Abstract
…The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain. Evidence concerning this possibility is detailed…Results from a number of sources refute both the theory and effectiveness of the carbohydrate-insulin hypothesis. Instead, risk for obesity is primarily determined by total calorie intake.
This is one of those pay-to-publish articles. It’s not a study, it’s an opinion piece (probably being kind, there) from two flunkies at the ‘Tudor Bompa Institute.’ Tudor Bompa - smart guy, great athletic coach, but he’s in his late 80s now and the "Institute’ is just trying to sell stuff.
If the underlings want to be a “published author,” they can get stuff put up for $975 or $800 if they want to pay to become “members” (presumably worth it if they want to “publish” a lot of stuff).
Or, if you can convince them it falls within “Rapid Reports, Case Studies in Neuroscience, and Case Studies in Physiology,” then it’s only $600/$495. 
Why only carbohydrates? (that is, if your looking at it from a longevity angle?)
Portion size of all three calorie categories? (according to concentrated density if any?)
When do we eat said portion size?
How long do we wait to eat next portion size?
The prospect of higher protein intake does not look so good from a longer life-span or quality of health or life advantage?
Footnotes:
[1] “…Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. …” …More
[2] “…Aging and dietary restriction interact through partially overlapping mechanisms in the activation of the conserved nutrient-signalling pathways, mainly the insulin/insulin-like growth factor (IIS) and the Target Of Rapamycin (TOR). The specific nutrients of dietary regimens, their balance, and how they interact with different genes and pathways are currently being uncovered. …” …More
[3] “…Cutting calories through dietary restriction has been shown to lower cholesterol, improve insulin sensitivity, and even prolong life in mammals. Now, new research shows that, at least in mice, low protein, high carbohydrate diets can provide benefits similar to those obtained with calorie restriction. …” …More
[5] Methionine Inhibits Autophagy and Promotes Growth by Inducing the SAM-Responsive Methylation of PP2A
[6] The fasting function:
F (x,y,z) (AKA fasting is a function of x, y, and z)
x = the amount you restrict calories (100% = > full calorie restriction)
y = the duration of the fast
z = the frequency at which the fast is repeated …More
[7] “…Methionine is a nutritionally essential, sulfur‐containing amino acid whose low level in plants diminishes their value as a source of dietary protein for humans and animals. Methionine is also a fundamental metabolite in plant cells since through its first metabolite, S‐adenosylmethionine (SAM), it controls the level of several key metabolites such as ethylene, polyamines, and biotin. SAM is also the primary methyl group donor that regulates different processes in plants. Despite its nutritional and regulatory significance, the factors regulating its synthesis and catabolism in plants are not fully known. …” …More
[8] “…The Orentreich group has shown unequivocally that both rats and mice maintained on a methionine-restricted diet live significantly longer than those fed normal chow (Orentreich et al. 1993; Zimmerman et al. 2003; Miller et al. 2005). Moreover, these methionine-restricted rodents not only show greater activity but also prolonged good health with both a lower incidence and delay in age-onset of cancer, cataracts, inflammation, and insulin insensitivity (Miller et al. 2005; Stone et al. 2014; Sinha et al. 2014). Although the low methionine plant-based naked mole-rat diet is supplemented with both a protein-rich cereal and the high protein content of digested microbiota in fecal samples, naked mole-rats have low serum levels of methionine and other components of this pathway and, similar to dwarf mice (albeit profiled from liver tissue and not plasma), share many common traits with methionine-restricted mice including resistance to cancer as well as enhanced stress resistance (Brown-Borg et al. 1996; Buffenstein 2005). It is possible that these shared traits of similar perturbations in circulating methionine metabolites reflect that methionine metabolism is an integral modulator of both health and life span (Uthus and Brown-Borg 2006; Brown-Borg and Buffenstein 2017). These metabolite abundance differences observed between naked mole-rats and mice were found to resemble that of hibernating ground squirrels and rats subjected to dietary/amino acid restriction. All these rodents possess several traits in common such as lower body temperatures, low thyroid metabolism, low insulin levels, and reduced metabolic rates (Buffenstein et al. 2001). These findings suggest a possible link between the downstream effects of a lower metabolic rate, altered protein metabolism, and increased life span. In addition, the significantly lower levels of specific amino acids, most notably, methionine, serine, aspargine, and aminoadipate, and energy metabolites (hydroxybutyrate, diphosphate, nicotinamide) in hibernators (D’Alessandro et al. 2017) are correlated with body temperature during torpor and may also contribute to the lower body temperature and thermal lability of both dwarf mice (Hunter et al. 1999; Gesing et al. 2012) and naked mole-rats (Buffenstein and Yahav 1991a). Both hibernating squirrels and dwarf mice also exhibit signs of increased cytoprotection. NRF2 protein levels are constitutively increased not only in the naked mole-rat, but NRF2-signaling levels are also increased in dwarf mice (compared to wild-type littermates) and hibernating squirrels (compared to fully aroused squirrels) (Pier Jr et al. 2008). This mechanism is hypothesized to prevent the accumulation of oxidative damage that can potentially contribute to disease states including cancer and rapid aging. With respect to humans, a study looking at the effect of age on metabolite levels reported that in young adults, the levels of essential and nonessential amino acids, urea, ornithine, polyamines, and oxidative stress markers (e.g., hippurate) are lower than in older adults (Lawton et al. 2008). These low metabolite levels are supportive of the youthful naked mole-rat metabolomic profile when compared to mice. Albeit, given the variability in human phenotypes due to many uncontrolled environmental effects, as well as co-factors such as race, sex, body mass index (BMI), and health status, this analogy warrants confirmation from larger and better-controlled studies. In summary, we report here that the unbiased and comprehensive metabolomic analysis of differences in abundances of circulating metabolites between naked mole-rats and mice surprisingly reveals commonalities in amino acid profiles with both hibernating and methionine-restricted mammals. These data also concur with findings from Ames dwarf mice and caloric restricted mice and human studies in which people with a youthful phenotype have lower levels of amino acids, creatine, and tricarboxylic-acid metabolites than older people. Collectively, we speculate that low circulating levels of amino acids may be a metabolic signature in organisms that exhibit prolonged longevity. It is important to emphasize that these are still ongoing studies with many key metabolites currently unidentified. As we progress and begin to identify unknown metabolites, it is likely that additional novel mechanisms that contribute to the exceptional longevity of naked mole-rats will be elucidated. Finally, the observed similarities between experimentally manipulated long-lived mice and the naked mole-rat, including increased body fat, increased cellular stress resistance, increased cancer resistance, and now similar metabolomic signatures supports the possibility of convergent mechanisms contributing to prolonged life span. …” …More
[9] Role of Choline and Methionine Antagonists in Metabolism, Published: 01 May 1958
[10] “…Substantial evidence indicates that as much as half of the life-extension benefits of CRAN (Calorie Restriction with Adequate Nutrition) are due to restriction of the single amino acid methionine. In a study of rats given 20% the dietary methionine of control rats, mean lifespan increased 42% and maximum lifespan increased 44% [THE FASEB JOURNAL;Richie,JP; 8(15):1302-1307 (1994)]. Blood glutathione levels were 81% higher in the methionine-restricted rats at maturity, and 164% higher in old age. Long-lived Ames dwarf mice have an enhanced methionine metabolism that increases tissue glutathione (GSH) [MECHANISMS OF AGING AND DISEASE; Uthus,EO; 127(5):444-450 (2006)]. Neither the long-lived growth hormone receptor knock-out mouse nor the Ames dwarf mouse show additonal lifespan extension with methionine restriction, suggesting that stimulation of protein synthesis by either methionine or growth hormone shortens lifespan [AGING CELL; Brown-Borg,HM; 13(6):1019-1027 (2014)]. …” …More
Huh? … carb restriction doesn’t work?!
Okay, time to stop. 
(… or perhaps we need to further clarify what “work” means? 
)
That’s from the SAD forums…
Here at Ketogenic Forums, things work differently…
Do you have some evidence to back up this claim? Is the American Physiological Society a reputable scientific organization? If not, please provide evidence to the fact. Is the American Journal of Physiology-Endocrinology and Metabolism a reputable science journal? If not, please provide evidence to the fact. Do they publish junk science? If so, please provide evidence to the fact. Do they not peer review submissions for publication? If they do not, please provide evidence to the fact.
The paper includes 36 references. Can you point out that all, many, some or even any of these have been cited incorrectly or irrelevantly? This paper has been cited 9 times by others. Do you have evidence that these citations are incorrect or misguided?
I am no fan of CICO Theory nor diets based on it. So I would be very happy to discover what you claim is true and this study and many/most of the others that this study cites to support its conclusions are all mistaken. It’s going to take more, however, than the association of one of the authors with Bompa to discredit this. Thank you.
It’s definitely pay-to-publish. This is easily verifiable for anybody. If you want to find “stupid stuff,” you will find it at such websites.
It’s like Forbes or Harvard Health. Used to be, these were serious and respected. It’s most surprising for Harvard Health - how are they even allowed to use that name? Harvard Medical School is still top-notch, but over the past 3 or 4 years I’ve seen stuff published under ‘Harvard Health’ that wouldn’t stand up to the most cursory examination.
I suspect the body tries to use everything it gets, waste nothing (I wonder what the body does with amino acids from digestion it can’t convert to new proteins or repairs). The obvious benefit I get from low carb is appetite control. After several years eating, at any particular moment, is much less important than it used to be. These days my annual cheats can be counted on the fingers of one hand. Losing weight hasn’t been a pressing issue for a while but would be easy to do if I reduce calories for a while. What I prefer is to lose weight by eating nothing one day a week.
The Harvard Department of Public Health was established with money from the sugar industry, for the purposes of training researchers to work for the sugar industry. Its ties to the nutritional establishment (i.e., Ancel Keys and his friends) are legendary and numerous.
We’re still missing something. We have the hormone hypothesis researchers finding significant ‘metabolic advantage’ from macronutrient sources of calories (fat vs carb) and the CICO/anti-hormone researchers finding insignificance for same. This is like Bizarro World.
Is this just due to bias or cherry-picking data because ‘the sugar industry’ funds x and the ‘Metabolic Truth Foundation’ funds y?
Yes.
As Taubes mentions, he got into writing about nutrition science because several of his physicist friends told him that if he thought there was a lot of bad physics going on, he should see just how much worse nutrition science was in comparison.
Taubes does also point out, however, that nutrition science is extremely difficult to do rigorously and well. The experimental subjects (human beings) live too long and are hard to control, double-blind studies are almost impossible to conduct (in almost every case), and the costs involved are astronomical. (Not to mention that studying nutrition isn’t nearly as sexy as running a cyclotron.)
Also, it doesn’t help that the field of medicine, while scientific in many ways, is basically a hierarchically-run enterprise, in which acknowledged experts are held in reverence, whereas any snotty young physicist knows that a sure path to the Nobel Prize would be to do for Einstein as Einstein did for Newton.
We know there has been peer-censorship, threats against credentials, deception, corruption and hush money in the research about refined sugar but that does not mean sugar is entirely “bad?”
I wish my doctor would get up on the table throw a fit and scream at me as loud as he can “don’t eat so much of it?“ and slap me on back of the head…lol
The body doesn’t store much protein at all - a tiny bit in circulation? Excess can be used for energy, but most of the time doesn’t need to be. It can be made into fat or excreted; doesn’t high nitrogen in urine often indicate that excretion’s going on? I don’t know what else - good question.
Yeah, we are definitely usually efficient and try and use it all. I look at my stomach in the mirror and say, “Well aren’t you a bloody efficient little (big) bugger…” 
Gaah! 
Great answer but it’s kind of enraging, isn’t it? :: pounds head against wall ::
There are things like The Nurses’ Health Study, often mentioned as the “Harvard Nurses’ Study.” In the third iteration now and with almost 300,000 women involved, valuable stuff. Associated are ‘Harvard Medical School’ and ‘Harvard T.H. Chan School of Public Health.’
So then we see “The Harvard Department of Public Health.” 
Most people are going to think it’s all the same. The SUGAR INDUSTRY! 
It’s like in the other thread you began - you have to have the dietary/metabolic context and a complete picture.
Well indeed. Yes, sometimes it does work like that. So, what’s the complete picture and the dietary/metabolic context there? Sometimes calories in and out is a determinant of weight. You don’t think all that’s referenced was outright faked, do you?
But it does not HAVE to be that way. Somebody from the ‘Tudor Bompa Institute’ writes something - that doesn’t mean it’s the final word, period. This is why I was talking about “pay-to-publish.” It’s not uncommon to see BS via that method.
The Tudor Bompa stuff is clearly biased and focused on cherry-picked information. They are trying to imply that it’s always that way.
Tudor Bompa is NOT saying that. If anything they are saying the exact opposite.
That also is not true. CICO doesn’t rule out hormonal effects. By definition, “calories out” can change. Nobody’s position is that energy expenditure has to remain constant.
Again, let’s look at the dietary/metabolic context and the complete picture. Let’s see what is happening, let’s see what the situation really is, to begin with.
The truth about what Tudor Bompa says is that sometimes it’s valid. The obvious point is that it’s not always so.
Maybe not in your definition…
There is a labile pool of amino acids, but you are right; it is not very large. The body has no way to store amino acids in bulk, as it has for fatty acids. I once read an article that claimed there was some simple reaction amino acids can undergo that allows the result to be stored, but again, the quantity that could be stored was small, if I read and remember the article correctly. Nor does the body seem to “store” amino acids by turning them into lean tissue (I suppose it could in theory, but it doesn’t seem to do so in practice).
Deaminated amino acids aren’t all automatically made into fat, I don’t believe. If I recall rightly, some amino acids lend themselves to be converted more readily into glucose, while others can more easily be converted to a fatty acid, and still others can easily be converted into either. The body can handle the ammonia resulting from deamination without too much trouble, unless the quantity of amino acids to be disposed of is too large for the uric acid pathway to be able to cope. That way lies ammonia toxicity, and I believe Richard once calculated that ammonia toxicity becomes a real risk when dietary protein reaches 3 g/kg LBM or so.