Thursday, January 12

Safe starches, blood glucose and insulin

A reader asked me recently about a subject which is confusing many people in the paleosphere. 
"Jaminet in his debate with Rosedale suggests higher carb diets tend to lower blood sugar whereas low carb diets, RAISE it. Can you help me untangle what is going on here? It makes it sound like the more carbs you eat the better your blood sugar levels which does not seem right to me. Clearly, an important health goal is achieving low blood glucose so I would want to know what is the best way to eat to control them. 
I always assumed that the less sugar you eat, the less blood sugar you'll have. Is there a threshold? If Jaminet is correct, then shouldn't we see a higher fasting glucose associated with ketogenic diets that are totally carb restricted vs higher carb diets? I know excess protein might be converted into glucose but if you followed a ketogenic diet with low protein would you still see the rise in blood glucose? 
What is the mechanism through which blood glucose is being lowered in high carbers? Do they secrete more insulin to deal with it hence lower blood glucose? Would their insulin levels therefore be higher even if blood glucose was relatively low? Which is worse for health- low glucose/high insulin or moderate glucose/low insulin? 
What is the mechanism through which some cancers are being suppressed with ketogenic diets if not through lowered blood glucose? Is there something else going on?"
These are very important questions as they raise some concern in people which utilize a low carbohydrate diet for controlling their blood glucose (BG). Before trying to elaborate an answer, there are some facts that must be kept in mind:

  • Hyperglycemia is not a disease, it is a symptom. 
  • BG levels can be affected by non-dietary factors.
  • The two principal energy substrates for humans (glucose and free fatty acids (FFA)) compete with each other for their utilization.
  • Calories matter.
  • There are differences between physiological insulin resistance (PIR) and pathological insulin resistance (PaIR). The term "insulin resistance" is very vague, it doesn't define explicitly which tissue(s) is IR.

The first issue to adress is whether ketogenic diets raise BG levels. The only evidence I have seen for this happening is in anecdotes from people in the internet. But if we want to have an objective look at the subect, we must see what happens in studies done with ketogenic diets (I will use low carbohydrate and ketogenic diets equally). 

Ketogenic diets and blood glucose levels

Most studies done on ketogenic diets are short-term and involve weight loss. All of them show a reduction in BG and insulin levels. A study by Grieb et al. (1) found that people eating an optimal diet (Kwasniewski) had on average a BG level of 87.9mg/dL, which is in the normal range; and very low values of HOMA-IR. Sharman et al. (2) have shown that the metabolic benefits of carbohydrate restriction are independent of weight loss. Given the evidence, it is only possible to speculate about the mechanisms by which BG levels rise in some people eating a ketogenic diet.

The goal of a ketogenic diet is to simulate fasting, but without the negative effects of prolonged nutrient restriction. Before going on, it is pertinent to remember the Randle Cycle (3):

In short, both FFA and glucose compete with each other for their uptake and oxidation. This can be translated as when BG is high, FFA utilization is low; and when BG is low, FFA utilization is high. Ketogenic diets are characterized by low BG levels, in part because of a drastic reduction in exongeous glucose. In turn, plasma FFA rise from dietary and endogenous sources (the contribution of each one depends on energy balance). During this scenario, plasma ketone bodies also rise. So we have the following metabolic milieu:

Cellular effects of a fasting-type metabolism

For exerting it metabolic effects, insulin needs to first bind its receptor (the insulin receptor, IR). Upon binding, insulin triggers an intracellular signaling cascade, which influences both the function of intracellular proteins and gene expression. The signaling pathway triggered by the binding of insulin include the recruitment of the IRS (insulin receptor substrate) to the cytosolic part of the insulin receptor dimer. The signaling cascade stimulated by insulin is essential for its function. If proteins involved in this signaling pathway are inhibited, there will be no cellular response to the binding of insulin and the activation of IR.

One level of inhibition of glucose utilization by FFA involves the inhibition of GLUT4 translocation to the plasma membrane. The translocation of GLUT4 is stimulated by insulin, by activation of IRS, PI3K and other proteins (4, 5). In vitro studies have shown that palmitate, the main fatty acid stored in mammalian adipose tissue, inhibits GLUT4 translocation and activity (6, 7). This results in reduced glucose uptake in skeletal muscle.

Inactivation of PDH (pyruvate dehydrogenase) is one of the most important mechanisms for inhibition of glucose oxidation  by FFA. PDH activity is controlled by phosphorylation, by PDK (pyruvate dehydrogenase kinase) and PDP (pyruvate dehydrogenase phosphatase). Phosphorylation by PDK inactivates PDH, while dephosphorylation by PDP activates it. Fatty acid oxidation increases the mitochondrial ratios of [acetyl-CoA]/[CoA] and [NADH]/[NAD+], which inhibit PDH. Low carbohydrate diets have shown to reduce muscle PDH and increase PDK (8, 9), effects which are reversed by a carbohydrate refeeding (10). Fatty acids also increase the concentration of cytosolic citrate, which inhibits 6-phosphofructo-1-kinase, providing another mechanism of inhibition of glucose oxidation (3). Fatty acids can reduce phosphorylation of IRS-1 (11), GSK-3b and PKB/Akt (12), thereby acting also downstream of IR and IRS.

The metabolic response to fasting can show what are the effects on insulin signaling of very high levels of plasma FFA and ketone bodies, but within a physiological range. In a very interesting study, Soeters et al (13) found that insulin-mediated peripheral glucose uptake after 62h of fasting was significantly lower compared to 14h of fasting. They also found that after 62h of fasting, Akt phosphorylation at Ser473 and AS160 phosphorylation at Thr642 were reduced. This implies that insulin signaling was attenuated (reduced phosphorylation of Akt) as well as glucose uptake (phosphorylation of AS160 is involved in the translocation of GLUT4). The authors concluded:
"(...) it is possible that pAKT-ser473 is involved in the physiological adaptation to fasting, inducing a reduction in peripheral glucose uptake and protecting the body from hypoglycemia."
Intramyocellular triglyceride accumulation is thought to mediate fatty acid insulin resistance. This is one way by which some authors think that a high-fat diet leads to insulin resistance. Compared to fasting (67h) a very low carbohydrate diet (eucaloric) produces the same amount of IMTG accumulation, both produce glucose intolerance and reductions in insulin sensitivity (14). Thus, the factor for triggering this metabolic response seems to be the absence (or drastic reduction) in glucose availability (my bolds):
"Thus, we suggest that dietary-induced IMTG accumulation and insulin resistance in healthy humans may be largely influenced by circulating FFAs, whose availability (in turn) is regulated by dietary CHO intake. (...) our study provides support for the hypothesis that the physiological trigger for this coupling in the healthy individual may be a short-term challenge to dietary CHO availability. That we have observed these diabetogenic alterations in a physically fit population, which is purported to be insulin sensitive yet exhibits high IMTG concentrations (the ‘athlete paradox’) (Goodpaster et al. 2001), supports our contention that they represent an adaptive rather than pathological response. This substantiates our previous assertion that alterations in glucose tolerance and insulin sensitivity associated with dynamic changes to the plasma and/or lean tissue lipid profile are part of a normal co-ordinated adaptation to short-term changes in food availability (Stannard & Johnson, 2004) and perhaps, more specifically, to fluctuations of dietary CHO availability. (...) This short-term alteration is teleologically sound because it limits competition between skeletal muscle and glucose obligate tissues for circulating glucose substrate when its availability becomes limited. Irrespective of a causal relationship, the coupling between IMTG accumulation and reduced insulin sensitivity may also represent a co-ordinated adaptive (non-pathological) response to CHO stress  (Johnson et al. 2003). A concomitant resistance in muscle to the effects of insulin on glucose uptake during CHO stress maintains normoglycaemia and thus the preservation of plasma glucose for use by the CNS and glucose-obligate tissues (Reaven, 1998). Dissociation of insulin action by way of muscle insulin resistance rather than attenuation of insulin secretion means that residual circulating insulin levels can be maintained (Klein et al. 1993), thereby preventing rampant proteolysis (Fryburg et al. 1990), lipolysis (Kather et al. 1985) and perhaps hepatic glucose release, whilst unnecessary uptake of blood glucose by muscle is prevented."
So, from the studies above, we can conclude that:

  • FFA supress glucose uptake and oxidation, resulting in muscular insulin resistance, without reducing insulin secretion.
  • These effects seem to be dependent on dietary carbohydrate restriction.
  • FFA-induced muscular insulin resistance is a physiological response to low availability of glucose. 
  • Under normal conditions, this serves to maintain adequate BG levels. When FFA are in excess, there might be a rise in BG levels, because oxidation and release of FFA are not coupled. This leads to insulin resistance in other tissues like the liver (15), consequently failing to control hepatic glucose output.

Blood glucose levels and high carbohydrate diets

Without any biochemical explanation, logic dictates that if we eat a high carbohydrate diet, glucose oxidation pathways are stimulated. This is the opposite of what we observe with carbohydrate restriction, that is, stimulation of insulin signaling. Glucose and insulin both regulate GLUT4 and GLUT1 in muscle cells (16) to increase glucose uptake. The Randle cycle dictates that glucose stimulates its own oxidation and reduces fatty acid utilization. As shown above, glucose reduces PDK and increases PDH. Insulin inhibits lipolysis, further facilitating glucose oxidation. In healthy subjects, a high carbohydrate-low fat diet can improve insulin sensitivity (17, 18). It makes sense, carbohydrates supress fat oxidation and increse glucose oxidation. Overall, there should not be a rise in BG levels on a 24h basis, if anything, we can expect a reduction, because we are utilizing glucose as our main substrate. 

The common ground: calorie restriction

Until now, we have seen that carbohydrates stimulate glucose utilization (insulin sensitivity) and that FFA supress it. How can then a ketogenic diet produce such good results in people with diabetes? Diabetes and MetSyn are characterized by lipotoxicity and glucotoxicity (19). This means that there is an abnormal level of plasma FFA and glucose, produced by PaIR. Insulin cant supress hepatic glucose output, muscle cells do not respond to insulin, and adipocytes liberate FFA in an uncontrolled fashion. In very simple terms, there is an excess of both energy substrates, each one inhibiting the utilization of the other. This scenario can be improved both by restricting fat (thereby increasing glucose utilization) or restricting carbohydrates (increasing fat utilization). In either case, calories must be restricted (directly or indirectly). So, people who show signs of glucose intolerance and switch to a ketogenic diet can improve their BG and insulin levels (by reducing glucotoxicity), but if energy is in excess, BG can start to rise. On the contrary, reducing dietary fat alleviates lipotoxicity, increasing insulin sensitivity. This is why any diet which is calorie restricted, independent of macronutrient composition, produces weight loss and improves glucoregulation. Calorie restriction, by producing a calorie deficit, alleviates both gluco- and lipotoxicity. 

One of the important aspects for dealing with this subject is the fact that glucose intolerance can have many underlying causes. In this manner, a person with autoimmune diabetes may not tolerate carbohydrates as well as a person with only mild PaIR. The fact that PaIR may progress into beta-cell dysfunction (20, 21) can alterate the response to a high carbohydrate diet, and depending on the severity, extreme measures must be taken to achieve normal BG and insulin levels (such as severe calorie restriction). The distribution of body fat can also have consequences on glucoregulation (22). Last but not least, epigenetic changes produced in utero can affect glucose tolerance since the moment we are born (23). 

What is more important, in my opinion, is to address whether hyperinsulinemia causes or potentiates IR, or if hyperinsulinemia results from IR, by a compensatory mechanism. If the first hypothesis holds true, then a ketogenic diet would have an advantage over a low fat-high carbohydrate diet. Desensitization of target cells triggered by the same hormone (homologous desensitization) is a very common characteristic of hormone signaling. In short, high levels of a given hormone reduce the response of the cell to the hormone effects and a reduction in the level of this hormone resets sensitivity. Excess hormone signaling is harmful, so the cell's attempt to restore normality is mediated by reducing its response. This is exactly what happens with insulin: 
  • Chronic hyperinsulinemia (in vivo and in vitro) causes a reduction in the number of receptors per cell and glucose transport (24, 25).
  • Pre-incubation of 3T3-L1 adipocytes with high levels of insulin and glucose increase PTEN activity, which is correlated with decreased PtdIns(3,4,5)P3 (26). This metabolite is very important for intracellular signaling transduction of insulin.
  • Hyperinsulinemia has shown to induce insulin resistance in humans (27).
  • Overall, hyperinsulinemia is proposed to be a result and a driver of insulin resistance (28).
Obesity seems to be characterized by an increased amount of insulin being secreted, compared to lean subjects (29). So, while calorie restriction per se is responsible for improved glucoregulation, there might be a short-term benefit in consuming a high-fat ketogenic diet in T2DM and MetSyn patients. As the bodyfat mass and associated hormones regulate, the differences between hypocaloric diets with different macronutrient profiles might be eliminated. This seems reasonable for diet-induced insulin resistance, but not for autoimmune or severe diet-induced glucose intolerance. There seems to be a threshold in which many people cant fully recover their insulin sensitivity with dietary measures. This is where a more integrative and previously uncharacterized approach kicks in (this is the subject of my future post). 

Glucose and cancer

Glucose restriction for cancer treatment seems reasonable given the evidence on the dependence of most types of cancer on glucose for cell growth and proliferation. Unfortunately, the picture is not that simple (30). Although restricting glucose is a good idea, specially for glucose-dependent tumors, the evidence shows that cancer cells also feed on glutamine. More surprinsingly, some types of cancer can grow on fatty acids (31). Restricting glucose reduces insulin levels, which promotes cancer growth. Nevertheless, ideal levels of blood glucose and insulin for treating cancer can only be achieved via calorie restriction. In fact, many supporters of ketogenic diets for cancer often cite the study of Zuccoli et al (32) on the management of glioblastoma. But very few mention what is stated in the study:
"Due to the hyperuricemia the patient was gradually shifted to a calorie restricted non-ketogenic diet, which also delivered a total of about 600 kcal/day. This diet maintained low blood glucose levels and slightly elevated (++) urine ketone levels due to the low calorie content of the diet."
Despite switching to a non-ketogenic (by definition) diet, the patient still showed progress. In my opinion, besides glucose and protein restriction, calorie restriction (and probably fasting) is the dominant factor for achieving success during cancer treatment. 

Summary and key points

  • Both energy substrates (glucose and fatty acids) support their own oxidation and inhibit the metabolism of the other.
  • A diet high in fat and low in carbohydrates will reduce glucose metabolism and increase fat metabolism. Conversely, a high carbohydrate-low fat diet increases glucose utilization and decreases fatty acid metabolism.
  • Increased glucose utilization implies upregulation of glucose membrane transporters and enzymes involved in glycolysis. Additionally, it reduces the activity of enzymes involved in fat metabolism. 
  • Increased fatty acid metabolism inhibits key glycolytic enzymes, as well as GLUT membrane translocation. It also interrupts glucose/insulin signaling and stimulates lipolytic enzymes. 
  • Chronic hyperinsulinemia, caused by peripheral insulin resistance and energy excess, aggraviates glucose intolerance. Both high glucose and high FFA levels promote this state, by different mechanisms. 
  • Under energy balance, a high fat ketogenic diet might produce muscular insulin resistance, reducing glucose tolerance. This should not be compensated by an increase in blood glucose levels. However, if energy intake exceeds calorie expenditure and/or the body utilizes predominantely FFA for energy for extendend periods of time, there can be a rise in blood glucose to non-pathological levels. This is specially relevant if there is little exercise being done (exercise promotes muscular insulin sensitivity) and/or there is an abnormal condition.
  • The etiology of glucose intolerance is very important for the proper treatment. Although calorie restriction is the primary solution for obesity/diet-induced insulin resistance, people with autoimmune (both congenital/perinatal or diet-induced)  and beta cell dysfunction should adopt a very low carb approach. 
In the end, the level of carbohydrates proposed by the Jaminet's is in the safe side. The alarmism promoted by some people is not supported. While severely restricting carbohydrates is, in my opinion, the best approach for MetSyn and obesity, once fat mass has reduced, one can tolerate more carbohydrate without problems. If the choice is restricting carbohydrates for life, you should expect a very abnormal response to any carbohydrate (being "safe" or "unsafe"). Nevertheless, lets not forget that the Perfect Health Diet is not a high carbohydrate diet, but a high-fat, low carbohydrate diet. Despite my obvious differences with Paul (33), his dietary advise is very reasonable and his diet is the first I recommend. This template, plus calorie restriction and/or fasting, is the best dietary measure one can implement. Everyone should adjust their individual carbohydrate needs, but in the end, the key is controlling and preventing inflammation. And carbohydrates per se are not inflammatory. 

*Certainly, there are people who are in the extremes of the Gaussian distribution. For these persons, extra measures should be taken. I will write about my approach in the following post. 


  1. TLS

    Excellent post! We've needed something like this. I like that you back up everything you say and always remain objective.

    I'm just going to ask a few questions here to make sure I understand, as the biology behind this is rather complex. Please let me know if I have it right.

    Let's start with assuming a 'normal' person, and how things would work there.

    (1) Eating more carbohydrates will up-regulate glucose utilization and suppress FFA utilization = improved insulin sensitivity.

    * This makes sense, but could this come at the expense of higher insulin secretion?

    * BUT, as I understand it, chronically high insulin levels over time could result in the cells becoming less sensitive to insulin.

    (2) Restricting carbohydrates and eating more fat will up-regulate FFA utilization and suppress glucose utilization. = decreased insulin sensitivity.

    * This *does not* necessarily lead to higher blood glucose unless there is an excess of calories.

    * BUT, it would imply more STABLE blood glucose levels, right? Less spikes?

    * It leads to lower more stable insulin levels.


  2. TLS

    More thoughts: I guess what can be summed up and agreed upon is that the OVER-consumption of energy is what is the MAIN cause of a lot of harm, be it carbohydrate or protein or even fats. Whatever plan you follow, eating less is the way to go.

    For example, carbohydrates aren't necessarily bad (for normal people) and can actually improve insulin sensitivity providing you aren't overloading your system with them because if you do that you will overly trigger insulin signalling and thus become less sensitive to insulin over time.

    And I suppose if you are restricting carbohydrates for life (ketogenic), it doesn't matter whether you are insulin insensitive or not because you aren't relying on glucose for an energy source anyway. And Ketosis is therapeutic for other reasons that go far beyond losing weight or controlling blood sugar.

    Ultimately, the biggest advantage to low carb approaches would then be in their ability to suppress appetite.

  3. I am a diagnosed type II diabetic. However, the disease is in remission right now, thanks to the Perfect Health Diet and losing a lot of weight. Your post rings true and probably explains why my fasting blood glucose levels go DOWN after eating safe starches. I blogged about this curious phenomenon at

  4. There is clearly a spectrum of tolerances, and where Wright Mind and many people I know can tolerate some higher levels of carbs, there are also people like me who must restrict to what most people consider extremely
    low levels-- <40g on average. I believe we see more of this carb sensitivity in women and older people. My concern is that anyone who promotes an all or nothing approach is treating diet and health like religious fundamentalists treat religion. Without carb restriction I would by now have been diabetic and severely obese; instead, I work to keep my weight in check which takes constant effort, regular BG monitoring, and serious attention to my calorie and carb intake.

    I am devoted to the scientific method, and am so glad to see Lucas applying it to this area of such great need.

  5. This seems to support the view of Ron Rosedale in his last post: blood glucose is not the whole story, and it should not be treated as some indicator of low-carb diet failure. It seems unarguable that CR is ideal, but I don't see any real reason to purposefully consume carbohydrates. The body's shift to conserving glucose for dependent processes (by upregulating FFA use where it can) in ketosis further weakens the already shaky 'glucose deficiency' speculation/hypothesis.

    In the healthy, carbohydrates are not poison, but they're not exactly required for continued health.

  6. Lucas, here is something different with "calorie-restricted ketogenic" and "calorie-restricted:"

    With my limited knowledge, it seems to me like the ketogenic diet's results are somewhat expected with a reduced-glucose diet, but the calorie restriction results look like a general "shutting down"? ...Why would receptor [those in the study] expression decrease along with decreased glucose utilization?

    Also, here is something interesting with regards to dietary glucose and glucose utilization, which I referenced on Masterjohn's new post:

  7. TLS,

    (1) Insulin secretion should be coupled to insulin sensitivity. If insulin sensitivity is high, there is less insulin needed for exerting its cellular effects. Chronically high levels might contribute to insulin resistance, but not because of carbohydrates, but because of inflammation and energy excess. An eucaloric or calorie restricted high carb-low fat diet does not induces chronic hyperinsulinemia because it promotes insulin sensitivity. Protein also modulates the glucose status (see (2)).

    (2) Correct. Being sedentary (even while maintaining an adequate body weight and being in calorie balance) might promote the increase in BG levels. If insulin sensitivity is adequate, there should be no significant "spikes". Dietary protein also influences glucoregulation:

    (Compare figure 1- blood glucose levels- and figure 3 -postprandial insulin levels).

    I might elaborate further on protein's impact on glucose tolerance in other post.

    Wright Mind,

    Happy to hear that! Most people with diabetes are not equal, and many patients fail to recover because conventional medicine seems to only look at BG levels.


    Thank you. I agree completely with you, that is why I wrote this post, for trying to explain potential mechanisms for anecdotes. You might be interested in my next post, which I think will help you in your journey (at least understanding some things that are probably happening to you).


    I agree with you, but you forget an important factor: sustainability. A more flexible long-term approach is more efficient for maintaing weight loss and overall health achieved initially with severe carbohydrate restriction. If you can live the rest of your life without eating another carbohydrate (like for instance, Rosedale), no problem. But I think that is important to drive carbohydrate intake by instinct, and if you are craving a "good" source of carbohydrate, go for it.


    At glance, I see one factor which influences any possible conclusion from the study: there is not KD-Ad libitum group. Ketonemia was only observed in KD-CR rats because CR-Std had 25% of protein (rats are very sensitive to protein for ketosis).

    To answer your question, although we are talking about receptors in specific brain areas, lets try to connect the dots. In the CR-KD, IGF1R mRNA levels increased along with IGFBP3 mRNA levels. IGFBP3 binds (he) IGF-1, diminishing its bioavailability. So, it is tempting to speculate that this reduction in availability of IGF-1 triggered an increase in IGF1R. There is also a nice discussion on the study about this.

    It seems to me that the reduction in GLUT3 expression follows a logic for increased ketone body metabolism (the body senses CR and shifts towards a ketolytic environment).

    The second study looks interesting but they dont mention calorie intake (at least in the abstract).

  8. TLS

    Thanks for the reply.

    In regards to (1) I understand that the more insulin sensitive the less insulin required to do the job but wouldn't there be a point where even in an insulin sensitive individual a very high glycemic load would still trigger higher insulin secretion as a result?

    One other thing I don't understand fully. Even in a guy who is insulin sensitive, wouldn't his BG and insulin fluctuate quite a lot during the day in response to his carb-rich meals? Wouldn't he have times during the day just after his meals where his BG and insulin rise high even if his fasting insulin/BG is normal?

    Further, would it be correct to assume that a low carb guy would largely avoid these sort of spikes and have overall better BG/insulin -stability- during a given day.


    1. Yes, but the effect of a fixed glycemic load depends on the individual. For example, a trained athlete with large amounts of glycogen would tolerate better a large glucose challenge than a sedentary obese person.

      BG/insulin fluctuations are determined by the sensitivity and tolerance, as in the example shown above. I dont think that a high carbohydrate diet is ideal, specially if eating large amounts of common carbohydrates consumed (wheat, refined grains, sugar). And remember that the level of BG attained after a bolus of carbohydrate is dependent on many factors, such as the presence of fiber, protein, fats, physical state of the food, among others. But, in short, yes, constant fluctuations might be a problem, but they depend on the factors mentioned.

    2. TLS

      Hi Lucas,

      I think I understand now!

      Basically, in ketosis, muscular IR is a temporary adaptive response-NOT a disease, that allows the body to conserve glucose for essential processes or for when it may need, hence you should have quite normal BG levels, but not necessarily high even if you avoid carbohydrates entirely.

      It also makes sense of why a person who eats carbohydrates can have a low fasting BG simply because their cells utilize glucose more and since their body depends more on external sources of glucose instead of self, by the time the test is done, under fasting, more glucose would have been sucked up by the tissues, hence low.

      This lends me to think that something like the HbA1C test would be a far better measure of overall glucose impact on the body.

    3. TLS

      Of course, this argument assumes a healthy person, in a person with some disease related IR, then it would be a completely different story. They would need to experiment with themselves in order to find their particular tolerance level for carbs.

      Fasting BG would reveal whether you are severely IR or not, but that doesn't give you the full picture.

      Am I sort of getting it right, now?

      Finally-am I right for thinking that resistance exercise could improve glucose utilization under ketosis?

    4. TLS

      Regarding what I said earlier, here is an article I found:

      `Hemoglobin A1c Outperforms Fasting Glucose for Risk Prediction`

      ScienceDaily (Mar. 3) — Measurements of hemoglobin A1c (HbA1c) more accurately identify persons at risk for clinical outcomes than the commonly used measurement of fasting glucose, according to a study by researchers at the Johns Hopkins Bloomberg School of Public Health. HbA1c levels accurately predict future diabetes, and they better predict stroke, heart disease and all-cause mortality as well.

  9. Nice article. I was checking out references about fasting glucose levels on ketogenic/low carb diets and they are lower in each study. However, those anecdotes are all from very long time low carbers (for instance Hyperlipid) and that is clearly different from all studies you referenced.

    And carbohydrates per se are not inflammatory.
    How do you comments those:

    1. Hi,

      Both of the links show that high levels of sugar are bad for the immune system. No one denies that. The problem is that, at least in the studies you mentioned, they showed decreased activity of some immune cells. This means decreased inflammation (less reactivity towards pathogens). If the immune system is depressed, T cells, mast cells, macrophages and other effector cells can't produce an adequate inflammatory response for containing infection.

      When referring to "inflammation", I meant the impact of the ingestion of a given food on the production of cytokines by immune (and fat) cells.

      Your link:

      Shows decreased phagocytosis, which means decreased inflammation produced by cells to destroy the pathogen ingested.

      The other link:

      Shows that fructose potentially depresses the normal response against S.aureus, by interferring with recognition mediated by MBL.

      So in any case, your study show an anti-inflammatory effect of high sugar in a scenario when you need a pro-inflammatory response.

    2. Indeed. Thx for clarifying.

    3. TwitchyFirefly

      "So in any case, your study show an anti-inflammatory effect of high sugar in a scenario when you need a pro-inflammatory response."

      Does this have any possible relevance to someone who has an autoimmune disease (a peripheral neuropathy, not diabetes) and has been very-low-carb, and mostly in ketosis, for over a year?

    4. Not really, the studies show effects on phagocytosis, which is a normal response against pathogens. On the contrary, hyperglycemia, because of the metabolic signature of T-cells, seem to promote effector differentiation and proliferation and inhibition of Treg differentiation/proliferation.

  10. Anonymous

    I am about to commence radiotherapy (with concurrent single agent (cisplatin) sensitizing chemotherapy) for HPV-P16 positive SCC of the head and neck. The cancer has no known primary and the single metastatic neck node has been removed, leaving no known tumor but a guess that the primary, based on the HPV, is likely in the oropharynx and that there are likely microscopic SCC cells in the neck that are better assaulted now than later.

    A key therapeutic concern is said to be the maintenance of a normal nitrogen balance through a high protein diet to support restoration of therapy-damaged normal tissues and bone marrow. Yet this cancer may be inhibited by a low calorie, low CHO/glucose diet, such as that I've been using very successfully in response to a pre-diabetes diagnosis (delivered simultaneously with what became the cancer diagnosis).

    Try as I might, but greatly hampered by any fundamental scientific training, I can't sort out the proper dietary balance here. Any thoughts would be welcome.

    Thank you.

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