This article presents a further exploration of the risk factors underlying cardiometabolic (CM) disease and their identification and management within an integrative medicine framework as illustrated by the case of a 30-year-old obese African American male who presented for a follow-up visit with regard to his metabolic syndrome (MeS).
This article reviews in detail the pathophysiology of common nutrient depletions and their contribution to CM disease risk, as well as drug-induced nutrient depletions incurred during treatment for CM disease and the MeS. The review also includes a detailed discussion on the evaluation and treatment of nutrient deficiencies.
The article concludes with a detailed discussion of the case resolution. Following an extensive metabolic evaluation, a program of specific nutrient repletion was instituted alongside testosterone replacement therapy in addition to instituting stress reduction techniques and herbal supplements to improve his physiologic stress response. The patient returned to clinic after 3 months to review progress and laboratory results. He had lost 15 pounds, reported increased energy levels, and complete elimination of joint aches. He was scheduled to return to the clinic after a further 3 months for re-evaluation.
Get full access to this article
View all access options for this article.
References
1.
GrundyS.M., CleemanJ.I., DanielsS.R., DonatoK.A., EckelR.H., et al.Diagnosis and management of the metabolic myndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 2005; 112:2735–2752.
2.
CAHCIM. Definition of Integrative Medicine. Developed and Adopted by The Consortium of Academic Health Centers for Integrative Medicine (CAHCIM), May2004. Edited May 2009.
3.
NahinR., BarnesP.M., StussmanB.J., BloomB.Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners: United States, 2007. Natl Health Stat Report, 2009; 18:1–14.
4.
NealR.Report by David M. Eisenberg, M.D., on complementary and alternative medicine in the United States: overview and patterns of use. J Altern Complement Med, 2001; 7(Suppl 1):S19–21.
5.
FordE.S., LiC., McGuireL.C., MokdadA.H., LiuS.Intake of dietary magnesium and the prevalence of the metabolic syndrome among U.S. adults. Obesity (Silver Spring), 2007; 15(5):1139–1146.
6.
VolpeS.L.Magnesium, the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus. Crit Rev Food Sci Nutr, 2008; 48(3):293–300.
7.
HolickM.F.Vitamin D deficiency. N Engl J Med, 2007; 357:266–281.
8.
ReisJP, von MühlenD, MillerER3rd, MichosED, AppelLJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics, 2009; Aug 3:.[Epub ahead of print].
9.
EpelE.S.Psychological and metabolic stress: a recipe for accelerated cellular aging?. Hormones, 2009; 8(1):7–22.
10.
ParsonsP.A.The ecological stress theory of aging and hormesis: an energetic evolutionary model. Biogerontology, 2007; 8:233–242.
11.
ChrousosG., GoldP.The concepts of stress and stress system disorders. JAMA, 1992; 267:1244–1252.
12.
YuB.P., ChungH.Y.Adaptive mechanisms to oxidative stress during aging. Mech Aging Dev, 2006; 127(5):436–443.
13.
TakaseB., AkimaT., UehataA., OhsuzuF., KuritaA.Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans. Clin Cardiol, 2004; 27(4):223–227.
14.
LimaM.de L., CruzT., RodriguesL.E., BomfinO., MeloJ., CorreiaR., et al.Serum and intracellular magnesium deficiency in patients with metabolic syndrome – evidences for its relation to insulin resistance. Diabetes Res Clin Pract, 2009; 83(2):257–262.
15.
PaolissoG., ScheenA., D’OnofrioF., LefèbvreP.Magnesium and glucose homeostasis. Diabetologia, 1990; 33:511–514.
16.
AlaimoK, McDowellMA, BriefelRR, BischofAM, CaughmanCR, LoriaCM, et al.Dietary intake of vitamins, minerals and fiber of persons age 2 months and over in the United States: Third National Health and Nutrition Examination Survey, phase 1, 1988-91. Adv Data Vital Health Stats, 1994; 258:1–28.
LimaM.L., CruzT., PousadaJ.C., BarbosaK., CangucV.The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care, 1998; 21:682–686.
19.
KaoW.H., FolsomaR., NietoF.J., BrancatiF.L.Serum and dietary magnesium and the risk of type 2 diabetes mellitus and atherosclerosis risk in community study. Arch Intern Med, 1999; 159:2151–2159.
20.
HeK., SongY., BelinR.J., ChenY.Magnesium intake and the metabolic syndrome: epidemiologic evidence to date. J Cardiometab Syndr, 2006; 1(5):351–355.
21.
BoS., DurazzoM., GuidiS., CarelloM., SacerdoteC., SilliB., et al.Dietary magnesium and fiber intakes and inflammatory and metabolic indicators in middle-aged subjects from a population-based cohort. Am J Clin Nutr, 2006; 84(5):1062–1069.
22.
SeeligM.Cardiovascular consequences of magnesium deficiency and loss: pathogenesis, prevalence and manifestations – magnesium and chloride loss in refractory potassium repletion. Am J Cardiol, 1989; 63(14):4G–21G.
23.
AlturaB.M., AlturaB.T.New perspective on the role of Mg in the pathophysiology of the cardiovascular system. I. Clinical aspects. Magnesium, 1985; 4:226–244.
24.
DubeyA., SolomonR.Magnesium, myocardial ischaemia and arrhythmias: the role of magnesium in myocardial infarction. Drugs, 1989; 37:1–7.
25.
DelvaP.Magnesium and coronary heart disease. Mol Aspects Med, 2003; 24(1–3):63–78.
26.
SongY., LiT.Y., van DamR.M., MansonJ.E., HuF.B.Magnesium intake and plasma concentrations of markers of systemic inflammation and endothelial dysfunction in women. Am J Clin Nutr, 2007; 85(4):1068–1074.
27.
DjurhuusM.S., SkøttP., Hother-NielsonO., KlitgaardN.A., Beck-NielsenH.Insulin increases renal magnesium excretion: a possible cause of magnesium depletion in hyperinsulinemic states. Diabet Med, 1995; 12(8):664–669.
28.
HwangD.L., YanC.F., NadlesJ.L.Insulin increases intracellular magnesium transport in human platelets. J Clin Endocrinol Metab, 1993; 76:549–553.
29.
PenumathsaS.V., ThirunavukkarasuM., SamuelM., ZhanL., MaulikG., BagchiM., et al.Role of niacin-bound chromium (NBC) in ameliorating the symptoms of metabolic syndrome. J Am Coll Nutr, 2007; 25(483):H820–H826.
30.
VincentJ.The biochemistry of chromium. J Nutr, 2000; 130:715–718.
31.
BalkE.M., TatsioniA., LichtensteinA.H., LauJ., PittasA.G.Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care, 2007; 30(8):2154–2163.
32.
Zafra-StoneS., YasminT., BagchiM., ChatterjeeA., VinsonJ.A., BagchiD.Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res, 2007; 51:675–683.
33.
PreussH.G., AndersonR.A.Chromium update: examining recent literature 1997–1998. Curr Opin Clin Nutr Metab Care, 1998; 1:509–512.
34.
Zafra-StoneS., BagchiM., PreussH.G., BagchiD.Benefits of chromium(III) complexes in animal and human health. In: VincentJ.B. editor. The Nutritional Biochemistry of Chromium(III). Amsterdam: Elsevier; 2007. p. 183–206.
35.
RavinaA., SlezakL., MirskyN., BrydenN.A., AndersonR.A.Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med, 1999; 16(2):164–167.
36.
DixonK.M., DeoS.S., WongG., SlaterM., NormanA.W., BishopJ.E., et al.Skin cancer prevention: a possible role of 1,25dihydroxyvitamin D3 and its analogs. J Steroid Biochem Mol Biol, 2005; 97(1–2):137–143.
37.
NagpalS., NaS., RathnachalamR.Noncalcemic actions of vitamin D receptor ligands. Endocr Rev, 2005; 26:662–687.
38.
DanescuL.G., LevyS., LevyJ.Vitamin D and diabetes mellitus. Endocrine, 2009; 35:11–17.
39.
LielY., UlmerE., SharyJ., HollisB.W., BellN.H.Low circulating vitamin D in obesity. Calcif Tissue Int, 1988; 43:199–201.
40.
PalomerX., González-ClementeJ.M., Blanco-VacaF., MauricioD.Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab, 2008; 10:185–197.
41.
SmithS.M., GardnerK.K., LockeJ., ZwartS.R.Vitamin D supplementation during Antarctic winter. Am J Clin Nutr, 2009; 89(4):1092–1098.
42.
NemerovskiC.W., DorschM.P., SimpsonR.U., BoneH.G., AaronsonK.D., BleskeB.E.Vitamin D and cardiovascular disease. Pharmacotherapy, 2009; 29(6):691–708.
43.
XiangW., KongJ., ChenS., CaoL.P., QiaoG., ZhengW., et al.Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab, 2005; 288:E125–E132.
44.
MüllerK., HaahrP.M., DiamantM., RieneckK., KharazmiA., BendtzenK.1, 25- Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level. Cytokine, 1992; 4:506–512.
45.
ScraggR., SowersM.F., BellC.Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the third national health and nutrition examination survey. Am J Hypertens, 2007; 20:713–719.
46.
SugdenJ.A., DaviesJ.I., WithamM.D., MorrisA.D., StruthersA.D.Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med, 2008; 25:320–325.
47.
MelamedM.L., MuntnerP., MichosE.D., UribarriJ., WeberC., SharmaJ., et al.Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004. Arterioscler Thromb Vasc Biol, 2008; 28:1179–1185.
48.
TargherG., BertoliniL., PadovaniR., ZenariL., ScalaL., CigoliniM., et al.Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness in type 2 diabetic patients. Clin Endocrinol, 2006; 65:593–597.
49.
LindénV.Vitamin D and myocardial infarction. Br Med J, 1974; 3:647–650.
50.
PilzS., MärzW., WellnitzB., SeelhorstU., Fahrleitner-PammerA., DimaiH.P., et al.Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study referred for coronary angiography. J Clin Endocrinol Metab, 2008; 93:3927–3935.
51.
DobnigH., PilzS., ScharnaglH., RennerW., SeelhorstU., WellnitzB., et al.Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med, 2008; 168:1340–1349.
52.
WangT.J., PencinaM.J., BoothS.L., JacquesP.F., IngelssonE., LanierK., et al.Circulation. Vitamin D deficiency and risk of cardiovascular disease. Circulation, 2008; 117(4):503–511.
53.
ParkerJ., HashmiO., DuttonD., MavrodarisA., StrangesS., KandalaN.B., et al.Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas, 2010; 65(3):225–236.
54.
WebbA.R., KlineL., HolickM.F.Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab, 1988; 67:373–378.
55.
KumarJ, MuntnerP, KaskelFJ, HailpernSM, MelamedML. Prevalence and associations of 25-hydroxyvitamin D deficiency in US Children: NHANES 2001-2004. Pediatrics, 2009; Aug 3.[Epub ahead of print].
56.
GreenbergS., FishmanW.H.Coenzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol, 1990; 30:596–608.
57.
MechanickJ.I., BrettE.M., ChausmerA.B., DickeyR.A., WallachS.American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals. Endocr Pract, 2003; 9:417–470.
58.
LampertiC., NaniA.B., LucchiniV., PrelleA., BresolinN., MoggioM., et al.Muscle coenzyme Q10 level in statin related myopathy. Arch Neurol, 2005; 62(11):1709–1712.
59.
KishiH., KishiT., FolkersK.Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10 enzymes by clinically used anti-hypertensive drugs. Res Commun Chem Pathol Pharmacol, 1975; 12:533–540.
60.
KishiT., WatanabeT., FolkersK.Bioenergetics in clinical medicine. XV. Inhibition of coenzyme Q10 enzymes by clinically used adrenergic blockers of B-receptors. Res Commun Chem Pathol Pharmacol, 1977; 17:157–164.
61.
SinghR.B., NiazM.A., RastogiS.S., ShuklaP.K., ThakurA.S.Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens, 1999; 13:203–208.
62.
RotigA., AppelkvistE.L., GeromelV., ChretienD., KadhomN., EderyP., et al.Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet, 2000; 356(9227):391–395.
LazarouJ., PemeranzB.H., CoreyP.N.Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA, 1998; 279(15):1200–1205.
65.
KleefstraN., HouwelingS.T., BakkerS.J., VerhoevenS., GansR.O., Meyboom de JonB., et al.Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care, 2007; 30:2154–2163.
66.
LauF., BagchiM., SenC., BagchiD.Nutrigenomic basis of beneficial effects of chromium (III) on obesity and diabetes. Mol Cell BioChem, 2008; 317:1–10.
StearnsD.M., WiseJ.P.Sr., PatiernoS.R., WetterhahnK.E.Chromium (III) picolinate produces chromosomal damage in chinese hamster ovary cells. FASEB J, 1995; 9(15):1643–1648.
69.
ViethR.Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr, 1999; 69(5):825–826.
70.
HollisB.W.Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr, 2005; 135(2):317–322.
71.
ZitaC., OvervadK., MortensenS.A., SindbergC.D., MoesgaardS., HunterD.A.Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study. Biofactors, 2003; 18(1–4):185–193.
72.
CasoG., KellyP., McNurlanM.A., LawsonW.E.Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am J Cardiol, 2007; 99:1409–1412.
73.
ThibaultA., SamidD., TompkinsA.C., FiggW.D., CooperM.R., HohlR.J., et al.Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res, 1996; 2:483–491.
74.
KimW.S., KimM.M., ChoiH.J., YoonS.S., LeeM.H., ParkK., et al.Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Invest New Drugs, 2001; 19:81–83.
75.
RosenfeldtF.L., HaasS.J., KrumH., HadjA., NgK., LeongJ.-Y., et al.Conezyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens, 2007; 21:297–306.
76.
LangsjoenP., LangsjoenP., WillisR., FolkersK.Treatment of essential hypertension with CoQ10. Mol Aspects Med, 1994;(15 Suppl):S265–S272.
77.
LinnaneA.W., KopsidasG., ZhangC., YarovayaN., KovalenkoS., PapakostopoulosP., et al.Cellular redox activity of coenzyme Q10 effect of CoQ10 supplementation on human skeletal muscle’. Free Radic Res, 2002; 36(4):445–453.
78.
KellyG.S.Rhodiola rosea: a possible plant adaptogen. Altern Med Rev, 2001; 6(3):293–302.
79.
YokogoshiH., KobayashiM., MochizukiM., TerashimaT.Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res, 1998; 23:667–673.
80.
KobayashiK., NagatoY., AoiN., JunejaL.R., KimM., YamamotoT., et al.Effects of L-theanine on the release of alpha-brain waves in human volunteers. Nippon Nogei Kagakukaishi, 1998; 72:153–157.
81.
EschenauerG., SweetB.V.Pharmacology and therapeutic uses of theanine. Am J Health Sys Pharm, 2006; 63(1):26–30.
