Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial

Heijer, Martin den; Willems, Huub P. J.; Blom, Henk J.; Gerrits, W. B. J.; Cattaneo, Marco; Eichinger, Sabine; Rosendaal, Frits R.; Bos, Gerard M.J.

doi:10.1182/blood-2006-04-014654

Cited by 240 publications

(138 citation statements)

References 23 publications

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“…Confirmation of the causal nature of this association requires randomized controlled trials of homocysteine lowering. The only completed trial among venous thrombosis patients did not show any benefit in prevention of recurrent events using 5 mg folic acid, 50 mg pyridoxine, and 0.4 mg cyanocobalamin, compared with placebo, administered daily in 701 patients with previous idiopathic venous thrombosis (45). About one-half of participants in this study had hyperhomocysteinemia, so results can be considered fairly conclusive in refuting the homocysteine hypothesis.…”

Section: Homocysteinementioning

confidence: 49%

“…We estimate that in 1990 there were 18,500 cases of venous thromboembolism among obese people aged 45-64 years (based on the number of people in that age range, a prevalence of obesity of 10% at that time, and the expected rate of thrombosis in obesity compared to a normal weight). However, in 2000, we estimate that with a 25% prevalence of obesity, there were 62,000 cases of thrombosis among obese persons aged [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. If the prevalence of obesity had remained 10% in 2000, only 24,000 cases of thrombosis would have been expected in obese persons in this age group in that year.…”

Section: Modifiable Risk Factors Obesitymentioning

confidence: 99%

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Epidemiology and Risk Factors for Venous Thrombosis

Cushman

2007

Seminars in Hematology

628

449

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Venous thrombosis, including deep vein thrombosis and pulmonary embolism, occurs at an annual incidence of about 1 per 1000 adults. Rates increase sharply after around age 45 years, and are slightly higher in men than women in older age. Major risk factors for thrombosis, other than age, include exogenous factors such as surgery, hospitalization, immobility, trauma, pregnancy and the puerperium and hormone use, and endogenous factors such as cancer, obesity, and inherited and acquired disorders of hypercoagulation. This review focuses on epidemiology of venous thrombosis and the general implications of this in patient management.

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Section: Homocysteinementioning

confidence: 49%

Section: Modifiable Risk Factors Obesitymentioning

confidence: 99%

Epidemiology and Risk Factors for Venous Thrombosis

Cushman

2007

Seminars in Hematology

628

449

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“…The effect of Hcy lowering by supplementation of B vitamins on the risk reduction of venous thromboembolism has been investigated by den Heijer in a randomized, placebocontrolled, double-blind trial (28) . Overall, the rate of recurrent venous thrombosis did not signifi cantly differ between patients treated with vitamins and those with placebo (i.e., 12.2 % vs. 14.3 % ).…”

Section: Where Do We Go From Here ?mentioning

confidence: 99%

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Lippi

Plebani

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Homocysteine is a sulfur-containing amino acid, which is synthesized from the precursor methionine through a multi-step process, and then reconverted to methionine or catabolyzed into cysteine. The presence of vitamin B9 (folic acid), vitamin B6 (pyridoxine) and vitamin B12 (cobalamin) is essential in homocysteine metabolism, wherein defi ciency of one or more of these nutrients is associated with various degree of hyperhomocysteinemia. There is little doubt that hyperhomocysteinemia is associated with several human disorders, such as cardiovascular disease, neurodegenerative disorders, pregnancy complications and fractures, so that its measurement might be useful for risk assessment. Nevertheless, several randomized homocysteine-lowering therapy trials have failed to show that supplementation with vitamins B substantially modifi es (and -more importantly -improves) the end points and the related outcomes. According to the current state of scientifi c knowledge, it seems thus reasonable to conclude that lowering homocysteine alone is probably insuffi cient to mitigate the risk of thromboembolic, cardiovascular and neurodegenerative disorders inasmuch as this bizarre amino acid acts in strict synergy with other probably more powerful risk factors. Several lines of evidence suggest, however, that its measurement may be helpful for identifying subjects at greater risk of disease, who may thus benefi t from a more aggressive treatment of other modifi able risk factors, as recently shown by result of the 5-year Fenofi brate Intervention and Event Lowering in Diabetes (FIELD) trial.

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“…This is not only supported by human 234 population studies identifying it as an independent risk factor, but strong evidence resides in 235 animal models with diet-and/ or genetic-based elevations in homocysteine concentrations [36, 236 37]. However, clinical trials targeting homocysteine management by the utilization of B-vitamin 237 supplementation as a means to lower circulating homocysteine concentrations have not been as 238 effective as anticipated [38][39][40][41]. Numerous reviews have debated the various explanations for 239 these findings and the associative vs. causal role of homocysteine in vascular disease [42][43][44].…”

mentioning

confidence: 99%

Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model

Neuman¹,

Albright²,

Schalinske³

2013

Nutrition Research

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Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is associated with numerous pathological conditions. A number of nutritional and hormonal factors have been shown to influence circulating homocysteine concentrations; however, the impact of exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-independent manner. The purpose of this study was to determine the influence of exercise on homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate hyperhomocysteinemia. Female outbred mice (12 weeks old) were assigned to either a sedentary or free-access wheel exercise group. Following a 4-week acclimation period, half of the mice in each group were provided a folate-restricted diet for 7-weeks prior to euthanasia and tissue collection. As expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total homocysteine concentrations; however, exercise completely prevented the increase in circulating homocysteine concentrations. Moreover, exercise reduced plasma homocysteine concentrations 36% within the group fed only the control diet. The prevention of hyperhomocysteinemia by exercise appears, at least in part, to be the result of increased folate-independent homocysteine remethylation owing to a 2-fold increase in renal betaine homocysteine S-methyltransferase. To our knowledge, this is the first report demonstrating the prevention of hyperhomocysteinemia by exercise in a dietary folate-restriction model. Future research will be directed at determining if exercise can have a positive impact on other nutritional, hormonal, and genetic models of hyperhomocysteinemia relevant to humans. Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is 30 associated with numerous pathological conditions. A number of nutritional and hormonal factors 31 have been shown to influence circulating homocysteine concentrations; however, the impact of 32 exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was 33 that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-34 independent manner. The purpose of this study was to determine the influence of exercise on 35 homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate 36 hyperhomocysteinemia. Female outbred mice (12 wk old) were assigned to either a sedentary or 37 free-access wheel exercise group. Following a 4-wk acclimation period, half of the mice in each 38 group were provided a folate-restricted diet for 7-wk prior to euthanasia and tissue collection. As 39 expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total 40 homocysteine concentrations; however, exercise completely prevented the increase in circulating 41 homocysteine concentrations. Moreover, exercise reduced plasma homocysteine c...

show abstract

Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial

Cited by 240 publications

References 23 publications

Epidemiology and Risk Factors for Venous Thrombosis

Epidemiology and Risk Factors for Venous Thrombosis

Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model

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