Carbs: Low vs. Lower



This was met with much backlash from the low carb cavalry, because, well, if low is good then lower must be better

I’m not anti-keto; but I’m not anti-science.  FACT.


“…some people are not genetically equipped to thrive in prolonged nutritional ketosis.” –Peter Attia

So, we have this: Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets (Johnston et al., 2006)

It’s not a bad study.

For more, head over to Patreon!



body fat


calories proper


Become a Patron!




Be Sociable, Share!
  • Excellent post Bill! A LOT of people would do well to read this and take the points on board!

  • FreedomFromOurselves

    There is still too much protein in that KLC diet to get people in Ketosis to actually USE the ketones for energy. The KLC diet listed may have had people burning glucose from gluconeogenesis. Search for Stephanie Person on You Tube for more on this subject.

    • It wasn’t too much protein because they WERE in ketosis! It was a modest degree of ketosis (~0.5 mM), but ketosis nonetheless.

  • I believe I am seeing a shift where, when I was fat I could stick to the very low carb high fat sort of diet and lose lots of weight, but now if I want to lose weight I have to have less fat and- consequently- more carbs. It seems like the closer you get to your target (and I have been at my target in weight terms, but working on body comp.) the more calories seem to matter. I also started working out, which seems to increase the drain on my glycogen stores.

    • Food intake in obese IR patients on LC declines effortlessly, so watching “calories in” matters less… calories still matter, but the need to monitor them doesn’t…

  • Oliver

    That’s okay with me. I do keto for the benefits of the ketones themselves such as HDAC inhibition, autophagy, etc. Everyone in my family dies of cancer. It’s a fate I wish to avoid if I can.

    • word.

      • Diana

        Where does the belief that ketones prevent cancer come from?

        • CynicalEng

          It’s the reduced glucose starving the cancer behind that view I think.

          • Diana

            ” reduced glucose starving the cancer”???

            What a joke.

          • CynicalEng
          • Diana
          • Beta Hydroxybutyrate

            Diana, the study you posted was cited by the study CynicalEng posted here: “A recent report by Listanti, et. al proposed that tumor-associated fibroblasts produce ketone bodies for cancer cells to use as fuel [68]. The authors have previously published several papers with similar findings [69], [70], [71]. In these studies, the authors created immortalized fibroblasts which were altered to overexpress rate-limiting enzymes in ketone body production, and co-cultured these cells with human breast cancer cells altered to overexpress enzymes involved in ketone body utilization. While this phenomenon may occur in the genetically altered culture system used by the authors, there is no evidence that this occurs naturally in cancer cells in vitro or in tumors in vivo. On the contrary, the literature as a whole strongly suggests that cancer cells cannot effectively use ketones for fuel. As described, most cancers do not express the SCOT enzyme which is necessary for ketone body utilization [65], [66]. Several studies have reported a deficiency of cancer cells to metabolize ketone bodies in vitro [24], [25]. Furthermore, it is widely accepted that ketone bodies are produced nearly exclusively from fatty acid ?-oxidation in the liver. There is no known metabolic pathway by which fibroblasts can produce ketone bodies from glucose.”

            Furthermore, if you want to prevent cancer, reducing ROS and DNA damage is the way to go. Ketones are pretty darn good at accomplishing that.

          • Diana

            Yes, ketones from the liver, I agree. But what is not clear to you?

            “Here, we have used MCF7 cells as a second independent breast cancer cell
            model, to study the effects of ketones and lactate administration on
            gene expression. Treatment of MCF7 cells with high-energy metabolites
            (such a L-Lactate) is sufficient to stimulate mitochondrial biogenesis,
            as reflected by a dramatic increase in overall mitochondrial mass per
            MCF7 cancer cell.
            Interestingly, we show that ketones and lactate both increase the
            transcriptional profiles of genes that are associated with “stemness”
            (neural, embryonic, and hematopoietic stem cells). Thus, the metabolic
            use of ketones and lactate could “fuel” the cancer stem cell phenotype,
            which may be responsible for promoting tumor growth and metastasis. In
            accordance with this notion, we show that the ketone- and
            lactate-induced “gene signatures” (generated using the luminal A-like
            MCF7 cell line) predict recurrence, metastasis, and reduced overall
            survival in the most common form of human breast cancer [the ER(+)
            luminal A subtype].”

            Second, ketones as prevention, via reducing ROS? Have you ever hear of methylglyoxal on ketogenic diet?

            And third, where are the successful cases? Slowed down, perhaps, but cured?

          • Beta Hydroxybutyrate

            This study shows how much ketones protect against ROS. They took two groups of mice and infused one group with ketones. Then they poisoned them with paraquat, which is a powerful pro-oxidant. Protein carbonylation was 54% lower in the ketone group than in the control group.

            They also evaluated a maker of oxidative stress in these mice, 4-hydroxynonenal (4-HNE). 4-NHE is a product of polyunsaturated lipid degradation and accumulates in response to oxidative stress. The control mice had a three-fold increase in 4-NHE, indicating high levels of oxidative stress. This increase was completely suppressed in the ketone group.


            Have you heard about advanced glycation end products or AGEs? Ketones inhibit the formation of those as well.


            In this pilot study, cancer growth either stopped or started to shrink in over half the subjects. Those subjects had the highest ketone and lowest insulin levels.


            If you really want to see cancer being annihilated, take a look at the following video. When the researchers combined radiation with the ketogenic diet, cancer was eradicated. The ketones protect the healthy cells from the radiation while making the cancer cells more vulnerable somehow. They were cured. Even after returning the animals to a normal diet.


            Lifespan studies have also finally begun. So far in worms ketones have been found to extend lifespan. Markers for diseases such as Alzeimers and Parkinsons were also reduced.


          • Diana

            I really appreciate you discussing this, though this post is not devoted
            to ketones and cancer. But someone mentioned long term KD as
            preventative (it seems even Dr. Lagakos agrees), so I needed to react.
            There is surely a beneficial effect of protective starvation signalling,
            during real fasting. Even Dr. D’Agostino mentions that too. My concern
            is if long term nutritional KD has the same effects. And as I said,
            cancer can adapt to other fuel, it just takes its time. Even Dr.
            Seyfried has witnessed this in his mice studies with tumor xenografts.

            first study you post has nothing to do with the point: is long term KD
            working the same way? In my opinion it is rather showing the sudden
            stressor effect of increased ketones upregulating the stress response,
            and in this way protecting against the other stressor (the poisonous

            The second study you show doesn’t answer my point at
            all. Methylglyoxal appearing on KD induces formation of AGEs as well.
            Didn’t you know?

            The third paper: “Ten subjects completed 26 to
            28 d of the study diet without associated unsafe adverse effects.”
            Twenty eight days. We don’t know what happened next.

            And also, from the full:

            patients with advanced cancer were recruited. For reasons unrelated to
            the intervention, two patients discontinued the study in less than 14 d
            and therefore were not evaluated. Of these two patients, one withdrew
            because of symptomatic chest wall disease on day 2 of the diet,
            requiring hospitalization and chemotherapy; the second patient withdrew
            after 1 wk because of clinical depression. The remaining 10 patients
            were included in the results; of these, five patients completed all 28 d
            of the trial, one patient completed 27 d, and four patients completed
            26 d of the dietary intervention.

            It is important to note that
            all 10 study participants spontaneously decreased their caloric intakes,
            nine of whom lost weight, despite our best efforts to maintain a stable
            weight by encouraging increased food consumption. Participants showed a
            mean 35% caloric deficit and a 4% weight loss, raising the question of
            whether caloric restriction played a role in our findings.”

            therapy works best, by hitting more weak points at once, or by pulsing. No dispute abou that. Again, no long term magical effect by ketones alone.

            last: HDAC inhibitors: ketones are not the only common metabolite with
            HDAC inhibiting properties. Check butyrate. Best to switch between these
            two, IMO.

          • Beta Hydroxybutyrate

            Hello Diana,

            That first study wasn’t the best example since it was indeed acute exposure as you pointed out. Here are a couple that aren’t:

            “Isolated hippocampal mitochondria from KD-fed rats showed functional consequences consistent with the improvement of mitochondrial redox status i.e. decreased H2O2 production and mtDNA damage. Together, the results demonstrate that the KD up-regulates GSH biosynthesis, enhances mitochondrial antioxidant status, and protects mtDNA from oxidant-induced damage.”


            This next study shows evidence of protection from ROS in humans:

            “Urine 8-iso PGF2?, a free radical-catalyzed product of ARA, was significantly lower than baseline following CRD-UFA (?32%). There was a significant inverse correlation between changes in urine 8-iso PGF2? and PL ARA on both CRD (r = ?0.82 CRD-SFA; r = ?0.62 CRD-UFA)”

            If arachodonic acid is being protected from free radicals, it’s more than likely that everything else is too – including DNA and mtDNA. If there is less damage to DNA, as in the rats, the risk of carcinogenic mutations arising should decrease as well. Wouldn’t you agree?

            I’m not as concerned with cancer cells being able to adapt to different fuels. At this point, I’m more concerned with prevention. I wouldn’t stop using a seat-bealt, for instance, merely because people who wear them can and do still die while wearing them.

            As for Methylglyoxal, I remember reading about it in what seems like a decade ago. That’s why I posted the study showing that BHB inhibits AGE formation. Avoiding methylyoxal didn’t help the control nematodes in the longevity study after all. I know we aren’t nematodes but still, are AGEs any less toxic to their tissues?

            Regarding butyrate, I can see how it might help the liver and colon but I don’t see how blood levels could go very high on diet alone. Butyrate is shunted to the portal vein, like MCT, and delivered directly to the liver. What’s not used by the liver itself gets converted to ketones. What I found interesting though is that the colonocytes of rabbits will actually do the conversion of butyrate to ketones themselves. I wouldn’t be very surprised if human colonocytes did the same.

          • Diana

            Hello Beta Hydroxybutyrate

            The first
            study you post in reply: “We sought to determine whether the KD improves
            mitochondrial redox
            status. Adolescent Sprague-Dawley rats (P28) were fed a KD or control
            diet for 3 weeks and ketosis was confirmed by plasma levels of
            beta-hydroxybutyrate (BHB).” Three weeks, too short again. I don’t
            dispute beneficial effect of KD as a very short term intervention. But
            still, I think real fasting would be better. And I am worried of the
            long term use.

            The second paper you link (and I have
            nothing against saturated fat if that was your point) says: “The other
            remarkable finding in our previous investigation was a
            significant decrease in inflammatory markers despite a marked increase
            in plasma arachidonic acid (ARA) [7].

            The metabolic intermediates in the production of ARA were decreased
            suggesting that synthesis was not increased. We proposed rather that the
            increase was due to better preservation of ARA.” That means the author
            speculate only, what happens to ARA. Might be another reason why it is
            there…. related to the microbiome change. Not really good news.

            Regarding methylglyoxal, start perhaps here:”
            Ketosis Leads to Increased Methylglyoxal Production on the Atkins Diet”

            who is talking blood levels? It is rather about GPR receptors. This
            way butyrate signalling exerts other effects than ketones! And that is why I think you need both. What is your butyrate level, if you follow KD? (stool test)

          • Jethro Bodine

            Could you please provide details of what you mean by “real fasting?”

          • I should probably wait for Diana to reply, but in the meantime, I think she’s probably referring to some sort of intermittent fasting regimen.


          • Diana

            “what you mean by “real fasting?”

            That happens when you kind of, don’t eat anything at all, for some time.

          • Thomas Hemming Larsen

            I think he meant that he believes that glucose feeds cancer cells. Whether that’s true or not I can’t comment on.

          • Diana

            Cancer cell will happily metabolise not only glucose, but also lactate, glutamine
            etc., and unfortunately ketones too. It just needs some time to adapt to other fuel
            source. That’s why the “prolonged survival” only, in the title of the
            paper CynicalEng linked. Ketones can provide a lot of energy too, cancer is not
            so stupid to ignore it.
            The paper I linked is called: “Ketones and
            lactate increase cancer cell “stemness”, driving recurrence, metastasis
            and poor clinical outcome in breast cancer”.

          • Thomas Hemming Larsen

            As I said, I was only trying to clarify. You can take the discussion with CynicalEng.

          • The Warburg Hypothesis is that tumors are actually obligate users of glycolysis rather than mitochondrial respiration.


          • Diana

            Alas, only partly true. Ever heard of metabolic reprogramming (reversible switch between fermentation and oxidative metabolism)? Once again, cancer is not stupid. It is actually smart.

            “Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies”

            “The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression”

          • Jack Kruse

            Hypothesis it is. There is another more plausible explanation.

            A little known fact about a Warburg metabolism: everyone focuses in on the glucose aspect of Warburg’s findings, but if you read his original papers he also found a lot of ammonia released simultaneously to glucose use. Why did he find that? Ubiquitin up regulation creates excess protein turnover, and this leads to a lot of ammonia and Reactive Nitrogen Species. When nitrogen gets oxidized, this means electrons are taken away from its molecular structure. When this happens mTOR is activated. This is why mTor expression is a problem for longevity and for “current beliefs.” NAD+ drops and NADH rises. You need to be smarter than they currently are. When ubiquitin is coupled to metabolism properly carbs actually act as a braking mechanism to the PER 1 and PER 2 clock genes. Remember every mammal on this planet has a clock gene before every somatic gene. So when these two cycles are uncoupled (mostly by bad light) you should expect excess glucose uptake to slow the PER 1 and 2 mechanism! The real issue is not the glucose…… is the ammonia and protein tied to mTOR and altered ubiquitin. This is also bored out in the cancer literature but no one really understands ubiquitin well because it is driven by light cycles and dark periods and not foods. We lose the carb brake mechanism when circadian cycling is no longer yoked giving us the false impression carbs are a cancer’s potion. The key is looking at superoxide levels and ubiquitin marking and the cell’s redox potential to sort this out.

          • Jack Kruse

            We need more data and cellular markers tell us what a method of NAD+ enhancement is actually doing in our cells to enhance health and possible longevity. Ketosis enhances NAD+ but I have a sense that will only work when Sirt 1 and 6 are properly managing ubiquitin. I have a sense other exogenous NAD+ strategies may lead to harm in longevity and especially oncogenic states. The environment of the cell is the key driver in my mind based upon what the research shows.

          • there has been a lot of chatter about niacin analogs in boosting NAD+ in this context…

            seems overly simplistic at this stage… like, circadian biology is upstream of NAD+ rather than the inverse? (or something like that)


          • Regarding the ammonia, that’s interesting. Probably leads to insulin resistance and ultimately higher blood glucose levels -> more fuel for the tumor.

          • Diana

            Re ammonia – you start paying attention finally. It is in a proliferating mode, it needs building blocks (nitrogen etc.) and suitable working environment (pH). See for instance:

            CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4.
            “Cancer cells rely on glycolysis to maintain high levels of anabolism.
            However, the metabolism of glucose via glycolysis in cancer cells is frequently incomplete and results in the accumulation of acidic metabolites such as pyruvate and lactate. Thus, the cells have to develop strategies to alleviate the intracellular acidification and maintain the pH stability. We report here that glutamine consumption by cancer cells has an important role in releasing the acidification pressure associated with cancer cell growth. We found that the ammonia produced during glutaminolysis, a dominant glutamine metabolism pathway, is critical to resist the cytoplasmic acidification brought by the incomplete glycolysis. In addition, C-terminal-binding protein (CtBP)
            was found to have an essential role in promoting glutaminolysis by directly repressing the expression of SIRT4, a repressor of glutaminolysis by enzymatically modifying glutamate dehydrogenase in mitochondria, in cancer cells.”

            A proposed role for glutamine in cancer cell growth through acid resistance
            “Cancer cells exhibit a greatly increased level of aerobic glycolysis with accumulation of lactic acid, a phenomenon known as the Warburg effect. Apparently, survival of cancer cells requires an elaborate system for acid resistance. L-glutamine (Gln) has long been known to be essential for cancer cell growth, which is generally thought to relate to the nutritional value of Gln as carbon and nitrogen source. On the basis of our recent finding that Gln provides acid resistance for E. coli through release of ammonia, we hypothesized that the primary role of
            Gln in cancer cells is to fight acid, rather than provide nutrition, through enzymatic deamidation. In this letter, we provide preliminary experimental evidence that supports this hypothesis. We demonstrate that Gln helps cancer cells survive acidic stress, which is compromised by inhibition of specific glutaminase activity.”

          • Jack Kruse

            I don’t think so Bill…….I think it is a beacon and not a fuel source. Ubiquitination is a light driven process and not a food driven one! Light signaling is present 24/7 and food signaling is not……..This is why ancestral health and biology miss the boat in my opinion. It is also why ubiquitin sits upstream of the cell cycle and metabolism.

          • Jack Kruse

            The Earth’s environment is a 24/7 factor Bill. Every single minute of the day we have the chance to be exposed to various spectrums of light or total darkness if we do sleep correctly. Compare that to eating. Maybe we spend an hour total eating meals. Wonder which matters more? Food is not the man driver. It effects us only when we eat. The rest of the time light/darkness drives life. Time to ditch the dogma. Plants have no need for food electrons because they get all electrons from the sun and the Earth’s magnetic field. They are alive as we are, moreover, and very germane, they use the DC current to regenerate as all animals do. This means how they make energy is coupled to animal metabolism is a very deep way. Regeneration pathways are identical in both even today. Wakefulness has the DC current and it disappears in sleep. Moreover, plants also regulate their photosynthetic balance to the presence or absence of light by altering the components involved in photosynthesis in quantum fashion. All plants are coupled to animal life by way of he CO2 and O2 cycles. Photosynthesis operates most efficiently when the rate of CO2 diffusion into the leaf matches the biochemical capacity of the leaf to fix CO2. This also varies day to night. We do the same things using water and O2 reduction in a mitochondria. Plants do it by altering stomatal conductance of their pores. This is how C3, C4 and CAM photosynthesis react to different environments to water and light inclination. Light dramatically alters how electrons are handled in plants and animals but too few people in biology see the homology. Read Life at the Edge Bill by Jim Al Khalili. You’ll find even in plants this nitrogen issue persists. In long lived leaves, they typically have low nitrogen concentrations and a very low photosynthetic capacity. This is why the Warburg metabolism exists in animals too, who are exposed to chronic fake light…… is not a fuel source. Fake light exposure anytime, especially, night time increases ubquitin action. This is why ammonia shows up. It is a circadian mismatch looking for a brake that no longer can work when ubiquitin is uncoupled by blue light and fake light.

          • Jack Kruse
          • Diana

            Jack Kruse is right, this time. Light rules, ubiquitin matters, and we are partly plants. That’s why UV-activated auxin (a plant hormone) kills cancer cells.

          • Bruno

            Diana – Did you know that circadian timing also effects the outcome of cancer treatments?

          • Diana

            Bruno – yes I am aware, thank you. Though denied by many oncologists. Patients beware…
            Inflammation cycle in cancer often oscillates too.:

            CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?


            “Single measurements of CRP or L-CRP have previously been used to correlate with the risk of certain cancers, prognosis or cancer recurrence, as mentioned above, and occasionally these have been
            repeated weeks or months apart to determine any persistence or trends in
            CRP levels. However, we have examined L-CRP in the serum of patients with advanced melanoma and ovarian cancer, measured serially 1-2 days apart,
            and identified an apparent ‘cycle’ in the CRP levels. Serial L-CRP measurements were plotted to rise and fall in a cyclical manner over time. These immune oscillations were dynamic in the cancer patients studied, revealing an apparent cycle, with a periodicity of approximately 6-7 days, in most situations. The amplitude appears to increase and decrease in response to the intensity of overall inflammation and disease activity.”

          • Jack Kruse

            LOL, this time. I ve been very coy here Diane and I know Bill knows it. I’ve been giving the real data away why I am dead right. What is common to plants and animals that both lose in injury? Plants and animals lose the same thing when they get injured……..Becker 101. The DC current is what both lose. In plants when they lose it, they can heal injury by humans or herbivores. In humans, loss of the DC current often results in cancer. Why? Diana? Becker definitively shows that the DC current regenerates all cell lines plants and animals. Humans have lost the ability to generate the same current as other mammals. Why Diana? And how does Auxin tie to this mystery?

          • Jack Kruse

            How are like plants? If your ancestry is equatorial…….water is most critical to photosynthesis…….if your above the tropics……DHA is more critical to the generation of the DC current. Why? people with Tropical Ancestry more fragile to the effects of nn-EMF. Is that right?If you’re in between you need a mix of both……..
            if youre vitamin D 3 sulfate is low in your skin………in any place you live it tells you you are extremely disconnected from two things that plants are very connected too……….and your environment, as a mammal is the real issue in regenerative capacity………..
            For a complex organism it would be optimal if both were high……..would n’t it? So what happens in a microwaved human world Diana, with respect to light and ubiquitin?
            What does this mean for those in the tropics………..and those in poles?

          • Diana

            This study shows apoptotic effects directly:

            UVB-activated indole-3-acetic acid induces apoptosis of PC-3 prostate cancer cells.


            “Indole-3-acetic acid (IAA) has recently shown anticancer activity in
            combination with horseradish peroxidase. The current study demonstrated
            that IAA irradiated with ultraviolet B (IAA(UVB)) is able to generate
            free radicals and induce cell death in a time-dependent fashion in PC-3
            prostate cancer cells, while PC-3 cells treated with IAA alone exhibited
            no toxic responses. It was also found through Western blot analysis
            that the cytotoxic effect of IAA(UVB) resulted from apoptosis. Treatment
            with IAA(UVB) for 24 hours showed a significant increase in
            phosphorylated p38 mitogen-activated protein kinase and c-Jun N-terminal
            kinase, the stress signaling proteins. Furthermore, pro-caspases (-3,
            -8, and -9) were clearly down-regulated and poly(ADP-ribose) polymerase
            cleavages were demonstrated in the group treated with IAA(UVB). Flow
            cytometric analysis also demonstrated the induction of apoptosis by
            IAA(UVB) in PC-3 cells. In conclusion, this study demonstrated that IAA
            induced cell death in combination with UVB irradiation by increasing
            apoptosis in PC-3 cells.”

          • Diana

            LOL, Jack, so many words. Are you talking prevention, cause or cure? Let’s be a bit more clear.

            First, the current – do you mean depolarized cell growth? OK, but still it does not explain the malignant cancer with a malignant purpose (= cause). So is DC rather a co-factor? It could help in treatment, sure.

            Second, UV activated auxin against cancer cells (cell cycle arrest, to be precise): I think it rather shows common processes in animals and plants, in fact a lot to be learnt from plants regarding cancer – meaning prevention, cause and treatment!

          • Jack Kruse

            all of the above. Light controls nitrogen cycles and both together control carbon cycling in plants and animals. Plants are alway connected to the Earth magnetic field and canopy unless modern man’s inventions disconnect them, hence they get fewer diseases than animals like humans do. We make it a habit of inventing things to disconnect us from nature.

          • Bruno

            So, Diana – are you saying we are plant-like or that we have plant-like symbionts? I thought our microbiome is prokaryotic?

          • Diana

            Bruno, both animals and plants are eukaryota and share both prokaryotic and eukaryotic symbionts.

          • Dan Ordoins


          • “Compare that to eating. Maybe we spend an hour total eating meals…. It effects us
            only when we eat.”

            I would only add the role of meal timing (not “diet” per se) in setting the food-entrainable oscillator, or the circadian clocks present in virtually every peripheral tissue…

          • A central role for ubiquitination within a circadian clock protein modification code.


          • This Old Housewife

            Like that would work with hormone-driven cancers…

          • Amie

            Isn’t this a discussion of opinion, not a shaming?

      • Diana


        Care to explain, Dr. Lagakos?

    • This Old Housewife

      My family too–join the crowd.

  • Joshua

    Clearly LC for fat loss and “maybe” Keto for brain growth and health, rather than fat loss. Ketones may be an even more efficient fuel than glucose, providing more energy per unit oxygen And keto increases the number of mitochondria Toss in a ton of DHA and you’re living smart. The question would be “how much keto” is the needed for those benefits.

    TL;DR. LC for weight loss, VLC for brain growth. (Lots of DHA in both cases).

    • I know you know this, but I prefer “seafood” over “DHA,” because:
      1) “DHA” could be interpreted as supps (which are better than nothing, but not better than seafood); and
      2) seafood is good for more than just DHA.

      but yeah, agreed about other potential benefits of ketosis 🙂

  • CynicalEng

    Gardner came to the opposite conclusion in Sears vs Atkins with Sears’ ZONE diet being notably useless.

    How do we rationalize the two studies ? I can see where the Sears as author problem comes up….

    • 1) I’m well aware of Gardner’s work! Sears’ study was MUCH better controlled. Gardner basically just gave them diet books and sent them home, whereas Sears provided all of the food for 6 weeks.

      2) “I can see where the Sears as author problem comes up” … did you find any flaws in the study?

      • CynicalEng

        Gardner used only women, reducing variability and hence increasing power, and had a much longer timescale. If their free living book reading Atkins subjects lost 6 kg in 6 *months* but Sears achieved 6 kgs in 6 *weeks* with what at face value was the same calorie intake then it’s going to take a better man than me to explain it.

        Gardner is perhaps a better test of what happens in the real world outside of metabolic wards or jails.

        As a cynic the vested interest factor with Sears and his employees is a bit blinding for me – “SLT, the research chef, received consulting fees from the Inflammation Research Foundation. HH is an employee of Zone Labs Inc. BS is a stockholder and serves on the boards of directors of Zone Labs Inc and Zone Cuisine Inc and is also on the boards of directors of Zone Café and ZoneNet. None of the other authors had any personal or financial conflict of interest.” Sears set up the Inflammation Research Foundation.

        • “Gardner is perhaps a better test of what happens in the real world outside of metabolic wards or jails.”

          Perhaps. In Sears’ study: “Food intake was well-controlled. This is an important point.”

          • CynicalEng

            Possibly interesting citation statistics :-

            Web of Science
            Gardner – 390
            Johnston (Sears) – 42

            Gardner – >100
            Johnston – 13

            Secondary peer review in action ?

      • CynicalEng

        I did uncover a potential problem with calorie restriction – the diets were set at 1500 calories for everyone, while there was a difference in the REE of the groups hence a difference in “deficit”. Unfortunately the reported units appear incorrect as they lack a time dimension – kcal/kg ??

        • There was no significant difference in REE between the groups at any time point.

          There was a change from baseline, but it was similar in both groups.

          • CynicalEng

            Well the energy units are wrong, so anything could be happening. But the small sample does make statistical significance a challenge for sure –

            ????KLC diet group5.80 ± 0.30NLC diet group6.64 ± 0.46

            6.64/5.80 = 1.145 which might be 2000 vs 2290 TDEE, feed them a 1500 diet and the deficit is 500 vs 790 ie the latter is 58% greater.

            So individual deficits and loss data are required to fully understand this. Plus correct units 🙂

          • For this post, I played by the “statistical” rules and mentioned no significant difference in fat loss between the groups, but…

          • CynicalEng

            yep, I noted that. Fat mass per kcal deficit would be interesting, if somewhat elusive. I find I can’t rationally explain the difference in outcome between Sears and Gardner, which ought to be possible other than simply blaming under or inaccurate reporting.

            What happened at week 4 is another interesting question, as the lines start to diverge then.

            Nobody has resolved the units problem ?

  • Charles Richardson

    Interesting take as always Bill. Of course you’re confusing those who want simple answers with all this science-y stuff, but that probably can’t be avoided. And of course that is the problem. It ain’t simple. I don’t think there’s one “obesity,” there are multiple routes to it, and a few routes out of it, depending on so many factors. So depending on the cohort, we go back-and-forth or sideways. I didn’t know that Peter A. had stopped with the ketosis approach, interesting. I did it off-and-on for 40 years, but it finally stopped working for weight loss or general well-being. I still have to stay low carb, but not so low as to go into ketosis, and I would guess, for many, that’s going to be the long-term strategy by necessity. (Also I think VLC does play havoc with the gut microbiota, but that’s a different discussion.)

      • Charles Richardson

        These are short term studies, right? I’m talking about long term, like a decade or more.

        • sure — the ‘biome responds fairly rapidly to dietary changes.

          did you see something which suggests long-term detrimental effects?

          • Charles Richardson

            Admittedly purely anecdotal. Having been mostly LCHF since the 60s, I found that improving my microbiome (with prebiotics like RS and probiotics) made significantly positive improvements in health (digestion, energy, mood). I’ve heard the same from other long-term LCers. It seems to make LC fundamentalists angry when that’s mentioned, either by me or others, but anecdotal evidence is still evidence, just not proof. And I imagine it’s highly individual. The Perfect Health Diet people say that starches are important because of “glucose deficiency,” but I think it’s probably gut microbiome starvation. IMO. YMMV. etc.

  • Tuck

    Bill, do you think the severe calorie restriction on its own may have confounded the results? We’ve seen other studies where the body doesn’t react well to calorie restriction in excess of what the body self-adjusts to when carbs are restricted.

    That could explain the lean mass decline…

    • ?
      body comp improved in both groups, and change in lean mass over time wasn’t statistically significant

  • “The calculus of calories: quantitative obesity research”

    ^^^ video by the inimitable Kevin Hall

    • CynicalEng

      I have experience of mathematical modelling, I’m not convinced we know half of the equations to pull this off with obesity. Kevin’s recent 6 day -800 cal carb vs fat restriction study for example – would that be predicted ? 10 vs 20 vs 30 % protein ?

  • “Energy balance must be considered when deciding whether a certain amount of carb is “low.” Context always matters.”

    AMEN. a 50% carb diet is a ketogenic diet if energy is restricted to 1000 calories.

    Calories simply matter a hell of a lot and this is true even if you are on keto. My blood keto is way way better if calorie restricted keto relative to ad lib keto. Even if the calorie increase is 100% dietary fat, ketones in blood are suppressed in proportion to higher insulin reactions induced by greater dietary fats. Dietary fats do induce some insulin, via greater IR (a normal effect of blood lipid/FFA) and glycerol. The result is greater insulin and inhibition of native FFA release and ketogenesis even …which absolutely WILL happen if you are plowing butter to keto nirvana. If you’re a metabolic fail lardass you’re far more likely to induce hyperinsulinemia and ironically lower ketones. BT,DT.

    “In my opinion, one of the biggest strengths of carb restriction for weight loss is the spontaneously reduction in food intake seen in obese insulin resistant patients. ”

    Huge part of it, yep I agree.

    My take:
    Ketosis is wonderful. I think for the super obese with significant metabolic problems, nothing compares. Its better than low carb. I’ve recently experimented with raising protein. The result? Glucose-like massive hunger , worsening GI problems (likely related partly to greater glucose), total suppression of ketones which is at least partially related to the massive hyperphagia I developed.

    OTOH, for people with moderate to no weight problem, the general consensus is nothing inhibits the appetite like protein. They have no insight into what it is like to become hyperphagic from protein, which seems to be a liability only the major metabolically FUBAR have to live with (e.g. woo, jimmy moore). Protein literally makes me hungrier if I eat in excess; I”m not describing “lack of satisfaction” but a carbohydrate-like reactive hypoglycemic cycle develops. I kid you not. it is more difficult to moderate tons of chicken breast than highly seasoned/flavored ketogenic deserts for this reason. It also totally fucks up my brain from energy disorder.

    Then on the other hand, you’ll meet moderately overweight people who can’t even IMAGINE over eating meat and protein, the idea disgusts them and they have zero insight into shakiness/weakness/starving hunger from chicken breast and drumsticks. “The only time they felt that was that one time they drank a lot of soda while not sleeping”, and meat is simply nauseating to them.

    I’ve also noticed there is a subpopulation of very overweight people who have serotonin deficits – they have OCD or anxiety/panic, a history of binge eating disorder, and they do horribly with low protein. Protein is not given enough credit for being serotonergic, and IMO a large benefit of the protein diet for weight loss/control is through its high serotonergic activity. OTOH, I find the protein induces almost a fall-depression like quality from melatonin/serotonin excess, like overdoing 5htp.

    But for anxiety/panic/ocd patients with binge eating? Only protein will help them. It’s extremely serotonergic. There is a myth carbs are serotonergic, false, protein is extremely serotonin generating. That can be good or bad depending on the patient.

    Take home point, the idea that “lower is always better” or “keto is always best” is simply not true. Different interventions for different problems.
    I dont have anxiety/OCD Or binging, and serotonergic interventions sedate/depress me… like protein.

    It also doesn’t inhibit my appetite for a shit, because i make too much glucose from it // my metabolism is too awful. OTOH, keto is perfection in every way – mental, metabolic, nothing comes close.

    People need to experiment, observe, and absolutely should not be discouraged from doing so by zealots.

    • rs711

      i second that

    • Sky King

      Personally, I thrive on protein. And it’s why I consume at least 150gms/day of high quality protein from various sources such as high-quality whey, eggs, tuna, full-fat Greek yoghurt, and mainly pasture-raised meat. I drink a gal/week of organic State certified raw milk that comes straight from a farm and use it to make my whey “smoothies”.

      As for fats, I cook with coco oil, ghee and Kerry butter, and I’ll have 2 Tbs of Red Palm oil with my vitamins every morning. I’ll use olive oil on my salads and make my own mayo using avocado oil along with some olive oil.

      I restrict my carbs to mostly green veggies, along with organic berries (strawberries, raspberries, blueberries, etc.) which I mostly eat with my Greek yoghurt.

      I don’t worry too much about getting ketones because I think I get enough of those when I’m fasting, which I do for the 1st 4-5 days every month and every Monday of the week. Every few years, if the mood strikes me, I’ll fast for the whole month of January! And when I am eating, I’ll also eat a small piece of protein by itself at supper time and then nothing until the next morning. I don’t test for ketones, but I’ll just assume I’m make plenty during those times.

      I should mention that I work out w/weights 3x/wk, and have been doing so for some 30yrs having competed in amateur bodybuilding competitions during my 20s. I also do sprints on a ex. bike 2x/week. Working out with weights was probably the luckiest thing I’ve ever done/started in my life since it turned me on to nutrition, esp. learning the power of protein and the restriction of carbs in one’s diet. Having a degree in Nat. Sc. also helped in understanding the biochemistry of it all. But, I’m no doctor. Nutrition in general has been a hobby of mine for a long time (since I started working out in my teens) and it’s the reason why I peruse sites like those hosted by Bill and others.

      I think all of this has helped me to maintain a body fat level of between 7-12% all these years with no health problems whatsoever to speak of. And THAT works for me (n=1).

      If all of this sounds too spartan and boring, perhaps it is. But I never really enjoyed eating, per se. I guess you could say that I eat to live, and not live to eat.

      Cuique suum!

    • ^^^ epic

      interesting points about the OCD/protein/serotonin connections.

  • donny

    At 2000 calories, thirty percent carbohydrate, I’d be hungry. With more ketogenic ratios, I’m not. I tried the Zone years ago, it worked for weight loss, at the very restrictive calorie levels that Barry Sears advocates in his books–but it failed in maintenance, at maintenance levels, I was just too hungry.

    I think this is a problem with calorie restriction. Restrict calories, postprandial and fasting insulin will go down. Get to maintenance–unless you go into maintenance as sort of a plateau, where no post-diet increase in calories is necessary, insulin is going to be higher in maintenance. Is there any guarantee that this won’t make you hungrier in maintenance, at a higher calorie intake, than you were during weight-loss, at a lower calorie intake? At that point, moving macro’s around might lower insulin, which might make maintenance easier.

    • Van Dieu

      I concur. Everyone says that you end up lowering your total caloric intake on keto because it supresses hunger, but that is not my experience.

      I follow what I consider a well-formulated LCHF (10% carb) plan and eat to fullness. I tracked my caloric total for a week and it was in the region of 4,000-4,200 kcal/day. I weight 148lbs, and my weight is as stable as a rock. I do exercise more than most people, about 1-2hrs/day. For me that felt the amount of food I needed in order to fuel myself properly and not leave myself hungry. There is no way I could survive on 2000kcal and not be miserable.

  • Thomas Hemming Larsen

    This is truly a great post. This is such an objective message and it comes across very clearly (again, you’ve improved on the linguistics).
    I think part of why ketosis has received so much attention is because it has a name and is the polar opposite of norm. I know I’ve said it before but after reading your posts about all of this, I’ve become more comfortable eating more protein and carbs (still more low carb than most). Now I really feel that I can perform in the gym and the six pack is looking better and better 😛

    • malcolm

      I’ve been adapting to ketosis for a year now and I can perform in the gym, on the road and in the hills as well as I ever did on carbs. I’m not interested in six-packs.

      • Thomas Hemming Larsen

        Maybe I should have clarified that my performance in the gym has not changed from eating more carbs but from eating more protein and salt. I wasn’t talking about carb loading or anything like that. I don’t think carbs are ‘necessary’ for performance but they are not the enemy of everything either.

      • I’m very convinced this is possible, even at high levels of intensity.

        • Dan Ordoins

          This has been my experence after now years of adaption.
          One thing I have been including more of lately is salt, specifically quality sea salt (Aztec sea salt) and has made a huge difference in energy, performance and sleep. I have 2-3 or more teaspoons a day. Something I got from Ben Greenfield.

          • speculatively, a lot of people report better energy levels with by increasing salt intake… could be related to salt-wasting due to low insulin

  • This Old Housewife

    Even the Atkins website says that the keto phase is only to be practiced for a couple of weeks. I myself have been continuing keto, because i cannot handle the extra carbs without repeat weight gain. A single ounce of Wensleydale cheese stalled me, so forget about adding back any veggies or anything beyond Induction phase. Fructose halts my efforts, so no fruit. I’ve even had to curb protein intake to get any weight loss going.

    Hubby, OTOH, got his metabolic wheels greased (ha-ha), and he’s been steadily losing for the past year. As long as he doesn’t stray far from Induction, he’s okay.

    Last month, he got heart palpitations, so away we went to his primary doc (nothing wrong), then a cardio specialist (again, nothing wrong), and then a VA doc (they’re always clueless). I fixed him myself after paying a visit to Dr. Search Engine–found chat room discussions about this very thing back in 2008, and one lady got hers to go away by mixing a beta blocker with baby aspirin for a week. It worked for both her and Hubby.

    • rs711

      Was he given the beta-blocker Atenolol?

      I got my father off Atenolol ~1yr ago after having explored a bit of the research behind it. It was quite surprising to notice how big a difference it made to his stress response and nervous system: exercising at a high intensity was quite difficult & scary because of the adrenergic downregulation (which is the mechanism via which heart ANS activity is modulated): after a few months of progressive HIIT & getting off it slowly, his response to exercise is better.

      Except for acute instances like post-infarction HR control (for e.g.), long-term it’s quite ineffective with substantial downsides.

      However, the mix with baby aspirin is interesting and makes sense (off the top of my head).

  • Kindke

    fats induce very high GIP secretion from GI tract and GIP has insulin mimetic properties when acting on adipocytes.

    also reduced appetite is usually induced simultaneously with ( and probably by ) sympathetic drive so its not so obvious if people on low carb are losing weight because they are eating less or because cAMP in adipocytes is working better due to sympathetic drive.

    • the “Taubes 101” reply:

      “or they’re eating less *because* cAMP in adipocytes is working better due to sympathetic drive”

      probably too simplistic, but plausible nonetheless

  • rs711

    lol i love how you have to state you’re not “anti-keto” ==> a sign of muddy ‘progress’ (?) because now camps are getting established (sigh).

    33% & 31% protein are high-protein diets, whether or not the rest is made of fat or carbs. it’s very close to ‘rabbit starvation’ percentages (35-40%). However (keeping in mind the point made by woo), the fact that it’s sufficiently low kcal (1,500) will still make the diet quite (body) fat dependent.

    It’s a bit of a tortuous way of testing fat-reliant diets, don’t you think? Not useless by any stretch of the imagination, but a bit inelegant.

    the weight loss results don’t surprise me to be honest. if they are to some, my guess is it’s because ‘metabolic efficiency’ is conflated with long-term ‘caloric balance’. ketosis differentially affects mitochondria compared to LCHF or HCLF but this does not entail our system-of-systems (i.e. body) will reflect that in a 1:1 manner. their needs to be some degree of independence otherwise life-saving, quick adaptations couldn’t occur [it’s analogous to how slow, giant companies use smaller branches to roll out new riskier products quicker and with less on the line if things go awry].

    as you say ==> “…watching “calories in” matters less… calories still matter, but the need to monitor them doesn’t…”

    • ~120g is not high protein, especially for obese adults!

      • rs711

        agreed, but for a ~1,500kcal diet.

        Double that and you get 240g of protein, close to a livers’ upper metabolism limit ?240g isn’t harmful per se at all, but it’s fair to consider such a diet high in protein for average humans.

        i was unclear, i didn’t say I was extrapolating to ad lib diets 🙂

  • RIchard Feinman

    The objection to the study is not that the authors have a skin in the game but rather that you can tell that they have a skin in the game.

  • Van Dieu

    Bill, the one “flaw” I can find:

    From reading the full text, and the table2 breakdown ( it looks like the test subjects were dominated by women – each group 2 men, 8 women.

    I do believe that keto diets are more complicated for women because they are (to put it a little bluntly) more complicate hormonally. I am sure that the study would produce a different conclusion had the subjects been more evenly selected from the sexes or and much different had they been male dominant.

    Maybe Sears knew this?

    • if there were significantly more women in only one of the groups, then yeah, I’d agree that’s a problem.

      • Van Dieu

        I was more skeptical that the test subjects are not representative of the general (overweight) population in either test group or control. Would you still be ok with the testing protocol if they tested on only women? Would you be happy if statin trials were only ever performed on men? Surely the test/control populations should be broadly representative of the real world usage..?

    • CynicalEng

      It should be a rule that small studies stick to one gender – mixing them adds a whole load of variability in height, weight, FFM, etc that serves to make significance more difficult to achieve.

  • RIchard Feinman

    The title of the study is “low-carbohydrate diets,” not a low-carbohydrate diet. In other words, this is it. This is definitive and if anybody found anything different, this supersedes it. In other words, it’s all settled. I don’t remember much about the paper but I am guessing that the error bars are SEM, that is, more variation than you can tell graphically. In any case, 2 kg is not a huge difference (I lose 1 kg overnight). I personally have no skin in the game but it is that this is politically charged — there is no sense that we are trying to find out something.

    • rs711

      I’ve talk to Barry Sears on Facebook about his claims that ketogenic diets are inherently unhealthy hormone-wise (for both men & women). Needless to say, it was underwhelming. The second we get into:

      – mechanistic plausibility
      – undue assumptions (e.g. all changes from norms MUST be pathological)
      – evolutionary implications
      – assuming this is true, what would that mean for the reams of other positively changed markers etc.

      These aren’t points that only a top-notch scientist can raise…these really are the bare-bones considerations any self-respecting *scientist* should recognize as relevant, at the very least.

    • “2 kg is not a huge difference”

      Agreed. Low carb works, and lower isn’t necessarily better (in this context).
      This study *didn’t* say that ketogenic diets don’t work (and I agree; keto can work quite well for many people)

      • RIchard Feinman

        Bill, you and I are in agreement except perhaps on whether Johnston, et al. is a good paper. One of the things that is a serious defect (which it shares with most of the papers in the literature) is the group statistics. Nobody loses an average amount of weight. What you want to know to decide if you will try any particular diet are the odds, that is, how many people in each group did better than how many in the other group. We offered a reasonable way to do this in We didn’t realize at the time but it is a variation of the Wilcoxon test and brings out the differences and tells you whether you want to try one or the other diet.

        • wrt “group statistics”

          I see a value for subgroup analyses in this context. It’s been a while but I still hold Gardner’s work in high regard… can’t help but wonder what other biometrics could predict someone’s potential response to a particular intervention. Who knows, maybe a simple blood test will be able to tell us if a patient would do better on, eg, low carb with high fat or high protein, or even low fat! (as Gardner showed is the case for insulin sensitive obese patients).

          • RIchard Feinman

            Gardner’s study would benefit from knowing individual responses but the real problem is that “diet” is not a biologic variable. The one of interest is carbohydrate and, also, weight loss may not be the best indicator of physiologic state. I plotted carbohydrate at each of Gardner’s time points for each diet against triglycerides. Results are at
            and you can see that carbohydrate is the controlling variable.

  • Diana


    you said “Isn’t this a discussion of opinion, not a shaming?”

    Regarding “ketones starving cancer”: I have presented some facts, the others opinions, beliefs and… words. Take your pick.

  • Matias M

    Still using humans with obesity and overweight who are already pathological. Will be great to se “normal” metabolisms,and by this i meant active guys submitting to diets studies….We need to see how this normal metabolism respond to different diets….

    • interesting… for what end point, specifically?

  • TechnoTriticale

    Hyperlipid is also about Gardner this week:

    He concludes: “People must make up their own minds.”

    With any supposed LC trial diet, I immediately wonder about what carbs, what fats, what prebiotic fiber, gut biome status, thyroid status, supplements, subject genotypes, and of course detailed food logs. There are likely other major factors as yet not routinely factored into nutrition trials. It will be interesting to see how comprehensive the controls are for the NUSI work in progress.

    So in the meantime, we each have to place our own bets and watch for results with as little confirmation bias as we can muster. At my house we’re awaiting 23andme raw data, to have some other sites chew on, for possible further nutritional optimization.

    • haha saw that. I think it was a “reply” to this post 🙂

  • Jack Kruse

    And this is for Diana………… I think you might like this Bill. I believe this is the confounder to your new gluten blog too……….the paleo blind spot. Blue light exposure also causes a leaky gut by lowering the enterocytes DC charge.

    • Diana

      “And this is for Diana”

      — thanks Jack, interessant

      What is your opinion on non thermal plasma, concerning cancer treatment?

  • Ella

    Fabulous article. THANK YOU SO MUCH! Now I know why the Life Without Bread program (from the book of the same title), worked so well for me. I feel awful on very low carb diets. Thank you so, so much for this wonderful article.

  • Pingback: Carbs: Low vs. Lower | LMGTFY()

  • Ketogenic dieters lost more fat mass, but much more fat-free mass than moderate-carb dieters in this study: :/

  • Jethro Bodine

    Dr. Lagakos you said “Energy balance must be considered when deciding whether a certain amount of carb is “low.” Context always matters.”

    Could you please provide guidelines to calculate if a diet is low carb based on overall calorie intake.

    • I can’t give you an absolute formula, but, for example,

      “42% carbs in a pretty big energy deficit is modestly ketogenic (~0.2 mM), and still conducive to the loss of body fat without causing hunger. Some might argue that 157 grams of carbs isn’t Low Carb™.”

      If they were gaining weight on a diet with 3000 kcals (ie, energy surplus), I wouldn’t consider 42% carbs to be “low,” because it would be >300 grams and not be ketogenic.

      A blood ketone reading of ~0.2 mM is a pretty good indicator that your diet is low carb.

      • Jethro Bodine

        Thank you doctor, that’s great news!.

        Is the ketonix a good tool to obtain blood ketone readings?

        • You’re welcome!

          Ketonix measures breath ketones (acetone), but should correlate fairly well with blood ketones (beta-hydroxybutyrate) and even urinary ketones (acetoacetate) for that matter 🙂

          That said, blood ketones is the ‘gold standard’ (and unfortunately, the most expensive).

  • Eve

    Why did Attia revert to low carb? I recall the post where he discussed pigging out on cake, but don’t recall anything about what specifically motivated his decision.

    • iirc, he didn’t bash keto, just said it wasn’t for him

      • Eve

        Thanks, glad I didn’t overlook something critical. Just out of curiosity, for people who work late evenings and get home around midnight, what do you think is optimal as far as eating times are concerned? I’m trying to switch my natural eating rhythm to a big breakfast and light dinner, but still find myself ravenous and craving carbs late at night when I get home. Adding to the challenge is that my workouts need to be before work, and large meals before exercise make me perform poorly.