3. Inflammation
  2. Age related factors
    1. Decreased mitochondrial function
    2. Decreased androgenic hormonal support
  3. Other measurable contributory factors that may overlap two or more processes include:
    1. Low coenzyme Q10 levels
    2. Elevated homocysteine, C Reactive Protein (CRP)
    3. Elevated Lipoprotein (a)[1], [2], [3]
    4. Elevated endothelin-1 levels[4]
    5. Decreased Lycopene[5]
    6. Elevated blood pressure; low Ankle/brachial Index
  1. Systemic contributors
    1. Oxidative processes are necessary for life. The broad category of antioxidants serve to minimize systemic oxidative wear and tear on cell and organ systems.
      1. Vitamin C is probably the most critical and inexpensive water soluable antioxidant. Deficiencies cause periodontal disease,[6] poor connective tissue repair,[7] and ultimately scurvy.[8], [9] Higher intake of vitamin C protects personswith hypertension from stroke due to weakened and hardened blood vessels.[10]
      2. Vitamin E – a mixed group of antioxidant compounds that are fat soluble.[11], [12], [13]
      3. Selenium is an essential micronutrient in a number of antioxidant enzyme systems, including glutathione peroxidase. Large population based longitudinal studies have found low plasma selenium levels associated with increased mortality[14] and cognitive decline in older subjects.[15]
    2. Glycosylation is the binding together of protein subunits with sugar, thereby impairing their functionality. Because we always have sugar in our blood, this process goes on throughout our lives, but it is accelerated when carbohydrate intake expands far beyond basic metabolic energy needs and basal blood sugar levels increase . It is best minimized by a combination of appropriate diet and regular physical activity. Absence of the following factors can enhance glycosylation.
      1. B complex vitamins are a group of water soluable cofactors essential for avariety of enzymatic reactions involved in repairing oxidadative damage, glycosylation and inflammation.
      2. Chromium (III) piccolinate, 200 mcg, is an essential micronutrient in the production of Glucose Tolerance Factor (GTF)[16], [17], [18]
      3. Carnosine, 1000 mg, has been shown to inhibit the glycosylation of proteins and may help to reverse that process.[19], [20], [21]
    3. Inflammation is the first step of the repair process for muscle, connective tissue or bone injury, and is thus indispensable. When the localized inflammatory process doesn't turn off as the body moves to the collagen forming stage of repair, or inflammation becomes regional or systemic as a result of autoimmune dysregulation or presence of a chronic irritant, the normal repair sequences are impaired; while the metabolic intermediary homocysteine is most certainly an endothelial irritant, CRP is more likely part of the body's response to inflammation, and not irritating in and of itself.[22]The following factors can help to reduce chronic inflammation:
      1. Vitamin D3 is necessary for calcium absorbtion and then deposition into bone. When at middle age the flux of calcium reverses from into the body and bones to out from the bones, calcium tends to silt out in soft tissues literally causing hardening of the arteries. Vitamin D3 hasanti-inflammatory effects through decrease of TNF-a and increase of IL-10,[23] and low levels of vitamin D are strongly associated with increased risk of hypertension.[24], [25], [26], [27] Vitamin D also plays a role in optimizing glucose metabolism in type-2 diabetes.[28]
      2. 5-Methyltetrahydrofolate,f[29] Vitamins B6 and 12 , and Methylating agents such asTrimethylglycine , when deficient alone or in concert slow the rate of transformation of homocysteine down, allowing it to ‘Back up' in the vascular system. Homocysteine is directly irritating to endothelial cells.[30]
      3. Omega-3 fatty acids EPA and DHA[31], [32] act as a substrate to competitively inhibit arachidonic acid metabolism, reducing Thromboxane A2 and enhancing Prostacyclin-I 2 (PGI-2), reducing the extent of the inflammatory cascade without completely blocking it as corticosteroids do.
  2. Age related factors
    1. Decreased mitochondrial function – Mitochondria are pre-cellular symbionts that joined the eucaryotic cell line hundreds of millions of years ago. They do not have the sophisticated DNA repair machinery that their eucaryotic hosts have, so they will accumulate DNA mistakes more quickly, resulting in decreased efficiency of production of their primary waste product ATP over time.
      1. Coenzyme Q10 is the chief energy transfer molecule in the mitochondria.
        Coenzyme Q10 increases the efficiency of mitochondrial energy production, decreases lipid peroxidation, and independently acts as an endothelial dependent arterial relaxant, mediated via PGI-2.[33], [34], [35], [36]
      2. L-Carnitine 2000 mg,and some of its congeners facilitate transfer of fattyacids into mitochondria for burning . The result is increased walking distance in persons with peripheral vascular disease.[37]
    2. Decreased androgen production from ovaries, testis and adrenals occurs predictably from the quarter century to the century mark, and is associated with greater arterial stiffness.[38] Hormone Replacement Therapy with isomolecular hormones is controversial, but less so than with synthetic progestogens, androgens and Premarin. In the context of decreasing hormonal support, Vitamins K1 & K2 help to maintain the flux of calcium into the bones. This diminishes the likely hood of calcium flux out of the bones silting out in soft tissues like breast and blood vessels, causing true hardening of the arteries.[39]
      1. Topical testosterone.[40], [41], [42], [43], [44], [45]
      2. Topical estrogens and progesterone.[46]
      3. DHEA, 10-50 mg.[47], [48], [49]
      4. Chrysin 500 mg, a passion flower extract that blocks conversion of testosterone to estrogenic substances; similar to the drug Arimidex.[50] These are controversial as a significant portion of the cardiac benefit is postulated to derivefrom the conversion of testosterone to 17Beta-estradiolin the endothelial cells bya variety of aromatases.[51]
      5. Vitamin K2, 2-4 mg.[52], [53], [54], [55], [56], [57], [58], [59]
  3. Other measurable factors
    1. A number of medications are arterial dialators,the most well known of which is nitroglycerine tablets or paste. They stimulate the production of nitrous oxide by the endothelial cell layer which directly dialates middle to small arteries. Nitrates should not be used around the clock, because the endothelial cells become tolerant and nonresponsive to the nitrous oxide message; this can be reversed with Vitamin C.[60]
      1. L-Arginine[61] is a direct substrate for nitrous oxide production by the endothelial cells, and is sometimes called the poor man's Viagra. Thorne Research makes a sustained release form called Perfusia-SR.
      2. Iloprost is a drug used to treat pulmonary hypertension by relaxing the arteries of the lung. It is thought to act like Prostacyclin (PGI-2).[62]
      3. Niacin flush is the rapid dialation of peripheral blood vessels induced byexcess niacin, or nicotinic acid. Sustained release forms make this effect for tolerable. Niaspan 500 mg→ 2000 mg before bed.
      4. Sauna bath/cold shower alternating induces rapid dialation and contraction of peripheral arterioles.
      5. Meditation may well enhance arterial elasticity, by normalizing autonomicnerve balance as measured by Heart Rate Variability on ANSAR testing.

If decreased arterial elasticity of small blood vessels as measured by CVProfile*is as early and reversible as we hope, some combination of these factors, individualized to a given patient should show improvement in months to a years time. As with the oft repeated prayer, "Let there be five aces in the deck.", no combination of these substances is likely to reverse this common pathway of aging in the absense of significant lifetstyle changes that include regular aerobic exercise and mediterranean diet with fish at least twice a week, olive oil,and lots of fruits and veggies.

CVProfiler, Hypertension Diagnostics Inc., (888) 785-7392

I. Full Basic program, Day # 1:12-18 capsules

1) Multivitamin- Daily One without Iron by Twin Labs, Life Extension One a Day, Centrum Silver or equivalent for a) B complex b) Selenium 200 mcg c) Chromium 200 mcg

2) Country Life Superior C 1000 mg, or Life Ext. #0927 with quercetin or equivalent

3) Life Extension Vitamin D3, 1000 i.u.,2-4 capsules/day

4) Magnesium Oxide 400 mg, or Magnesium Citrate 250-500 mg

5) Life Extension Super Booster, with

a) Mixed Vitamin E, 400 mg

b) Vitamin K1 & K2 ( MK-4 and MK-7), 2-4 mg

c) Lutein,2mg

d) Lycopene, 10 mg

6) Life Extension Max EPA/DHA, or Solgar 700 omega-3 capsules, 1-4 a day

7) Life Extension Mitochondrial Energy Optimizer (#1268). Fourcaps contain a)Carnosine 1000 mg, Benfotiamine 150 mg,Pyridoxamine 50 mg, b)Acetyl-L-Carnitine arginate 750 mg, R-Lipoic acid 150 mg

8) ThorneResearchPerfusia SR, 1-2 capsules twice a day

a) L-Arginine 1000 mg sustained release

9) Nicotinic acid to tolerance or Niaspan 500 mg → 2000 mg/day.

II. Follow up at one months' time

1. Repeat CVP arterial elasticity test.

2. Consider Homocysteine*, hs-CRP*, Chem screen panel* Lipoprotein (a) Coenzyme Q10 Hormonal levels, PSA, E- 2/E-16 ratio, DHEAS. *Will probably not be covered by Medicare. Individualize patient's program byaddressing the most significant discovered risk factor first. Enhance musculoskeletal function and revisit lifestyle issues.

III. Basic Abbreviated Programs, 4, 6, 8 and 12

1. Lifestyle changes

a) Exercise to aerobic capacity ≥ 3x a week

b) Caloric restriction to Ideal Body Weight

c) Meditation, neurobiofeedback

d) Pomegranates, blueberries, apples, etc.

e) Chocolate with lecithin

f) Salmon, sardines, krill, cold water fish

2. Basic 4, 6, 8, and 12

a)LEF Super Booster

b)LEF One a Day or Twin Labs Daily One (Centrum,etc)

c)LEF Vitamin C or Country Life Superior C, 1000 mg

d)LEF Vitamin D3, 1000 i.u., or Solgar Vitamin D3

e)LEF Max EPA/DHA omega-3, or Solgar 700 omega-3

f)LEF Mitochondrial Energy Optimizer

g)Magnesium Oxide 400 mg or equivalentNiacin?

h)Thorne Research Perfusia SR, twice/day Pantothenate? Ribose ? FOCUSEDLEF endothelial defense?

i. Serum Coenzyme Q10 ? CoQ10 100-400 mg BID

ii. DHEAS ?DHEA 10-50 mg Q am

iii. Fr. & Tot. testosterone?Testosterone 1-2% gel topical Q am PSA Free and Total?

iv. E 16/2 ratio? Biest/Progesterone topical

v. Homocycteine? 5MTHF, Vit. B6 50 mg, Vit. B-12 sublingual or im, Trimethylglycine

vi. ANA ? anticardiolipin? John H. Juhl, D.O. October 16, 2009

[1] Scanu Angelo M, Lipoprotein (a) a genetic risk factor for premature coronary heart disease, JAMA, June 24 1992;267(24): 3326-29.

[2] Carlson LA, et.al., Pronounced lowering of serum levels of lipoprotein (a) in hyperlipidemic subjects treated with nicotinic acid, Journal of Internal Medicine, 1989;226(4): 271-76.

[3] Toth Peter P, Lipoprotein (a): a new treatment target? Consultant, Jul;y 2007: 755-6.

[4] Ergul Adviye, Jupin Dena, et. Al., elevated endothelin-1 levels are associated with decreased arterial elasticity inhypertensive patients, The Journal of Clinical Hypertension, Aug 2006; V 8 # 8: 549-.

[5] Yoe HY, Kim OY, et.al., Independent inverse relationship between serum lycopene concentration and arterial stiffness, Atherosclerosis, published online ahead of print, August 13, 2009.

[6] Timmerman MF, Van der VeldenU, et.al. Java project on periodontal diseases: the relationship between vitamin C and the severity opf periodontitis, J Clin Peridontol, 2007;34(4): p 299-304.

[7] Dietrich M, Block G, et.al., Vitamin C supplementation decreases oxidative stress biomarker f2-isoprostanes in plasma of nonsmokers exposed to environmental tobacco smoke, Nutr Cancer, 2003;45: p 176-84.

[8] Corey Cahill L, El-Sohemy A, Vitamin C deficiency in a population of young Canadian youths, AmJ Epidemiol, 2009; 170(4): p 464-71.

[9] Liuba Petru, Odemarsky Michael, Lykkesfeld Jens, Higher vitamin C levels associated with improved vascular function in type I diabetes, published online 6/24/2009 in The American Journal of Clinical Nutrition.

[10] Kuri S, Tuomainen TP, Laukkanen JA, et.al., Plasma vitamin C modifies the association between hypertension and risk of stroke, Stroke,2002;33(June): p 1568-73

[11] Simons LA, Von Konigsmark M, Balasubramaniam S,“What dose of vitamin e is required to reduce susceptibility of LDL to oxidation?, Aust N Z J Med, 1996;26: p 496-503.

[12] Davey PJ, et.al., Cost-effectiveness of vitamin e therapy in the treatment of patients with angiographically proven coronary narrowing (CHAOS trial), Cambridge heart antioxidant study, Am J Cardiol, 1998;82: p 414-17.

[13] Hodis HN, et.al., Serial coronary angiographic evidence that antioxidant vitamin intake reduces progressionof coronary artery atherosclerosis, JAMA, 1995; 273: 1849-.

[14] Lauretani F, Ferrucci L, et.al., Low plasma selenium concentrationsand mortality among older community-dwelling adults: the In CHIANTI Study, Aging Clin Exp Res, 2008; 20(2): 2\153-8.

[15] Akbaraly NT, Hininger-Favier I, et.al., Plasma selenium over time and cognitive decline in the elderly, Epidemiology, 2007; 18(1): 52-8.

[16] Mertz W, Schwarz K, relation of glucose tolerance factor to inmpaired glucose tolerance in rats on stock diets, Am J Physiol, 1959; 196: 614-18.

[17] Albarracin CA, Fuqua BC et.al., Chromium piccolinate and biotin combination improves glucose metabolism in treated uncontrolled overweight to obese patients with type 2 diabetes, Diabetes Metab Res Rev, 2008; 24(1): 41-51.

[18] Bartlett HE, Eperjesi F, Nutritional Supplementation for type 2 diabetes: a systematic review, Ophthalmic Physiol Opt, 2008;28(6) p 503-23.

[19] Brownson C, Hipkiss AR, Carnosine reacts with a glycated protein, Free Radical Biology and Medicine, 2000; 28(10): 1564-70.

[20] Hipkiss AR, et.al., Reaction of carnosine with aged proteins: another protective process?, Annals of the New York Academy of Sciences, 2002; 959: 285- 94.

[21] Wang AM, et.al., Use of carnosine as a natural anti-senescence3 drug for human beings, Biochemistry (Moscow), 2000; 65(7): 869-71

[22] Elliot Paul, Chambers JC, et.al., Genetic loci associated with C-Reactive Protein levels and risk of coronary heart disease, JAMA, July 1, 2009;V 302#1: p 37.

[23] Schleithoff S, et.al., “High dose vitamin D shows anti-inflammatory effects in CHF", Am J Clin Nutrit., 2005;83: p 754-59, reviewed by Erik Goldman in Holistic Primary Care, summer 2006.

.[24] Forman JP, Giovannucci E, et.al., Plasma 25-hydroxyvitamin D levels and risk of incident hypertension, Hypertension, march 19, 2007, Epub ahead of print.

[25] MartinsD, WolfM, et.al., Prevalence of cardiovascular risk factors and serum levels of 25-hydroxyvitamin D in the United States: data from the third national health and nutrition examination survey, Arch Intern Med, 2007; 167(11): 1159-65.

[26] Pfeifer M, begerow B, et.al., effects of a short term vitamin D3 and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women, J Clin Endocrinol Metab, 2001;86(4): 1633-7.

[27] Li YC, Vitamin D regulation of the rennin-angiotensin system, J Cell Biochem, 2003 feb1; 88(2):327-31.

[28] Pittas AG, Lau J, The role of vitamin D and calcium in type 2 diabetes, A systemic review and metaanalysis, J Clin Endocrinol Metab, 2007; 92(6): 2017 -29.

[29] Life Extension 9/11/09 review, Folic acid supplementation improves blood flow in peripheral arterial disease, British Journal of Surgery, September 2009, double blind trial comparing folic acid,MTHF, and placebo.

[30] Guo H, Chi J, et.al., Influence of folic acid on plasma homocysteine levels and arterial endothelial function in patients with unstable angina, Indian J Med Res, 2009; 129(3): 279-84.

[31] Pooya s, Jalali MD, et.al., The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialoehyde levels of type 2 diabetic patients, Nutr Metab cardiovasc Dis, 6/18 2009; Epub ahead of print.

[32] Matsuzaki M yokoyamja M, et.al., Incremental effects of eicosapentanoic acid on cardiovascular events in statin-treated patients with coronary artery disease, Circ J, 2009; 73(7): 1283-90.

[33] Control of arterial tone after long-term coenzyme Q10 supplementation in senescent rats, British Journal of Pharmacology (UK), 1998;124(7): 1500-06.

[34] Langsjoen H, Langsjoen P, Willis R, Folkers K, Usefulness of coenzyme Q10 in clinical cardiology: a long term study, Mol Aspects Med (ENGLAND), 1994, 15 Suppl: p 165-75

[35] Aiqun MA, Wanggong Zhang, Zhiquan Liu, Effect of Protection and repair of injury of mitochondrial membrane-phospholipid on prognosis in patients with dilated cardiomyopathy, Blood Pressure, 1996; 5 (suppl 3): 53-55.

[36] Soja AM, Mortensen SA, Treatment of chronic cardiac insufficiency with coenzyme Q10, results of Meta-analysis in controlled clinical trials, Ugeskr Laeger, 1997 December 1;159(49): 7302-7308.

[37] BrevettiG, Chiariello M, Ferulano G, et.al., Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind cross-over study, Circulation,1988;77: p 767-73.

[38] Smith JC, et.al., “Androgen Deprivation Therapy is associated with greater arterial stiffness and less arterial compliance", J Clin Endocrinol Metab, 2001;86: p 4261-67.

[39] Faloon William, Protection against arterial calcification, bone loss, cancer and againg, Life Extension, 2009 Jan: 15(1): p 63-75.

[40] Alexandersen P, Haarbo J christinasen C, The relationship of natural androgens to coronary heart disease in males: a review, Atherosclerosis, 1996; 125: 1-13.

[41] Lesser M, testosterone propionate therapy in one hundred cases of angina pectoris, J Clin Endocrinol, 1946;6: 549-57.

[42] Phillips GB, et.al., the association of hypotestosteronemia with coronary artery disease in men, Arterioscler Thromb, 1994;14" 701-6.

[43] Kazmarek A, et.al., the association of lower testosterone level with coronary artery disease in postmenopausal women, Int J Cardiol, 2003 Jan;87(1): 53-7.

[44] Webb CM, McNeill JG, et.al., Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease, Circulation, 1999;100: 1690- 96.

[45] Shores MM, Matsumoto AM, et.al., Low serum testosterone and mortality in male veterans, Arch Intern Med, 2006;166:1660-65.

[46] Hayashi T, et.al., DHEA retards atherosclerosis formation through its conversion to estrogens: the possible role of nitrix oxide, Arterioscler Throm Vasc Biol, 2000;20: 782-92.

[47] Kawano H, Yasue H, et.al., Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men, J Clin Endocrinol Metab, 2003;88:3190-95.

[48] Villareal DT, Holloszy JO, Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial, JAMA, 2004 Nov 10; 292(18): 2243-8.

[49] Feldman HA, et.al., Loe DHEA and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study, Am J Epidemiol, 2001;153: 79-89.

[50] Wright Jonathan, Maximize Your Vitality and Potency for Men over 40, 1999, Smart Publications.

[51] Nathan, et.al., Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase, Proc Natl Acad Sci USA, 2001;98)6): p 3589-93.

[52] Faloon William, Protection against arterial calcification, bone loss, cancer and aging, Life Extension, 2009 Jan; 15(1): p 63-75.

[53] Schurgers LJ, Dissel PE, Spronk HM, et.al., Role of Vitamin K and vitamin K-dependent proteins in vascular calcification, Z Kardiol, 2001; 90 Suppl 3: 57-63.

[54] Geleijnse JM, Vermeer C, et.al., Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study, J Nutr, 2004 Nov;134(11): 3100-05.

[55] Beulens JW, et.al., High dietary menaquinone intake is associated with redeuced coronary calcification, Atherosclerosis, 2008 Jul 19: epub ahead of print.

[56] Schurgers LJ, Spronk HM, et.al., Regression of warfarin induced medial elastocalcinosis by high intake of vitamin K in rats, Blood, 2007 April 1;109 (7): 2823-31.

[57] Doherty TM, Asotra K, et.al., Calification in atherosclerosis: bone biology and chronic inflammationat the arterial crossroads, Proc Natl Acad Sci USA, 2003 Sept 30; 100(20): 11201-6.

[58] Shea Mk, O'Donnell CJ, et.al., Vitamin K supplementation and progression of coronary artery calcium in older men and women, Am J Clin Nutr, 2009 April 22; Epub ahead of print.

[59] Gast GCM, de Roos NM, et.al., A high menaquinone diet reduces the incidence of coronary disease in women, Nutr Metab Cardiovasc Dis, 2009; Epub ahead of print.

[60] Watanabe H, Kakihana M, Ohtsuka S, Sugishita Y, Randomized, double-blind, placebo controlled studyon the preventive effect of ascorbate on nitrate tolerance in patients with congestive heart failure, Circulation,1998;97: p 886-91.

[61] Lucotti P, Monti L, et.al., Oral L-arginine supplementation improves endotherlial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass, Metabolism, july 8 2009; Epub ahead of print.

[62] Keith Robert, Drug significantly improves smoking-caused lung damage in former smokers: presentation on Aug 2 2009 at the International Association for the study of Lung Cancer meeting in San Francisco, reportedin Life Extension daily news print version, 8/5/2009.