benefits of folates independent of homocysteine lowering have also been reported. Potential mechanisms include antioxidant actions, effects on cofactor availability, or direct interactions with the enzyme endothelial NO synthase
beneficial effects of folates on cardiovascular risk
Combination of DHA, EPA, choline, phospholipids, Folate, B12, B6, vitamin C and E, and selenium improves memory and cognitive function in those with mild Alzheimer's disease.
Percent survival at 1 year was significantly increased in patients treated with immunotherapy than in those treated with supportive care alone (9/25 vs. 3/25, p < 0.05) in study which suggests that low-dose subcutaneous IL-2 plus melatonin may be effective as a second-line therapy to induce tumor regression and to prolong percent survival at 1 year in metastatic colorectal cancer patients progressing under 5-FU and folates
Folic acid inversely associated with brain atrophy. Also, homocysteine is associated directly with brain atrophy in the cortical, subcortical, and hippocampus regions.
Although currently no drugs that specifically target mitochondrial biogenesis in HF are available, acceleration of this process through adenosine monophosphate–activated kinase (AMPK), endothelial nitric oxide synthase (eNOS), and other pathways may represent a promising therapeutic approach
Mitochondrial biogenesis can be enhanced therapeutically with the use of adenosine monophosphate kinase (AMPK) agonists, stimulants of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway (including phosphodiesteraes type 5 inhibitors), or resveratrol
metformin, a commonly used antidiabetic drug that activates AMPK signaling
Recent evidence suggests that the eNOS/NO/cGMP pathway is an important activator of mitochondrial biogenesis
BH4 (tetrahydrobiopterin) supplementation can prevent eNOS uncoupling and was found to reduce left ventricular hypertrophy
folic acid is known to replenish reduced BH4 and has been shown to protect the heart through increased eNOS activity
Both folate deficiency and inhibition of BH4 synthesis were associated with reduced mitochondrial number and function
Resveratrol, a polyphenol compound responsible for the cardioprotective properties of red wine, was recently identified as a potent stimulator of mitochondrial biogenesis
epidemiological studies reveal a reduced risk of cardiovascular disease in premenopausal, but not post-menopausal, women compared with men
I would hypothesis that a change in the predominance of ER expression is one of ER beta to ER alpha: creating a more pro-inflammatory signal.
The majority of ROS in the heart appear to come from uncoupling of mitochondrial electron transport chain at the level of complexes I and III
Because the majority of ROS in HF comes from mitochondria, these organelles are the primary target of oxidative damage.
cardioprotective therapies such as angiotensin-converting enzyme inhibitors and ATII receptor blockers were shown to possess antioxidant properties, although it is not known whether they target mitochondrial ROS directly or indirectly
The most common MTHFR mutation is called the MTHFR C677T mutation
Another common mutation is called MTHFR A1298C
Having only one mutation, ie, being heterozygous, is, from a medical perspective, irrelevant. Even when 2 MTHFR mutations are present (eg, 2 C677T mutations, or one C677T mutation and one A1298C mutation)
Although these mutations do impair the regulation of homocysteine, adequate folate levels essentially
“cancel out” this defect.
Regardless of whether you have an MTHFR mutation in both genes or not, the treatment for elevated homocysteine is the same—dietary intervention and supplementation
with folic acid and vitamins B6 and B12
Overall, evidence from these studies indicates that, so long as the homocysteine level is normal, MTHFR mutations do not significantly increase the risk of heart attack or stroke
Studies investigating the association of MTHFR mutations and venous blood clots have been inconsistent, with some studies showing a slight association, but most studies
have not shown any association
lowering homocysteine reduced the rate of coronary restenosis. A combination of folic acid, Vitamin B12, and Vitamin B6 were used to lower homocysteine.
A common tool to monitor the progression of atherosclerosis is carotid intima-medial thickness. This meta-analysis showed that folic acid reduces carotid intimal medial thickness.
Vitamin B12, B6, and folic acid shown to lower homocysteine levels and decreased the incidence of stroke. However, overall mortality and CVD deaths were not.