So I am aware that rat studies do not translate well into human models, for academic purposes I wanted to ask how one might convert that 40% reduction into a mg/kg amount for humans. Would one base such calculation on the RDA or the average intake of adults 19 and older?
I've seen another study that reported decreased IGF-1 via protein restriction which was in the order of 760 mg/kg (total protein) per day, the decrease was more pronounced than that for severe CR. They stated that this amount was very close to the median protein requirement in a healthy adult. Mitochondrial reactive oxygen species were not reported unfortunately. See free full text:
Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans
"In conclusion, our findings demonstrate that, unlike in rodents, long-term severe CR does not reduce total and free IGF-1 levels in healthy humans if protein intake is high. In addition, our data suggest that chronic protein intake is more powerful than calorie intake in modulating circulating IGF-1 concentration in humans. This is important because the median protein requirement of the healthy adult population is 0.65 g kg−1 per day and the reference daily intake (97.5th percentile) is 0.83 g kg−1 of body weight per day (Rand et al., 2003) that is close to the protein intake of our vegan group in this study. In contrast, half of the US males are eating 40% or more protein (≥ 1.34 g kg−1 per day) than the reference daily intake (Moshfegh et al., 2005), which is presently considered to be harmless and, according to public opinion and advocators of ‘low-carb’ diets, may even be beneficial. More studies are necessary to understand the biological and clinical implications of a chronic high protein intake, especially in sedentary people with a positive family history for cancer. In addition, more studies are needed to understand the effects of PR and methionine restriction on metabolism, disease prevention and longevity in humans, because several studies in rodents have shown major beneficial effects (Richie et al., 1994; Miller et al., 2005;Pamplona & Barja, 2006; Sanz et al., 2006). Finally, these findings underscore the importance of dietary macronutrient intake in regulating metabolic events, and suggest that reduced protein intake may become an important component of anti-aging and anticancer dietary interventions, due to the importance of IGF-1 in the biology of aging (Sonntag et al., 1999; Flurkey et al., 2001; Holzenberger et al., 2003;Ikeno et al., 2003; Kenyon, 2005; Kurosu et al., 2005; Bonkowski et al., 2006; Russell & Kahn, 2007) and in the pathogenesis of many human tumors (Samani et al., 2007; Sachdev & Yee, 2007)."
It seems clear that methionine control can be achieved using a diet very low in animal proteins, which on a methionine/cal basis far exceed plant sources of protein. Of the plant sources lentils have notably little methionine when compared with soy beans which are still considered to be 'poor' sources of methionine.(1) Plant sources of protein are also not as easily absorbed as animal protein (80% vs. 90% respectively) (2). As seems logical, vegan diets are considered to be poor sources of methionine as well (3). Vegans are also noted as having lower IGF-1 levels than omnivores or ovo-lacto-vegetarians. (4)
(1) http://0-www.sciencedirect.com.wam.city.ac.uk/science/article/pii/S0306987708003836?np=y
(2) Ibid
(3) Ibid
(4) Ibid
From the full text article on vegan diets:
The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy
Mark F. McCart, Jorge Barroso-Aranda, Francisco Contreras http://dx.doi.org/10...ehy.2008.07.044
http://www.ncbi.nlm....pubmed/18789600
"Vegans can keep their Met intakes relatively low by moderating their intakes of soy products and legumes, while diluting their total protein intake by ingesting ample amounts of fruit, wine, and/or beer. (Note however the comparatively low-Met density of lentils – on a mg per kcal basis, marginally higher than that of wheat or brown rice – and lower than that of oatmeal!) Protein dilution could also be achieved by including more plant oils in the diet; whether this would be advisable may hinge on the long-term impact of increased oil intake on insulin sensitivity. Very-low-fat diets coupled with exercise training can have a rapid insulin-sensitizing impact and in the longer term promote leanness [52], [53] and [54] – effects that down-regulate insulin secretion, which should be favorable from a longevity standpoint [1]. However, it is conceivable that some lean, well-exercised individuals could increase their dietary intake of unsaturated oils without notably impairing their insulin sensitivity or leanness – studies have not yet assessed the impact of dietary fat modulation within the context of a vegan diet and regular exercise.
Theoretically, effective Met availability might be further reduced by ingesting supplemental glycine, which is inexpensive, delicious, and has anti-inflammatory effects which are potentially protective [55]. However, since dietary Met has an inductive impact on expression of glycine N-methyltransferase [56] and [57], dietary glycine may be less effective as a functional Met antagonist in the context of a low-Met diet.
Whether a feasible strategy of Met restriction, implemented consistently over most of a lifetime, could have a sufficient impact on Met availability to achieve a meaningful delay in the human aging process, remains a matter of speculation. To date, we still await confirmation that caloric restriction can increase maximal lifespan in primates to a worthwhile extent. Perhaps one way to assess the likely impact of a Met-restricted diet on human longevity would be to examine the long-term impact of such a diet on oxidation of mitochondrial DNA in leukocytes – though whether Met restriction influences this particular parameter in rodents is not yet known, as the relevant studies have targeted mitochondria obtained from liver or heart.
In any case, regular consumption of a low-fat, whole-food vegan diet, coupled with exercise training, is likely to have a favorable impact on mean longevity by reducing risk for cancers, coronary disease, and diabetes[45], [58], [59] and [60]. However, low systemic IGF-I activity seems likely to increase risk for hemorrhagic stroke, and possibly ischemic stroke as well, and is associated with poor prognosis following an ischemic stroke [61], [62], [63], [64] and [65]. Furthermore, in Asian cultures, increasing intakes of animal products and total protein have been associated with declining stroke risk [66], [67], [68], [69] and [70]. Since stroke is an uncommon cause of death in most strains of rodents, calorie/protein restriction studies in rodents can cast little light on the impact of such measures on stroke risk in humans. Vegans would thus be well advised to keep their blood pressures in the low-normal range throughout life, by employing a potassium-rich, low-salt diet, exercising, and staying lean [61].
Met plays a role in the endogenous synthesis of various “carninutrients”, including l-carnitine, creatine, and taurine, that are not supplied by vegan diets, and that may play important roles in health promotion [71]. Thus, supplementation with these agents may be warranted in vegans practicing a Met-restricted diet. Furthermore, since selenium occurs naturally in foods primarily as protein-bound selenomethionine – substituted for Met in proteins – it follows that a low-Met diet is prone to be a low-selenium diet; selenium supplementation may be prudent for vegans who are trying to keep their Met intakes low [72]. Unsupplemented vegan diets are devoid of vitamin D, so vegans who lack access to year-round uv light should be sure to include this in their supplementation regimens [73]. And it should go without saying that supplementation with vitamin B12 is mandatory for vegans [74]."
Edited by LexLux, 11 April 2014 - 01:06 AM.
