A Report from the First International Mini-Symposium on Methionine Restriction and Lifespan

Methionine is an essential amino acid. Our metabolism cannot produce it, but is nonetheless an important raw material for the manufacture of proteins, and thus must be obtained in the diet. If you don't obtain enough of it, you die. Fortunately just about any sensible diet, and even most deficient diets, contain far more than you actually need to get by. Very few foodstuffs are lacking in methionine.

If you are the sort who likes undertaking strict and novel diets for the inherent challenge involved, rather than the outcome, then you should give up whatever you are doing right now and give a low methionine diet a try. You will be faced with challenging research to identify appropriate levels of methionine for a human low methionine diet, poor and contradictory nutritional data on the methionine content of various foodstuffs, and a comprehensive avoidance list that includes most of the standard staples and fallback alternatives used in the recipes of any given culinary tradition. I feel quite sorry for those who are forced into such a diet through suffering one of a few rare medical conditions such as homocystinuria, as the challenges inherent in organizing your own low methionine diet almost rise to the level of making the expensive tailored medical diets produced by a variety of big name companies look cost-effective.

Why undertake a low methionine diet if not forced to do so by pressing medical circumstances? For the same reasons one would undertake calorie restriction or intermittent fasting, both of which are far easier propositions: just like these two options, methionine restriction has been shown to extend life and improve health in a range of laboratory species. The evidence for calorie restriction to bring health benefits to human practitioners is compelling, and further bolstered by a mountain of animal studies results accumulated over decades. In the case of methionine restriction there is, so far as I know, only very sparse data for humans, but a good enough set of data from rodent studies to make it interesting. Methionine restriction is likely an important underlying mechanism for the operation of calorie restriction, which makes sense as a lesser intake of food generally means a lesser intake of methionine. Thus anyone advocating that you give methionine restriction a try for health reasons would argue on the basis of studies in mammals that strongly suggest it is a cause of calorie restriction benefits, and then point to the supporting data mountain for calorie restriction.

Caveat emptor, of course. I'm one who has in the past debated whether it is wise to try alternate day fasting given that there is much more data for straight calorie restriction, so you can probably imagine my views on methionine restriction. Being a conservative late adopter in all things has a lot going for it.

In a like fashion the research community is generally very conservative and and slow-moving in most matters. It takes a while, sometimes decades, for research to percolate through the system. Methionine restriction is beginning to be considered more widely among those who work with calorie restriction or fasting, however. So we have the small symposium noted below, for example, as a sign that folk are talking on this topic. Where there is presently discussion and modest scientific meetings there will later be conferences and commercial ventures - and possibly better and more reliable information on whether and how to practice methionine restriction were one inclined to do so:

The First International Mini-Symposium on Methionine Restriction and Lifespan

It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met) ingestion by rats extends lifespan. Since then, several studies have replicated the effects of dietary methionine restricted (MR) in delaying age-related diseases.

We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY, September 2013. The goals were (1) to gather researchers with an interest in MR and lifespan, (2) to exchange knowledge, (3) to generate ideas for future investigations, and (4) to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH), and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones, and the adipose tissue were discussed.

The symposium also emphasized the value of other species, e.g., the naked mole rat, Brandt's bat, and Drosophila, in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies.

Among the presentations discussed is one of the only studies on methionine restriction in humans I've seen, preliminary and brief as it was. It is worth noting in passing that in comparison to the mild reduction in methionine here, rodent life span studies on methionine restriction tend to cut down methionine levels in the diet by a much larger proportion.

Previous findings in rodent models that dietary MR increases maximum lifespan and reduces the development of aging-related impairments suggest that MR may have important implications as a preventive or therapeutic strategy in humans. However, to date, there have been few studies aimed at translating these pre-clinical findings to the clinic.

To this end, we conducted a short-term controlled cross-over feeding study of MR in healthy adults. This study consisted of two isocaloric diet groups (control and 86% MR). Our objectives were to determine the feasibility of feeding an MR diet and to assess the effects of MR on relevant blood biomarkers. The study was conducted with 12 healthy adults and consisted of two 3-week experimental feeding periods with a 2-week washout. The MR diet was well-tolerated by all subjects with no negative side-effects reported.

Decreases in plasma levels of Met (22%) and cysteine (15%) were observed in the MR group after 3 weeks. MR significantly decreased plasma total cholesterol (15%), LDL (23%), and uric acid (25%), but had no effects on leptin, adiponectin, IGF-1, or glutathione.

Altogether, these findings demonstrate the feasibility of a MR diet in humans and indicate that MR has significant short-term effects on blood lipids similar to those observed in laboratory animal models. In addition, the lack of effects on blood adipokines and glutathione are consistent with more recent laboratory findings that indicate that restrictions in both Met and Cys may be required for the full range of beneficial effects on adipokines and longevity.