Plasma homocysteine

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

Briddon, A., Total plasma homocysteine as part of the routine aminogram by ion-exchange chromatography, Amino Acids, 15, 235, 1998. 

Heavy coffee drinking raises the levels of plasma homocysteine, a risk for heart disease. The dose response of plasma homocysteine to coffee appears stronger than the association to serum cholesterol levels. Heavy coffee consumption was found to cause an increase of about 2 mmol/... 

Silaste M, Rantala M, Alftham G, Aro A and Kessaniemi Y. 2003. Plasma homocysteine concentration is decreased by dietary intervention. Br J Nutr 89 295-301. 

Homocystinuria can be treated in some cases by the administration of pyridoxine (vitamin Bs), which is a cofactor for the cystathionine synthase reaction. Some patients respond to the administration of pharmacological doses of pyridoxine (25-100 mg daily) with a reduction of plasma homocysteine and methionine. Pyridoxine responsiveness appears to be hereditary, with sibs tending to show a concordant pattern and a milder clinical syndrome. Pyridoxine sensitivity can be documented by enzyme assay in skin fibroblasts. The precise biochemical mechanism of the pyridoxine effect is not well understood but it may not reflect a mutation resulting in diminished affinity of the enzyme for cofactor, because even high concentrations of pyridoxal phosphate do not restore mutant enzyme activity to a control level. 

Mijatovic V, Netelenbos C, van der Mooren MJ, de Valk-de Roo GW, Jakobs C, Kene-mans P (1998) Randomized, double-blind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women. Fertil Steril 70 1085-1089... 

Jacques PF, Bostom AG, Williams RR, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996 93 79. 

Haagsma, C. J., Blom, H. J., van Riel, P. L., et al. (1999) Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 58, 79-84. 

CA027 Urgert, R., T. van Vliet, P. L. Zock, and M. B. Katan. Heavy coffee consumption, and plasma homocysteine a randomised controlled trial in healthy volunteers. Am J Clin Nutr 2000 72(5) 1107-1110. 

Recent evidence supports the premise that lowering elevated plasma homocysteine levels may reduce the risk of coronary heart disease... 

Olthof, M.R., Bioavailability of Flavonoids and Cinnamic Acids and their Effect on Plasma Homocysteine in Humans, PhD Thesis, Wageningen University, 2001. 

Rasmussen K, Mailer J, Lyngbak M (1999) Within person variation of plasma homocysteine and effects of posture and tourniquet application. Clin Chem 45 1850-1855... 

C. J. Boushey et al., A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease Probable Benefits of Increasing Folic Acid Intakes, J. Am. Med. Assoc. 274 (1995) 1049-57. 

Vitamins B6, B12, and folate An elevated plasma homocysteine level is associated with increased cardiovascular risk (see p. 263). Homocysteine, which is thought to be toxic to the vascular endothelium, is converted into harmless amino acids by the action of enzymes that require the B vitamins—folate, B6 (pyridoxine), and B12 (cobalamin). Ingesting foods rich in these vitamins can lower homocysteine levels and possibly decrease the risk of car diovascular disease. Folate and B6 are found in leafy green veg etables, whole grains, some fruits, and fortified breakfast cereals. B12 comes from animal food, for example, meat, fish, and eggs. 

In patients taking maximal doses of sulfonylureas, plasma homocysteine concentrations were raised during secondary failure with poor metabolic control, which may indicate increased vascular risk (71). The concentrations correlated inversely with endogenous insulin concentrations. 

Drzewoski J, Czupryniak L, Chwatko G, Bald E. Total plasma homocysteine and insulin levels in type 2 diabetic patients with secondary failure to oral agents. Diabetes Care 1999 22(12) 2097-9. 

Stulc T, Melenovsky V, Grauova B, Kozich V, Ceska R. Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy. Nutrition 2001 17(9) 721-3. 

Westphal S, Dierkes J, Luley C. Effects of fenofibrate and gemfibrozil on plasma homocysteine. Lancet 2001 358(9275) 39-40. 

Some antiepileptic drugs have been associated with low serum and erythrocyte folate concentrations and high total plasma homocysteine concentrations in some patients. The concentrations of folate and homocysteine have been measured in 42 patients taking carbamazepine and 42 matched healthy controls (241). Patients taking carbamazepine had significantly lower serum and erythrocyte folate concentrations. There was hyperhomocystinemia (over 15 gmol/l) in 24% of the patients and 5% of the controls. 

Lamberti P, Zoccolella S, Iliceto G, Armenise E, Fraddosio A, de Mari M, Livrea P. Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson s disease patients. Mov Disord 2005 20 69-72. 

Paran, E. and Engelhard, Y. 2001. Effect of Lyc-O-Mato, standardized tomato extract on blood pressure, serum lipoproteins, plasma homocysteine and oxidative stress markers in grade 1 hypertensive patients. In Proceedings of the 16th Annual Scientific Meeting of the Society of Hypertension , San Francisco, USA. 

Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer s disease. N Engl J Med 2002 346(7) 476-483. 

Todesco L, Angst C, Litynski P, Loehrer F, Fowler B, Haefeli WE. Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age. Eur J Clin Invest 1999 29 1003-1009. 

Rea IM, McMaster D, Woodside JV, Young IS, Archbold GP, Linton T, Lennox S, McNulty H, Harmon DL, Whitehead AS. Community-living nonagenarians in Northern Ireland have lower plasma homocysteine but similar methylenetetrahydrofolate reductase thermolabile genotype prevalence compared to 70-89-year-old subjects. Atherosclerosis 2000 149 207-214. 

Moderately elevated plasma homocysteine, defined as levels between 15 and 30 jimol/L (5), has emerged as a new risk factor for ischemic heart disease and stroke (6). 

In the Heart Outcomes Prevention Evaluation 2 (HOPE-2) study, 5522 patients aged 55 or older with vascular disease or diabetes were randomized to treatment with either placebo or a combination 2, 5 mg of folic acid, 50 mg vitamin B6, and I mg vitamin B 2, for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke. Mean plasma homocysteine levels decreased by 2.4 jimol/L in the treatment group and increased by 0.8 jimol/L in the placebo group. The primary outcome occurred in 18.8% of patients assigned to active therapy and in 19.8% of those assigned to placebo (relative risk = 0.95 95% Cl = 0.84-1.07 P = 0.41) (68). 

The difference between the outcome of the Swiss Heart Study and that of FACIT illustrates how difficult it is to explain the results in terms of the biological effects of vitamin therapy. The positive results of the Swiss Heart Study seem to confirm the classical homocysteine hypothesis, which holds that homocysteine is an important atherosclerotic determinant and that lowering of homocysteine with vitamin therapy might reduce the rates of cardiovascular events. However, it is more difficult to explain the results of FACIT by an adverse effect of low plasma homocysteine, and consequently, a less simplistic perspective on the methionine-homocysteine metabolism and the multiple effects of folate, B6, and B 2 is needed. 

Hultberg B, Andersson A, Sterner G. Plasma homocysteine in renal failure. Clin Nephrol 1993 40(4) 230-235. 

Arnadottir M et al. The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients. Clin Nephrol 1993 40(4) 236-240. 

Vanizor Kural B, et al. Plasma homocysteine and its relationships with atherothrombotic markers in psoriatic patients. Clin Chim Acta 2003 332( I -2) 23-30. 

Arnadottir M, Hultberg B. Treatment with high-dose folic acid effectively lowers plasma homocysteine concentration in cyclosporine-treated renal transplant recipients. Transplantation 1997 64(7) 1087. 

Brilakis ES, et al. Lack of association between plasma homocysteine and angiographic coronary artery disease in the era of fortification of cereal grain flour with folic acid. Atherosclerosis 2002 165(2) 375 381. 

Jonasson T, et al. Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease-a prospective randomized study of vitamin supplementation, Clin Chem Lab Med 2005 43(6) 628-634. 

Jonasson X Ohlin H, Andersson A, Arnadottir A, Hultberg B. Renal function excerts only a minor influence on high plasma homocysteine concentration in patients with acute coronary syndromes, Clin Chem Lab Med 2002 40(2) 137-142. 

Zarychanski R, Houston DS. Plasma homocysteine concentration is not associated with activated protein C resistance in patients investigated for hypercoagulability. Thromb Haemost 2004 91 (6) I I 15-1 122. 

Sauls DL, Wolberg AS, Hoffman M. Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability implications for the mechanism of thrombosis in hyperhomocysteinemia. J Thromb Haemost 2003 l(2) 300-306. 

Schnyder G, et al. Association of plasma homocysteine with restenosis after percutaneous coronary angioplasty. Eur Heart J 2002 23(9)726-33. 

Wong CK, et al. Lack of association between baseline plasma homocysteine concentrations and restenosis rates after a first elective percutaneous coronary intervention without stenting. Heart 2004 90(l I) 1299-1302. 

Schnyder G, et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001 345(22) 1593-1600. 

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