**7. Conclusion**

Pathophysiology and Clinical Aspects of 28 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

neural tube defects, preeclampsia, spontaneous abortion, and premature delivery (Dasarathy et al., 2010). This is pertinent as it is believed that placental thrombosis may

In the case of deficiency of one or more vitamins involved in homocysteine metabolism, blood levels of this amino acid are often elevated well above those observed in the healthy population. Treatment of hyperhomocysteinemia includes supplementation with mostly pharmacological doses of one or more of the relevant B vitamins and is generally effective in reducing homocysteine concentrations and delays atherosclerotic and thrombotic

The negative impact of particular genotypes on homocysteine levels can partly be compensated by folate intake and is, even in smaller part, dependent on several other variables that affect homocysteine levels (see Table 2). For example, if persons have balanced diet with optimal intake of B6 and B12 vitamins and folates it seems that the C677T mutation and the subsequent reduced activity of the enzyme MTHFR do not connect with hyperhomocysteinemia (Schriver et al., 1995; Silaste et al., 2001). Besides, folic acid supplemetation reduces the plasma homocysteine concentration in all three genotypes (TT,

This scientific evidence suggests that the MTHFR C677T genetic mutation influences folate metabolism, leading to the conclusion that dietary intake of a standard dosage of folate may be insufficient for half to two-thirds of the population with this mutation (Meshkin & Blum,

In the case of CBS deficiency, the enzyme activity can effectively be enhanced by treatment

A combination of all three relevant coenzymes to treat milder forms of hyperhomocysteinemia resulted in a clear 50% reduction of plasma homocysteine levels. However, given alone, only folic acid was able to induce similar reductions, whereas vitamin B 12 was little effective and vitamin B6 failed to show an effect (Perry et al., 1968,

Many countries have implemented mandatory folic acid fortification of flour and grain products to reduce the risk of various diseases. Besides, individuals can find a good source

For individuals with unexplained arterial or venous blood clots and unexplained atherosclerosis it seems appropiate having blood homocysteine levels checked. One can also argue that everybody with atherosclerosis, patients with CVD, heart attacks, or strokes, should have their blood checked for homocysteine levels. All this in order to prevent further

**6. Who should be tested for MTHFR mutations and homocysteine levels** 

contribute to the pathogenesis of these conditions (Gatt & Makris, 2007).

The treatment of hyperhomocysteinemia varies with the underlying cause.

CT and CC) of the MTHFR C677T mutation (Meshkin & Blum, 2007).

of folate in fruits and vegetables (especially green leafy vegetables).

**5. Treatment of hyperhomocysteinemia** 

events.

2007).

with large doses of vitamin B6.

Ubbink et al., 1993; Ubbink et al., 1994).

Elevated homocysteine concentration has been identified as an independent risk factor for premature cardiovascular disease.

Results of multiple prospective and case control studies have shown that patients with a moderately elevated plasma homocysteine concentration are more likely to develop venous and arterial thrombosis compared to the control population. Homocysteine seems to promote atherothrombosis by a variety of mechanisms. The precise pathogenic mechanism remains to be confirmed and it is not yet clear whether homocysteine itself or a related metabolite or a cofactor is primarily responsible for the atherothrombogenic effects of hyperhomocysteinemia. However, recent studies indicate that lowering an elevated homocysteine level does decrease the risk of atherosclerosis and blood clots. Until this issue has been more clearly defined, it appears prudent to make an effort to try to lower one's homocysteine levels through supplementation with B vitamins, which is an efficient and safe way to reduce an elevated homocysteine levels.

The MTHFR mutations appear to be medically irrelevant, as long as an individual's homocysteine level is normal. Therefore, it should be first the homocysteine level, not the MTHFR genetic status, to be tested in patients with or at risk for blood clots, atherosclerosis, or pregnancy complications.

It is well estabilished that healthly lifestyle lowers homocysteine concentrations. So the most important in everyday life is awareness that the level of homocysteine in blood is strongly influenced by several lifestyle factors such as nutrition, stress, smoking cigarettes, alcohol consumption, or physical inactivity. And therefore, exercise is a commonly recommended lifestyle intervention for individuals at risk for, or diagnosed with, cardio vascular disease. More specifically, we suggest that exercise, mild in aged people, but especially heavy physical activity, exerts its most favorable effect in subjects with hyperhomocysteinemia.
