We've discussed how limiting dietary methionine in the nutrition forum can lead to impressive gains in longevity.
It turns out that niacin can deplete methionine (PMID 11895163), in this study involving very high doses of niacin:
There is some evidence pointing to methionine intake, not homocysteine level, as being a more fundamental health measure. In The atherogenic effect of excess methionine intake (PMID 14657334, full text here). They found that even when homocysteine was not elevated, a methionine rich diet in mice caused heart disease.Since niacin is excreted predominantly as methylated pyridones, requiring methionine as a methyl donor, the present study was undertaken to examine whether metabolism of the amino acid is altered in the presence of large doses of niacin. Male Sprague-Dawley rats were given a nutritionally adequate, semi-synthetic diet containing niacin at a level of either 400 or 1000mg/kg diet (compared to 30mg/kg in the control diet) for up to 3 months. Supplementation with niacin (1,000 mg/kg diet) for 3 months resulted in a significant increase in plasma and urinary total homocysteine levels; this increase was further accentuated in the presence of a high methionine diet. The hyperhomocysteineaemia was accompanied by a significant decrease in plasma concentrations of vitamins B6 and B12, which are cofactors for the metabolism of homocysteine. The homocysteine-raising action of niacin, in particular, has an important toxicological implication, as hyperhomocysteineaemia is considered to be an independent risk factor for arterial occlusive disease. The niacin-associated change in homocysteine status may be an important limiting factor in the use of this vitamin as a lipid-lowering agent.
Since methionine can be depleted by niacin, might niacin be a stand in for dietary methionine reduction and lead to increased longevity? The title of PMID 3782631, Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin, at least shows that niacin provides a longevity benefit.Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model. Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.
StephenBThe Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.
