Jump to content

Recommended Posts

This very recent article captured my attention, since it deals with CR in a context of nutritional geometry (macros ratios) and tackles the issue of protein 'restriction'.

 

Dietary protein, aging and nutritional geometry

Stephen J. Simpsona,b,∗, David G. Le Couteur a,c, David Raubenheimer a,b, Samantha M. Solon-Biet a, Gregory J. Cooneya, Victoria C. Cogger a,c, Luigi Fontana d,e,f

Please cite this article in press as: Simpson, S.J., et al., Dietary protein, aging and nutritional geometry. Ageing Res. Rev. (2017), http://dx.doi.org/10.1016/j.arr.2017.03.001

 

 

Nearly a century of research has shown that nutritional interventions can delay aging and age- related diseases in many animal models and possibly humans. The most robust and widely studied intervention is caloric restriction, while protein restriction and restriction of various amino acids (methionine, tryptophan) have also been shown to delay aging. However, there is still debate over whether the major impact on aging is secondary to caloric intake, protein intake or specific amino acids. Nutritional geometry provides new perspectives on the relationship between nutrition and aging by focusing on calories, macronutrients and their interactions across a landscape of diets, and taking into account compensatory feeding in ad libitum-fed experiments. Nutritional geometry is a state-space modelling approach that explores how animals respond to and balance changes in nutrient availability. Such studies in insects and mice have shown that low protein, high carbohydrate diets are associated with longest lifespan in ad libitum fed animals suggesting that the interaction between macronutrients may be as important as their total intake.

Edited by mccoy

Share this post


Link to post
Share on other sites

This is a very interesting set of figures, where the red lines indicate the longest lifespan routes (hi carb, low protein), whereas the blue lines are the shortest lifespan routes (hi proteins, low carb). Y axis is carbs, x axis is proteins, decreasing values approaching the origin. The coloured surface (iso-caloric surface) I think is the experimental area, where real data have been collected.

post-7347-0-94223300-1491942154_thumb.jpg

 

 

It is notable that the ratio of protein to carbohydrates (1:10) that optimizes lifespan is similar across species. It is also of note that most of these studies found that the protein content of these diet was less than 10%, or about one third of standard laboratory diets. The results of these Geometric Framework experiments are consistent with the meta-analyses by Nakagawa et al. and Speakman et al. (Nakagawa et al., 2012; Speakman et al., 2016). They found that the lowest risk of mortality occurred when protein content was between 10 and 30% of total calories (Fig. 1B, D) with increasing mortality as protein content increases. Nakagawa et al. (2012) also show that very low protein is associated with reduced

viability. Interestingly, the longest living population in the world, the Japanese citizens of the island of Okinawa, have traditionally eaten a diet where the protein intake is 9%, and the macronutrient ratio of protein to carbohydrates is 9:85, almost identical to the ratio found to optimize lifespan in the Geometric Framework animal studies (Le Couteur et al., 2016b). There are a number of observational studies in humans that have reported the influence ofthe ratio of protein to carbohydrates. These were reviewed by Pedersen et al. (Pedersen et al., 2013). The studies did not report the benefit of low protein, high carbohydrate diets per se, but conversely reported that harmwas associated with high protein, low carbohydrate diets. It was concluded that low carbohydrate, high protein diets are possibly associated with an increase in all-cause mortality, type 2 diabetes mellitus and

cardiovascular disease. Animal- based protein and other animal product-based diets had the worst effects, while vegetable- based proteins and other vegetable product-based diets reversed the trends. This is consistent with the subsequent NHANES study published by Levine et al. showing that the problems associated with a higher protein diet in people under 65 years of age are abrogated by the consumption of vegetable- rather than animal-based protein (Levine et al., 2014). These studies suggest that the source of protein may be as important as the amount of protein in the diet. Overall, there seems to be consistency across interventional studies in animals and observational studies in humans that the ratio of protein to carbohydrate influences lifespan in ad libitum fed settings. Therefore, the interactions between macronutrients as well as the actual amounts per se influence age-related health. It is of interest that we have found that the ratio of glucose and branched chain amino acids (as surrogate markers of carbohydrate and protein intake) influences key aging pathways such as mTOR, FGF21 and insulin (Solon-Biet et al., 2014, 2016) suggesting that the interactions between macronutrients at the dietary level may reflect cellular responses of the nutrient sensing pathways. In this review we have focused on energy and total macronutrients and their effect on health and aging. However it is important to recognize that the composition of the macronutrients influence health.Withrespectto proteinand carbohydrates, plant-based protein has health benefits compared to animal-based proteins (Levine et al., 2014; Pedersen et al., 2013) while complex carbohydrates are likely to be beneficial compared to simple sugars (Suter, 2005).

 

Share this post


Link to post
Share on other sites

As an aside, I'm wondering about the following statement:

 

With respect to protein and carbohydrates, plant-based protein has health benefits compared to animal-based proteins (Levine et al., 2014; Pedersen et al., 2013) while complex carbohydrates are likely to be beneficial compared to simple sugars (Suter, 2005).

 

What's the cause of the cited health benefits? I don't think it's just lower Meth and Leu, since in increasing amounts and good variability essential AAs in a plant-based diet can be as high or higher than in an animal-based regimen. Or maybe the above statement is valid in terms of equal total protein.

 

The advantage of complex carbs is obviously related to the lower insulin signal.

Share this post


Link to post
Share on other sites

Last section of the article deals with aminoacid restriction

 

 

6. Amino acid restriction While the Geometric Framework methodology aims to study the relationship between protein and aging in a very broad dietary context, there has also been considerable interest in narrowing in on restricting specific amino acids that might mediate the effect of dietary protein on aging. Animals consume less of a food lacking a single essential amino acid compared with otherwise identical food and preferentially choose food containing all essential amino acids (Chaveroux et al., 2010). While animals provided with low protein food tend to increase food consumption through protein leverage, food lacking an essential amino acid is associated with food aversion. Therefore, a low protein diet will be associated with increased food consumption (Solon-Biet et al., 2014) while a diet lacking an essential amino acid will be associated with reduced food consumption and an increase in foraging and altered food choices (Gietzen and Aja, 2012). Restricting individual amino acids influences food and calorie intake, which may have secondary effects on lifespan and aging. Methionine is a sulphur-containing essential amino acid. Methionine restriction, of about 65- 80% of standard intake, has been shown to increase lifespan in yeast, C. elegans, Drosophila and rodents (McIsaac et al., 2016; Pamplona and Barja, 2006; SanchezRoman and Barja, 2013). One of the first studies of methionine restriction was performed in rats where the methionine content of chow was reduced from 0.86 to 0.17%. This reduced food intake per rat (between 10 and 25% over the lifespan) and body weight while lifespan was increased by 30% (Orentreich et al., 1993). Subsequent studies confirmed that methionine restriction increased maximum lifespan by 10–20% in rodent models (McIsaac et al., 2016; Miller et al., 2005) and Drosophila (Grandison et al., 2009). Methionine restriction has been shown to increase circulating levels of FGF21 (Lees et al., 2014), reduce glucose, IGF1, T4 and insulin (Miller et al., 2005) and mitochondrial oxidative stress (Sanchez-Roman and Barja, 2013). This overlaps with those pathways influenced by caloric restriction and it has been suggested that reduced methionine intake contributes to the effects of protein restriction and caloric restriction on lifespan, particularly via its beneficial effects on mitochondrial oxidative stress (Sanchez-Roman and Barja, 2013) and increased hydrogen sulphide production (Hine et al., 2014). Interestingly, plant-based proteins are lower in methionine than animal proteins which may explain their health and aging benefits (McIsaac et al., 2016; SanchezRoman and Barja, 2013) that have been documented in humans (Levine et al., 2014; Pedersen et al., 2013). Tryptophan is an aromatic essential amino acid thatis also a precursor to neurotransmitters such as serotonin. There have been a few older studies in rodents showing that tryptophan restriction to 30–40% of control values increases lifespan (De Marte and Enesco, 1986; Ooka et al., 1988; Segall and Timiras, 1976). Low levels of tryptophan in the dietlead to reduced food intake, growth and body weight(Ooka et al., 1988). There have been few if any recent studies of tryptophan restriction. The branched chain amino acids leucine, isoleucine and valine and are of particular interest to aging biology because they activate mTORandincrease insulinsecretion. For example,low protein,high carbohydrate diets in mice were found to be associated with low circulating levels of branched chain amino acids, which correlated with phosphorylation of hepatic mTOR (Solon-Biet et al., 2014) and increased levels of FGF21 (Solon-Biet et al., 2016). Fontana et al.(Fontana et al., 2016) recently showed that reducing branched chain amino acids by two thirds in mice led to improved glucose tolerance, while reduction of the other six essential amino acids (including tryptophan and methionine) had no effect. The low amino acid diet was associated with increased FGF21 levels but surprisingly,the low branched chain amino acids had no effect. Elevated branched chain amino acids are a marker of diabetes mellitus in humans (Giesbertz and Daniel, 2016), yet supplementation with branched chain amino acids has been reported to increase lifespan in mice (D’Antona et al., 2010) and nematode worms (Mansfeld et al., 2015). Application of nutritional geometry may provide new interpretations of these amino acid conclusions. In all these studies, the interventions are compared to a standard diet or standard concentrations of amino acids without considering what a normal diet might be in evolutionary of physiological terms. For example, many proteins and amino acids are toxic in high doses,therefore an improvement in outcome with restriction may reflect a reduction in exposure to toxic levels. Therefore, a range of dietary concentrations is necessary, not so much to determine whether amino acid restriction is beneficial, but in order to determine the optimum amino acid concentration for lifespan. Nutritional geometry also focusses on interactions between nutrients. This is important when the concentration of a single nutrientis restricted as an intervention, because it must be replaced by another/other nutrients, and this might lead to substantial changes in the ratios between nutrients. For example, we found that mTOR phosphorylation was influenced both by glucose and branched chain amino acids, indicating that the ratio of nutrients can impact on basic cellular processes (Solon-Biet et al., 2014).

 

Share this post


Link to post
Share on other sites

Nice find. I have been following the nutritional geometry developments. Nice overview of some of them by Joshua Mitteldorf here: http://joshmitteldorf.scienceblog.com/2016/09/05/nutritional-geometry/

 

I refer to the following paper below: http://www.sciencedirect.com/science/article/pii/S1550413114000655

 

As the explanatory narrative is told, it is a low protein to carbohydrate ratio as opposed to percent protein, low being ideal, that is key.

 

I am not convinced at this point the above narrative is 100% accurate. Even if we can translate from rodents to humans, the quality of the food ( e.g.- what kind of food matrix, what fatty acids in what ratio, etc ) may impact influence on longevity both directly and also secondary to mediating changes in rodent appetite.

 

Both low protein groups did better than the high protein groups, with low protein high carb doing better than low protein high fat. Would the results have been the same if the fat was mostly monounsaturated from the best rodent EVOO?

 

Interestingly, the low protein high fat group that did not do as well ate more and gained more weight than the low protein high carb group, leading to a more diabetogenic phenotype . This is all ad libitum as I understand it.

 

Humans can change their diet based on more than satiation though. If the the rodents made the choice to have fewer calories in the low protein, high fat group to keep the same phenotype as the low protein high carbohydrate group, might they have fared just as well?

 

Notably either way both of these low protein groups, not surprisingly did better than the high protein groups ( mTOR, IGF-1, etc). This is despite the higher protein groups gaining less weight since high quality protein is more satiating than the other macronutrients ( he did not study lower quality protein less enriched in essential amino acids, but he does in your reference other work that poor quality protein sources with fewer BCAA, etc does the opposite and leads to relative food avoidance and foraging behavior ... I hope to see more work coming out of this in the future).

 

So too much protein relative to other macronutrients at least in this animal model is deleterious, independent of ( and despite! ) calorie intake , but this does not exclude the possibility that some or all the difference observed between the high carb and high fat interventions of the low protein diets are due to differences in how much the rodents chose to eat, with implications on the genreralizability to people who can make optimal food choices.

 

Consistency around other sources of evidence is key. Though the authors in your paper describe a consistency of findings using similar methodology across multiple species, and also cited the Okinawans, with their renowned longevity, as having a near ideal ratio of C:P of nearly 10:1

 

This is provocative, but the macronutrient percentages in the other Blue Zones are quite variable, which reduces the apparent consistency of the C:P ratio hypothesis.

 

Finally, there is the question of how the narrative be influenced in a population consuming all whole food and either practice CR, IF, or both and whom aready have a "healthy lifestyle" overall - presumably so for most of us on crsociety.org.

 

The answer to this may explain at least part of what we are observing in the Blue Zones with respect to variate diets leading to apparently similar or at least high quality outcomes.

 

Other potential explanations for what I dub the "Blue Zone Heterogeneity Paradox" ( BZHP) may be that:

1) not all of the Blue Zone inhabitants have as favorable life expectancy and low burden of disease as it appears ( limitations in the studies ),

2) that genetic and epigenetic factors may be at play ( this is at least partially true for some of the Blue Zones but migrant studies also suggest at least some environmental influences), or that

3) known or unknown non-nutritional environmental factors are more responsible for their better health than we currently attribute.

It would be good to entertain other possibilities too.

 

I am agnostic and would be interested in hearing from others on their reflection including my hypothesis that the low protein ( esp animal protein based on other data ) is the common denominator, with confounding by how satiation influences feeding in ad libitum rodents - the # fat may just not matter so much up to a point (? 30% / 59% / 70% who knows ), provided it is healthy ( e.g. Whole Foods MUFA ). While we are coining names I call this the "Macronutrient Quality and Rodent Satiation" hypothesis or "MQRS." This simply means either or both of these may impact the role of carbs vs fats in an optimally low protein ( especially animal source amino acid profile) diet. Certainly based on these and other studies limiting protein especially animal protein and sulfur/ BCAA AA's seems sensible either way.

 

And also either way genetic and epigenetic factors along with your background of other environmental exposure also may impact the generalization of any of these population level findings on an individual's ideal diet, with factors right down to glycemic load, food matix, what fats/amino acid profiles we are talking about, etc, etc.

 

I thought we had other threads on nutritional geometry and wonder if there is a way to combine with yours. Perhaps incorporating "nutritional geometry" into the title may make it more indexable too? Not sure how or if possible, just a thought - this along with CE,& IF are a couple of the more interesting recent developments in this domain.

Edited by Mechanism

Share this post


Link to post
Share on other sites

Edit: I read Mechanism's post after I posted the following reasonings, but they still apply, basically wondering about the practical applications.

Also am going to read Mitteldorf's observations. In the Simpso et al., 2017 paper I remember no reference to fats, just protein and carbs.

 

Now, in reference to Simpson et al., 2017, I'm not grasping exactly the takeaway lesson.

 

In bugs and mice the optimum protein/carbs ratio for longevity is 1/10. A slightly larger ratio has been observed in rats. Well, what About humans? Does the Okinawans' alleged 1/10 approximate ratio holds for everyone?

 

Then, there is an inherent problem in applying CR (decreasing the caloric intake) and keeping the same C/P ratio of  ad libitum eating. That is, keeping intact the P/C ratio, I might hit a point where I fail to ingest the minimum reccomended daily dose of EAAs (possibly the case with Okinawans). Is this ideal for longevity purposes? Or should I keep the ideal C/P ratio, stopping decreasing calories when my EAAs go below the raccomanded threshold? This would constitute a caloric lower bound for CR.

 

Also, methionine restriction is defined in terms of 65-80% of the standard intake in small animals and rodents. Does that mean that we should really adhere to a lower-than RDI quantity in our regimen? And how about the dangers of potential deficiency, considering that our individual protein and AAs minimum requirement is not known a priori, being the RDI a statistical cautious point estimate of the probabilistic requirement?

Edited by mccoy

Share this post


Link to post
Share on other sites

Mechanism, I cannot change the title of this thread but I inserted a relevant tag.

 

I'm going to read Solon Biet et al., 2014. Apparently a pretty complete paper, and figure 1 summarizes the gist pretty impressively. In mice.

 

1-s2.0-S1550413114000655-fx1_lrg.jpg

Edited by mccoy

Share this post


Link to post
Share on other sites

As an aside, I'm wondering about the following statement:

 

With respect to protein and carbohydrates, plant-based protein has health benefits compared to animal-based proteins (Levine et al., 2014; Pedersen et al., 2013) while complex carbohydrates are likely to be beneficial compared to simple sugars (Suter, 2005).

 

What's the cause of the cited health benefits? I don't think it's just lower Meth and Leu, since in increasing amounts and good variability essential AAs in a plant-based diet can be as high or higher than in an animal-based regimen. Or maybe the above statement is valid in terms of equal total protein.

 

The advantage of complex carbs is obviously related to the lower insulin signal.

 

I'm not sure "at a glance" what the author was getting at, but besides better blood glucose / insulin control, you have to consider that the foods containing complex carbs also contain high quantities of phytonutrients/micronutients and fiber, all of which have strongly documented health benefits through multiple pathways (gut microbiome, immune system health, anti-cancer, neuroprotection, endothelial health, BAT promotion/activation, etc) as well as the fact that the more of these foods you eat, the fewer "harmful" foods (anything that promotes heart disease, diabetes, and/or cancer) you are likely to eat assuming you have met your caloric needs with the complex carb foods you are eating.

Share this post


Link to post
Share on other sites

Al pater, of course the article didn't escape your more than meticulous search and most probably i got there from your list, although I really don't remember, once into the article what was before is forgotten. Maybe i need to start worrying about my short term memory before worrying about the minutiae of nutritional geometry!

Share this post


Link to post
Share on other sites

I'm curious to know how these studies manipulated the macro percentages. I looked but failed to find the specific foods comprising the various diets. I'd imagine it is easiest to manipulate macros using refined products that are relatively isolated: carbs as sugar & starches, fats as refined oils and protein as isolates.

 

But it seems the one point of agreement between the vast majority of diets from Ornish to Atkins is that refined foods are less healthy than whole foods. Which makes me hesitant to place much faith in a study of macro geometry without knowing the details of how the diets were manipulated.

Share this post


Link to post
Share on other sites

Todd,like you say, the studies on rats are interesting but as it is known may fail to be extrapolable to humans.

  1. Type of food used as you say
  2. Different metabolism mice vs humans
  3. Lab creatures vs real life creatures 

We all know the Resveratrol fiasco, it was shown to improve longevity on rats, whereas on humans it failed to exhibit the same effect. I take it now it's sold as an antioxidant.

 

On the other side, in lieu of very costly studies on humans we can only reason on rats, with the proviso that our reasonings may be not extrapolable.

Share this post


Link to post
Share on other sites

I re-read the Simpson et al., 2017 paper, but I don't know know if the results are very useful when applied to humans.

 

They show that in bugs, worms and labmice the ideal (for longevity) protein to carbs ratio is 10%. The ratio is calculated keeping constant the fat intake, usually at its median value.

 

The oldest study on rats exhibits an higher protein to carbs optimum ratio.

 

If I take a typical human diet, keeping stable a fat percentage of 30% in energy, then i set the other 70% of energy at a 10% protein ratio, I come up with 30% fat, 6% protein and 64% carbs (numbers rounded up to integers). Is that the ideal longevity geometry for humans?

But the quantities depend from fat values, if fat is down to 10% then I'm going to have 8% proteins and 82% carbs. In this framework, we can buid up a table liek the following, which follows the same optimum nutritional geometry of lab mice in the Simpson et al., 2017 and Solon Biet et al., 2014 papers. Percentages are ratios on total energy intake, rounded up. 

 

post-7347-0-05645300-1493466097_thumb.jpg

 

 

The table ranges from fat values typical of the Esseltsyn and McDougall diets to those typical of a pure ketogenic diet. We observe immediately that in this optimum geometry (for lab mice) fat steals room to protein and that protein percentages are always lower than 10%. This means that this geometry is impossible to follow in a ketogenic diet and that, even in diets with more moderate amounts of fats, like 30-35%, proteins may be pretty low, like 6% . 

 

My gut feeling is that the above geometry may not be applicable to human beings, although we might conceptually fine-tune it with higher protein to carbs ratios, like 10-20%.

 

The cited studies are formidable in terms of statistical analysis and sheer mass of output data, but the very basic, nagging, legitimate doubt lingers:

 

Is the optimum nutritional geometry in active human beings the same as mice kept in lab containers and fed an artificial diet?

Edited by mccoy

Share this post


Link to post
Share on other sites

Wouldn't the best approach for humans be to first set protein intake in absolute levels (g/kg mass or lean body mass), adjusted to individual needs/goals, age etc. (how much PR? How much desired muscle growth?),  and then find a balance between carbs/fats to fill remaining coloric intake set to maintain a preferred BMI or CR target in accordance to one's preferred diet theory?

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Wouldn't the best approach for humans be to first set protein intake in absolute levels (g/kg mass or lean body mass), adjusted to individual needs/goals, age etc. (how much PR? How much desired muscle growth?),  and then find a balance between carbs/fats to fill remaining coloric intake set to maintain a preferred BMI or CR target in accordance to one's preferred diet theory?

 

Probably so, since we have clinical studies based on human beings here, from which the 0.6 g kg-1 d-1 median minimum requirement has been derived (which equates to the 0.8 g kg-1 d-1 RDA, which is the 97.5%ile of the same statistical distribution)

 

Only drawback is that, the minimum requirement being a random variable, it's not the same for everyone and that it is pretty complex to figure it out. In 95% of the people it spans from 0.4 g kg-1 d-1 to 0.8 g kg-1 d-1. That's not a narrow range. That would mean that, taking a 150 pounds, 68 kg adult (ideal weight), the minimum requirement range (zero nitrogen balance) in lack of activity and ruling out extremes would be: from 27 to 54 grams of protein per day.

 

The question here is: where to start from???

Edited by mccoy

Share this post


Link to post
Share on other sites

I was surprised to find the following making the case FOR BCAA -

 

http://www.lifeextension.com/Magazine/2013/9/New-Longevity-Benefits-of-Whey-Protein/

 

For long time CR adherents, was this really the dominant paradigm then? When did he tides change, and does any narrower scope reasonable controversy remain in this realm of amino acid optimization and restriction?

 

It dates to 2013, and it would have been interesting, I imagine, to be a scientist in the field following the amino acid and longevity story as it unraveled across labs in real time.

 

It goes to show how little we know and makes me ponder what myths we follow today only to be supplanted by better longevity and health paradigms we have yet to suspect or imagine.

Edited by Mechanism

Share this post


Link to post
Share on other sites

Mechanism, from the linked article I could not trace the references. It almost looks like an ad for whey supplements. If research is right, then many bodybuilders who supplement should have a median lifespan increased by almost 10 years. But I wouldn't be surprised if such research has been funded by whey protein manufacturers. Yesterday I saw huge boxes of whey protein sold at the supermarket. Where the whey comes from? China? India? Polluted areas? What were the cows eating? Many times whey is the subproduct of cheese prodution, made out of reconstituted powdered milk. 'Scientist' can toute whatsoever they want, I have strong doubts that such stuff is favourable to longevity. Of course, if that specific strain of mice is a little absorber of BCAAs, or if the human subjects have specific deficiencies, then such supplementation avoids a malnourishment state, increasing median lifespan.

 

I may be wrong but, in lieu of details, that's my first impression.

Share this post


Link to post
Share on other sites

The dubious doctor Mercola is a passionate whey-monger.   (His formula also contains bovine colostrum.)

 

We currently source our whey protein from New Zealand, which is known for its abundant supply of premium pasture-raised cows.  Its temperate climate enables herds to roam freely and feed on white clover and perennial ryegrass year round. Most herds consume 80 to 100 percent of their feed from pasture.  During the winter and other dry periods when pasture growth becomes limited, the cows receive feed supplements such as grass silage, non-GMO maize, barley, fodder crops like beet, kale and swedes, and the much-loved extract from palm kernel waste. The amount of grain in the diet is very small, usually less than one percent. Dairy cows in New Zealand, much like pasture-raised dairy cows in the U.S., typically only see the insides of a barn when it’s time to be milked, between July and November. The remainder of the year they rest out in the pasture and tend to their calves.  This is in stark contrast to factory farm-raised cows who rarely see the light of day.  Once the cows are milked, the milk is transported to facilities in clean, stainless steel trucks where it’s processed into milk, butter, cheese, and whey protein concentrate, a by-product of cheese.

 

"Remember, it's important to avoid excessive protein, but when you need some extra support on your strength training days,  it's great to have a source of  branched chain amino acids with a high amount of leucine, and whey protein has the highest food content of leucine which is an important amino acid to support muscle growth," [Video]

 

http://proteinpowder.mercola.com/Miracle-Whey-Protein.html

 

 

Needless to say, his whey ain't cheap!    ( Other expensive organic and /or "not from cows treated with growth hormone"  whey powders are available as well.)

 

If I were to take a protein powder,  I might go with water-extracted, non-GMO soy protein isolate with plentiful soy isoflavones--but the  anti-soy crowd would surely object.

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Sibiriak, don't be too hard on Dr. Mercola, LOL, he's a decent chap although I had to put him under SPAM, once you subscribe to his site his mails will haunt you day and night. However, the same goes for Dr. Fuhrman, who lags only a bit behind Dr. Mercola. He's another candidate to the SPAM bin. They both have strong commercial interests in the products they sponsor or the activities they organize.

 

Whereas Rhonda Patrick is far, far more discreet.

Share this post


Link to post
Share on other sites

I gree McCoy, I felt that the narrative was unbalanced and poorly documented, with my same concerns regarding objectivity and motivations. I have concerns regarding Life Extension's apparent business model and conflicts of interest. Income streams from "health supplement" is unfortunately widespread in the health website and blog sphere.

 

And so far so I can tell, Rhonda Patrick has been exemplary in this regard, A trend of which I hope can continue. There can be legitimate dilemmas seeking to reach the most potential viewers and having a successful business enterprise for the long-haul in the competitive web based health information domain. So far she seems to be relying at least in part on patron contributions. Her contributions have been quality and substantive and appear to stem from similar personal interest. I am hoping her business model which so far seems to be minimizing potential conflicts of interest will be sustainable and thrives over the long run. By aligning her interest with those of her users, I think she will continue to have the greatest potential to making a positive impact and those of us who share a passion for health optimization.

Share this post


Link to post
Share on other sites

A strange one!

 

Koschei the immortal and anti-aging drugs

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649836/

 

Abstract

In Slavic folklore, Koschei the Immortal was bony, thin and lean. Was his condition caused by severe calorie restriction (CR)? CR deactivates the target of rapamycin pathway and slows down aging. But the life-extending effect of severe CR is limited by starvation. What if Koschei's anti-aging formula included rapamycin? And was rapamycin (or another rapalog) combined with commonly available drugs such as metformin, aspirin, propranolol, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors.

 

 

 
Conclusion: Lessons Learned from Koschei

The creators of fairy tales noticed that the extraordinary longevity is associated with thinness, whereas obese people do not live long. It is not a coincidence that another character of Slavic tales, Baba Yaga the bony leg (kostianaia noga), was extremely old and thin. She cooked potion (зелье), an anti-aging mixture, for Koschei and herself. Now we can compose this mixture by using available drugs. The cornerstone of the formula is a rapalog such as rapamycin. Yet, gerontologists claim that rapamycin cannot be used in humans because of its terrible side effects. This modern tale about side effects of rapamycin might surprise physicians, who have prescribed rapamycin, everalimus to millions of patients worldwide. But practicing doctors do not read basic science papers. Why this misinformation circulates among gerontologists and other basic scientists. May be because Koschei and Baba Yaga were evil and had long curly hair (side effects). Or there are other reasons. I will discuss this in forthcoming article ‘Does mankind deserve rapamycin'.

 

 

babajaga1.jpg

Edited by Sibiriak

Share this post


Link to post
Share on other sites
Mechanism:   ... the macronutrient percentages in the other Blue Zones are quite variable, which reduces the apparent consistency of the C:P ratio hypothesis.

 

 

How variable are the percentages? 

  1. Sardinia, Italy
  2. Ikaria, Greece
  3. Okinawa, Japan
  4. Nicoya, Costa Rica
  5. Loma Linda, California ( Seventh-day Adventists )

"Blue Zones" author Dan Buettner tells us:

 

At the end of the day, [...] I’m not trying to take a scientific stance on whether fat or protein or carbs are better. I will tell you though, that the longest-lived people ate a high complex-carb diet with medium levels of fat and medium-to-low levels of protein. My stance is simply: 'Here’s what the longest-lived people ate over the last century on average, and if you’re interested in health outcomes similar to theirs, you might pay attention to this.  (emphasis added)

 

https://blogs.scientificamerican.com/food-matters/blue-zones-what-the-longest-lived-people-eat-hint-it-8217-s-not-steak-dinners/

 

Mechanism:  I maintain that Dr. Rosedale did not make a very good case in that lecture taken in isolation ( I have not read his formal work ) as why fatty acids must be the primary dietary intake as % of macronutrient to minimize mTOR activation ( yes, fats are neutral and carbs activate mTOR more but earlier in this thread I outline what I perceive to be weaknesses in the limited case he made for this). The contrary diet of mostly carbs in the Blue Zones also speaks for itself and in my mind for this situation empirical data overall trumps other forms of evidence presently available known to me.         (emphasis added)                                                                                                                                                         https://www.crsociety.org/topic/11889-caloric-or-proteic-restriction/page-3?do=findComment&comment=19335    
Mechanism: While short to low-intermediate term studies may suggest acceptability of higher fat diets, the long-term implications are less well studied, and there is some measure of avoidable risk extrapolating surrogate variables indefinitely into the future. One way to address this is to ask how much the %fat varies across blue zone cultures. The presence of blue zone cultures with substantially higher fat content ( that is, substantially higher than for the % at for a prototypical mediteranean diet similar to Sardinia's version at the time) would lend greater credence to a long-term higher % oil diet. In the absence of such cultures I pose the question: would it not be unreasonable, to be conservative, to keep the % calories from oil/fat at or under the percent witnessed by blue zones populations?           (emphasis added)                   https://www.crsociety.org/topic/11661-sensible-diet-and-lifestyle-advice-for-longevity/page-2?do=findComment&comment=16239    
Edited by Sibiriak

Share this post


Link to post
Share on other sites

 

A strange one!

 

Koschei the immortal and anti-aging drugs

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649836/

 

 

That's an entertaining article. The author's narrative makes use of Russian mythology to illustrate some issues in the use of pharmacologycal procedures to boost longevity. His contention is that the use of rapamycin and other longevity-boosting drugs is not so dangerous as some researchers would suggest.

 

Personally, I wouldn't volunteer to make a guinea pig though!

Share this post


Link to post
Share on other sites

 

Mechanism: ... the macronutrient percentages in the other Blue Zones are quite variable, which reduces the apparent consistency of the C:P ratio hypothesis.

How variable are the percentages?
  • Sardinia, Italy
  • Ikaria, Greece
  • Okinawa, Japan
  • Nicoya, Costa Rica
  • Loma Linda, California ( Seventh-day Adventists )
"Blue Zones" author Dan Buettner tells us [sNIP: tht most of them ate relatively high-carb diets].

 

Hi Sirobak,

 

In answer to your question, the following is from Dan Buettner's Blue Zones Solution ( along with his original book on the Blue Zones), in my estimation the best book out there chronicling lifestyles of long-lived cultures.

 

Ikarians 80+ (percentage daily intake in grams)

Greens (17%), Vegetables (20%), potatoes (9%), legumes (11%), grains (1%), pasta (5%), fruit (16%), olive oil (6%), sweets (4%), meat (5%), fish (6%) [ source: Chrysohoou [1]]

 

Okinawans, 1949 (percentage of daily intake in grams):

Rice (12%), other grains (3%), sweet potatoes (67%), other vegetables (9%), legumes (6%), fish, meat, poultry (2%), other foods (1%) [source: Wilcox et. Al [1]]

 

Sardinian Shepards, 1943 (percentage intake in grams)

Vegetables (12%), fruits (1%), legumes (4%), grains (47%), meat, fish, poultry (5%), dairy (26%), added fats (2%), sweets and added sugars (3%). Source: Peretti 1943 as presented in Carbini [1]

 

Seventh-Day Adventists 9percentage of daily intake in grams)

Fruits (27%), vegetables (33%), legumes and soy foods (12%), added fats (2%), nuts and seeds (2%), grains (7%), meat an poultry (4%) dairy (10%), fish (1%), eggs (1%), added sugars (1%).

Source: Jaceldo-Siegl et al. [1].

 

Nicoyans (with note below indicating “in the traditional Nicoyan diet about 80 percent of calories came from carbohydrates, with the remaining 20 percent coming from proteins and fats in about equal measure”): Vegetables (14%), fruits (9%), legumes (7%), grains (26%), meat, poultry, fish (5%), eggs (2%), dairy (24%), added fats (2%), added sugars (11%). Source: Flores and INCAP and ICNNO

 

Although these are not formatted in a manner for direct comparison as categories vary a bit, they give you a sense of fairly low animal products ( except a departure for dairy) for most of them, and low refined sugars ( except a decent amount in Nicoya) . Foods are whole, fresh, locally sourced with lots of plants & no or minimal refined, processed, or packaged goods.

 

On the other hand, % fruit ( see Nicoya and Adventists on higher side), % legumes, % tubers, grains & dairy ( see Sardinia for these latter two, though the dairy is goat & sheep milk & the bread is made traditionally from scratch which may make a difference along with their active lifestyle and possibly genetics) vary quite a bit. Generics are always a question for these studies in geographically isolated populations and while there is evidence for some role, in Okinawa for instance, however migration studies and trend of reversion to the mean following Westernization both point towards substantial environmental and presumably nutritional contributors to longevity & health.

 

[ I indicate original source but don't have full citation on hand, which can be found in Buettner's book ]

A Summary of the foods that make up the individual diet can be found here:

1) http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=55512( overview) , http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=55662 ( Okinawa), http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=55710 (Sardinia), http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=55863 (Nicoya) though I did not see on quick pass the other Blue zones.

 

A very nice 1 page summary of overall commonalities can be found here: https://www.bluezones.com/wp-content/uploads/2015/06/Blue-Zones-Food-Guidelines-2015.pdf

 

and of his Blue Zones solution book here: http://www.chewfo.com/diets/the-blue-zones-solution-by-dan-buettner-food-list-what-to-eat-and-foods-to-avoid/

 

NPR did a nice job on the overview: http://www.npr.org/sections/thesalt/2015/04/11/398325030/eating-to-break-100-longevity-diet-tips-from-the-blue-zones

 

and Wikipedia has a nice Venn Diagram of some commonalities: https://en.wikipedia.org/wiki/Blue_Zone

 

None of these are a replacement for Dan Buettner's book which I highly recommend: https://www.amazon.com/s?field-keywords=blue+zones+solution

Edited by Michael R

Share this post


Link to post
Share on other sites

Mccoy,   I just noticed that the author of the "Koschei the Immortal" article, M.V. Blagosklonny,  is co-author of another article you posted about:  "Gerosuppression by pan-mTOR inhibitors."    https://www.crsociety.org/topic/12141-rapamycin-old-stuff-now/?do=findComment&comment=20564

 

 

https://en.wikipedia.org/wiki/Mikhail_Blagosklonny

 

Rapamycin and aging

Blagosklonny has formulated a hypothesis about the possible role of TOR signaling in aging and cancer and proposed using rapamycin, a popular cancer drug as a possible treatment for life extension.[2] He is considered one of the most passionate advocates for rapamycin in longevity research.[3]

 

Editorial activities

Blagosklonny is editor-in-chief of Aging,[4]Cell Cycle,[5] and Oncotarget.[6] In addition, he is associate editor of Cancer Biology & Therapy[7] and a member of the editorial board of Cell Death & Differentiation.[8]

The reviewing process employed by Oncotarget has been criticized by Jeffrey Beall,[9] who also included Oncotarget and Aging on his list of "potential, possible, or probable predatory scholarly open-access journals"[10] in July 2015.[9] Further reports on Beall's blog suggest that the substandard peer review processes for these journals are used by their respective editor-in-chief to entice prospective authors to include references to Blagosklonny's own publications in their articles (following the peer review), thereby raising his personal impact factor.[11]

 

Blagosklonny has published over 270 papers in peer-reviewed journals with over 25,000 citations, giving him an h-index of 83.[12]

 

(Blagosklonny [благоскло́нный],  btw,  in Russian means "inclined to be good" , "benevolent",  "kind".)
 

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now

×