Blog

Nomenclature

I dislike every currently-used term to describe a diet composed of “only” “animal foods”.

“Zero carb”? It’s not literally zero carb, particularly if you eat stuff like liver and eggs. Nevermind dairy or honey.

“Carnivore”? Even disregarding the phylogenic classification (the order Carnivora does not consist solely of meat-eating animals), even an animal that consumes a diet composed of less than 30% meat (by calories? by weight? who cares?) is considered a carnivore.

“Meat-based keto”? That’s only the low-protein version. “Meat-based low-carb”? That could mean eating your meat with lower than usual amounts of bread.

“Meat-only diet”? It’s not meat only. Eggs are acceptable, maybe dairy, too. Those aren’t meat. Don’t get me started on the classification of fish.

“Animal foods only diet”? “Plant-free diet”? That would sound good except apparently people find coffee and tea acceptable. Those are plant-derived.

And that’s not even getting into stuff like inherent unreliability of dietary anecdotes. I have no idea what exceptions to the general rule people find acceptable and which they don’t. Maybe there’s someone out there who thinks Mountain Dew is perfectly fine to drink while claiming to be “strict carnivore”.

I can only describe what I, myself, eat and disregard grumbling about definitions.

Review: The Case for Keto by Gary Taubes

Disclosures

I am biased against journalists, Gary Taubes in particular (due to his stated unwillingness to change his mind1,2) and his model of obesity (doesn’t work for me). I am biased in favor of low-carbohydrate diets, however.

General impression

The book is quite readable, and Taubes is a skilled wordsmith. The pacing is good, and repetition is kept at a tolerable level. I’d say it’s about as good, writing-wise, as Atkins’ first book4, better than Atkins’ second book5 – but decidedly inferior to the Drinking Man’s Diet6.

If someone without any nutritional knowledge whatsoever picked this book up, they would probably find the narrative compelling, the advice to be reasonably clear, and would, in turn, probably lose weight if not already constitutionally thin. Probably being a key word – to my knowledge, there is no ad libitum diet, even in clinical conditions of near-perfect adherence, that works to reduce everyone. Even when you exclude intractable cases like congenital leptin deficiency7, pituary tumours8 and the like. At best you can hope that the average person slims down a bit, and some people on one tail of the distribution drop weight like a stone35.

The biggest problem in the book is Taubes’ continued adherence to the Carbohydrate-Insulin hypothesis of obesity. In my opinion, Taubes would do himself a great favor by never mentioning insulin or carbohydrates being uniquely fattening again, and instead focusing on aspects of the LCHF diet that he can actually prove – or at least those that aren’t at stark odds with mountains of evidence to the contrary, including experiments specifically meant to test the hypothesis, funded in part by his own research organization. I don’t see why “you’ll be less hungry and lose weight” would be any less compelling than “your insulin will go down and you’ll lose weight” to someone who has no background in obesity research, such as the median self-help book reader. Yes, the problem is hormonal, but the hormone isn’t insulin18.

The unobjectionable

For all his faults, Taubes gets some things right – quite a few of them, and I’m surprised how much overlap there is between his book and The Hungry Brain34 by Dr Stephan Guyenet – in my opinion, of course, although I do try to have solid backing for my opinions. I have tried to interpret Taubes’ statements, if they were ambiguous, in a way that matches evidence.

  • Attempts to turn obese people into lean people have met, as yet, with resounding failure13,14,15 – neither diets nor exercise16 work in the long term, and usually don’t work in the short term either – at best you can produce temporarily reduced obese people. You would be hard-pressed to find anyone remotely informed, establishment nutritionist or not, who disputes this. The most effective, if also most drastic solution to obesity we currently possess is bariatric surgery17, and even that may not stick.
  • Eating behaviour is clearly driven by unconscious forces18. Calorie and energy balance calculations are a research tool, not an effective strategy for durable weight loss. I know of no evidence whatsoever of an outpatient dietary treatment of any kind that transforms the typical obese person into a lean person permanently.
  • Obesity has a strong genetic component19, at least as much as other strongly heritable traits like height or intelligence. In a premodern environment18, very few genetically susceptible people had the opportunity to manifest the obese phenotype, however. With highly convenient, delicious and cheap foods available, the impact of genes of obesity is maximized30.
  • Low-carbohydrate diets on an ad libitum basis do work for weight loss at least as well as any other dietary intervention20,21, perhaps slightly more so. If there is to be something like dietary guidelines, this kind of diet should be an option, rather than rigidly prescribing a moderately low-fat, high-CHO diet as they presently do.
  • Obesity is chiefly a hormonal issue18, not a behavioural one. The lean and obese don’t have vastly different psychological traits22,36. It’s just that the obese seem to target a fat mass that is vastly greater than with the lean23, which target they reach and sustain by eating more.
  • Not being an uncontrolled diabetic or highly insulin-resistant is probably far more important than maintaining ideal LDL levels24,25,26.
  • Ultra-processed junk foods and liquid calories, whether alcoholic or not, are enemies of maintaining one’s weight27. These are not, in general, foods to which we are particularly well adapted evolutionarily, for want of adequate exposure time to do so. Even a neolithic diet of mostly grain would probably be healthier than what people normally eat and drink.
  • What is regarded as healthy is in large part backed by nutritional epidemiology, which is chiefly based on self-reports, and those are not valid scientific instruments28. This is weak evidence to be basing national guidelines on.
  • Voluntary or externally involuntary overfeeding29 is not the cause of common obesity. In overfeeding trials, subjects tend to fairly quickly return to their normal weights, whatever they were.

The objectionable

There is only one claim in the book that I would strongly object to – aside from fairly trivial things like the definition of ‘tautology’ (not quite33 the same thing as ‘circular logic’, but fair enough) or whether Dr Ted Naiman32 and Dr Blake Donaldson31 advocated LCHF or ketogenic eating (don’t and didn’t, respectively; they’re not against it, but they’re at best adjacent) or unverifiable assertions about the psychology of obesity researchers (painted as somewhat dumb and malevolent in TCFK), and that is the Carbohydrate-Insulin model of obesity, paraphrased:

Carbohydrate is uniquely fattening because among macronutrients it has the greatest insulin response on ingestion.

This is inconsistent with reality, as shown by Guyenet with his mountain of citations3 for the 2019 debate (a painful thing to watch). The arguments there are as valid today as they were then, and more evidence9,10 has surfaced that makes this model even less likely than it was before (to be fair, there was also one piece of potentially supportive material11, but that one may have measurement issues12). Taubes is nothing if not tenacious and capable of raising both attention and funds to run clinical trials. The only thing missing now is a ketogenic overfeeding trial to put the final nail in this coffin.

Continued belief in this perplexes me. This model doesn’t have to be even remotely true for low-carbohydrate diets, ketogenic or not, high-fat or not, to work. Just about the only use for it I can think of is making rubes feel special, and drive adherence through zealotry. In my view, it’s another “Fat Mobilizing Hormone” (a hypothetical factor that Atkins mentioned in his book4, which turned out not to exist; Taubes even mentions it in TCFK) that opponents can use to discredit the dietary framework.

Conclusions

Overall, I think the advice contained in this book is healthy, and I will not be applying for a refund (not just because I don’t want to doxx myself). Just ignore the attempts to explain the mechanism of operation. You don’t need to know it for things to work, and you’re better off reading Guyenet’s The Hungry Brain34 if you really do want to know a thing or two about adiposity regulation.

References

  1. MAY 20, 2015 by STEPHENHOW, Gary Taubes vs. Alan Aragon EPIC Debate. Original URL: https://2lbsofstarch.com/2015/05/20/gary-taubes-vs-alan-aragon-epic-debate/
  2. SCIENCE, STORIES, AND SIDE-STEPPING: THE STEPHAN GUYENET VS. GARY TAUBES DEBATE. WRITTEN BY: LAYNE NORTON. APRIL 4TH, 2019. Original URL: https://www.biolayne.com/articles/research/science-stories-and-side-stepping-the-stephan-guyenet-vs-gary-taubes-debate/
  3. References for my debate with Gary Taubes on The Joe Rogan Experience. March 19, 2019 by Stephan Guyenet. Original URL: http://www.stephanguyenet.com/references-for-my-debate-with-gary-taubes-on-the-joe-rogan-experience/
  4. Atkins, Robert C. Dr. Atkins’ Diet Revolution Bantam, 1972.
  5. Atkins, Robert C. Dr. Atkins’ New Diet Revolution M. Evans and Company, 1992.
  6. Cameron, Robert. The Drinking Man’s Diet. Cameron Books; Revised ed. edition (June 1, 1964).
  7. Paz-Filho G, Mastronardi C, Delibasi T, Wong ML, Licinio J. Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy. Arq Bras Endocrinol Metabol. 2010;54(8):690-697. doi:10.1590/s0004-27302010000800005
  8. Müller HL. Craniopharyngioma. Handb Clin Neurol. 2014;124:235-53. doi: 10.1016/B978-0-444-59602-4.00016-2. PMID: 25248591.
  9. Hall, K. D., Guo, J., Courville, A. B., Boring, J., Brychta, R., Chen, K. Y., … Chung, S. T. (2020, May 6). A plant-based, low-fat diet decreases ad libitum energy intake compared to an animal-based, ketogenic diet: An inpatient randomized controlled trial. https://doi.org/10.31232/osf.io/rdjfb
  10. Hall, K.D., Guo, J. & Speakman, J.R. Do low-carbohydrate diets increase energy expenditure?. Int J Obes 43, 2350–2354 (2019). https://doi.org/10.1038/s41366-019-0456-3
  11. David S Ludwig, Stephanie L Dickinson, Beate Henschel, Cara B Ebbeling, David B Allison, Do Lower-Carbohydrate Diets Increase Total Energy Expenditure? An Updated and Reanalyzed Meta-Analysis of 29 Controlled-Feeding Studies, The Journal of Nutrition, , nxaa350, https://doi.org/10.1093/jn/nxaa350
  12. Tweet from Dr Kevin Hall. Original URL: https://twitter.com/KevinH_PhD/status/1334905961220206595
  13. Fildes A, Charlton J, Rudisill C, Littlejohns P, Prevost AT, Gulliford MC. Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records. Am J Public Health. 2015;105(9):e54–e59. doi:10.2105/AJPH.2015.302773
  14. Clinical Psychology Review. Volume 11, Issue 6, 1991, Pages 729-780. Confronting the failure of behavioral and dietary treatments for obesity. David M.GarnerSusan C.Wooley https://doi.org/10.1016/0272-7358(91)90128-H
  15. Mann, T., Tomiyama, A., Westling, E., Lew, A., Samuels, B., & Chatman, J. (2007). Medicare’s search for effective obesity treatments: diets are not the answer. The American psychologist, 62(3), 220-233. http://dx.doi.org/10.1037/0003-066x.62.3.220 Retrieved from https://escholarship.org/uc/item/2811g3r3
  16. Franz, Marion & VanWormer, Jeffrey & Crain, A Lauren & Boucher, Jackie & Histon, Trina & Caplan, William & Bowman, Jill & Pronk, Nicolaas. (2007). Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Weight-Loss Clinical Trials with a Minimum 1-Year Follow-Up. Journal of the American Dietetic Association. 107. 1755-67. 10.1016/j.jada.2007.07.017.
  17. O’Brien PE, Hindle A, Brennan L, et al. Long-Term Outcomes After Bariatric Surgery: a Systematic Review and Meta-analysis of Weight Loss at 10 or More Years for All Bariatric Procedures and a Single-Centre Review of 20-Year Outcomes After Adjustable Gastric Banding. Obes Surg. 2019;29(1):3-14. doi:10.1007/s11695-018-3525-0
  18. Lund J, Lund C, Morville T, Clemmensen C. The unidentified hormonal defense against weight gain. PLoS Biol. 2020;18(2):e3000629. Published 2020 Feb 25. doi:10.1371/journal.pbio.3000629
  19. Elks CE, den Hoed M, Zhao JH, et al. Variability in the heritability of body mass index: a systematic review and meta-regression. Front Endocrinol (Lausanne). 2012;3:29. Published 2012 Feb 28. doi:10.3389/fendo.2012.00029
  20. Johnston BC, Kanters S, Bandayrel K, et al. Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults: A Meta-analysis. JAMA. 2014;312(9):923–933. doi:10.1001/jama.2014.10397
  21. Ge Long, Sadeghirad Behnam, Ball Geoff D C, da Costa Bruno R, Hitchcock Christine L, Svendrovski Anton et al. Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials BMJ 2020; 369 :m696
  22. A FAILURE TO FIND DISTINCTIVE PERSONALITY FEATURES IN A GROUP OF OBESE MEN. NORRIS WEINBERG, MYER MENDELSON, and ALBERT STUNKARD. Published Online: 1 Apr 2006. https://doi.org/10.1176/ajp.117.11.1035
  23. Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. 2017;152(7):1718-1727.e3. doi:10.1053/j.gastro.2017.01.052
  24. García RG, Rincón MY, Arenas WD, Silva SY, Reyes LM, Ruiz SL, Ramirez F, Camacho PA, Luengas C, Saaibi JF, Balestrini S, Morillo C, López-Jaramillo P. Hyperinsulinemia is a predictor of new cardiovascular events in Colombian patients with a first myocardial infarction. Int J Cardiol. 2011 Apr 1;148(1):85-90. doi: 10.1016/j.ijcard.2009.10.030. Epub 2009 Nov 17. PMID: 19923024.
  25. Jeannie Yip, Francesco S. Facchini, Gerald M. Reaven, Resistance to Insulin-Mediated Glucose Disposal as a Predictor of Cardiovascular Disease, The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 8, 1 August 1998, Pages 2773–2776, https://doi.org/10.1210/jcem.83.8.5005
  26. Francesco S. Facchini, Nancy Hua, Fahim Abbasi, Gerald M. Reaven, Insulin Resistance as a Predictor of Age-Related Diseases, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 8, 1 August 2001, Pages 3574–3578, https://doi.org/10.1210/jcem.86.8.7763
  27. Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, Chung ST, Costa E, Courville A, Darcey V, Fletcher LA, Forde CG, Gharib AM, Guo J, Howard R, Joseph PV, McGehee S, Ouwerkerk R, Raisinger K, Rozga I, Stagliano M, Walter M, Walter PJ, Yang S, Zhou M. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metab. 2019 Jul 2;30(1):67-77.e3. doi: 10.1016/j.cmet.2019.05.008. Epub 2019 May 16. Erratum in: Cell Metab. 2019 Jul 2;30(1):226. Erratum in: Cell Metab. 2020 Oct 6;32(4):690. PMID: 31105044.
  28. Archer E, Pavela G, Lavie CJ. The Inadmissibility of What We Eat in America and NHANES Dietary Data in Nutrition and Obesity Research and the Scientific Formulation of National Dietary Guidelines. Mayo Clin Proc. 2015;90(7):911-926. doi:10.1016/j.mayocp.2015.04.009
  29. Obesity Reviews. The biology of human overfeeding: A systematic review. George A. Bray, Claude Bouchard. First published: 08 June 2020. https://doi.org/10.1111/obr.13040
  30. Komlos, John and Brabec, Marek, The Trend of BMI Values Among US Adults (March 2010). CESifo Working Paper Series No. 2987, Available at SSRN: https://ssrn.com/abstract=1573500
  31. Donaldson, Blake. Strong Medicine. Literary Licensing, LLC (July 21, 2012).
  32. Naiman, Ted. The PE Diet: Leverage your biology to achieve optimal health. November 1, 2019.
  33. Miriam-Webster Dictionary on tautology. Original URL: https://www.merriam-webster.com/dictionary/tautology
  34. Guyenet, Stephan. The Hungry Brain: Outsmarting the Instincts That Make Us Overeat. Flatiron Books (February 7, 2017).
  35. Gardner CD, Trepanowski JF, Del Gobbo LC, et al. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. JAMA. 2018;319(7):667–679. doi:10.1001/jama.2018.0245
  36. Is Dietary Nonadherence Unique to Obesity and Weight Loss? Results From a Randomized Clinical Trial. Emma J. Stinson Paolo Piaggi Susanne B. Votruba Colleen Venti Barbara Lovato‐Morales Scott Engel Jonathan Krakoff Marci E. Gluck. First published: 17 August 2020 https://doi.org/10.1002/oby.23008

Strong Medicine

I’ve recently read Blake Donaldson’s book, “Strong Medicine”. A very interesting book, to be sure, hilarious at times, with a mix of cunning observations and outdated scientific propositions.

First of all, the man is a tremendous shitlord and darwinist. Consider some of these quotes:

“Dispensary” probably means “public dispensary”, and the patients in question are poor people.
To a woman who got fat and her husband started sleeping around.
On allegies.
On what to do about alcoholism.
Medical technology’s deleterious effect on human health.

Donaldson is known for his all-meat diets, but that’s not exactly what he proposes. All-meat is his go-to for simple obesity, but for other things, he allows several other things to go with the meat (at least optionally). If anything, his stance is very Paleo, starting with observations on the state of dental health of primitive peoples:

The kind of foods he found to be adequate, besides fatty meat, are tubers, a limited variety of vegetables and fruits. He identified the chief problem foods as:

Still, there’s apparently nothing wrong with eating just meat:

Donaldson has a fair amount of opinions that are quite strange, but aren’t obviously wrong (such as the suggestion that smoking doesn’t cause cancer). His stance on salt is basically “never eat any” (reasonable from a Paleo template viewpoint), same as his opinion of eggs (which are kind of a gray area with Paleo thinking) and his stance on coffee is “drink exactly three half-cups per day”. The latter might be simply a reflection of the times and the culture of the land.

Overall, it’s a good book, which I recommend anyone interested in nutrition to read.

Finally, a collection of quotes I found noteworthy or funny:

How did these become popular? Could be that Donaldson is just weird.
Doubly true a century later.
I can confirm that eating too much cheese causes constipation. It’s probably the low water content.
More shitlording.
Therapy for an underweight patient.
This is probably even truer now. Yet people take even more vitamin pills.
Karen sighting.
General allergy treatment.
Amusing, yet important – savages don’t drink milk, yet have good teeth.
More allergy treatment.
The darwinism is strong with this one.
Demolishing myths.
Interesting. PUFA at work?
Interestingly, time restricted eating is largely unimportant in Donaldson’s view.
The one thing that troubles me greatly is the egg indictment.
Insanity that is mainstream thought to this day.
I confirm this. Too little fat – constipation. Too much – diarrhea.
On low-calorie diets.
The basic treatment.
Full agreement here – people can’t follow orders. Especially orders that don’t make sense to them.

Pre-carnivorous diet

If you ever wondered how I ate before I adopted a carnivorous diet, here’s my recollection of what I might eat on a typical day or three.

These are all recollection-based of what I was doing about four years ago, so take it with a huge grain of salt. Any criticism that applies to food frequency questionnaires applies here twofold. If anything, I probably underestimated how much I ate in a given day, by filtering out snacks and exact amounts.

Almost everyone is metabolically ill

Originally posted on Wykop here.

Prevalence of optimal metabolic health in America

At least if you’re American. Only about 1 in 8 people are metabolically healthy, by the metric of having none of the classic signs of metabolic syndrome (central obesity, hyperglycemia, hypertension, high triglicerides, low HDL). What’s even more interesting is that more than half of those who are underweight are metabolically unhealthy, suggesting that most of them are “skinny-fat”.

Source: Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016. Joana Araújo, Jianwen Cai, and June Stevens. Metabolic Syndrome and Related Disorders 2019 17:1, 46-52

Nutritional heretics

If you’ve ever wondered who Satan uses to advance his agenda of despoiling the human health condition, wonder no more – it’s the Seventh-Day Adventists. Aside from being heretics in the theological sense, which is the first clue that they’re doing something very wrong, they also somehow interpreted Scripture to suggest that people should be vegetarians, and they’ve spread their lies not only in the United States, but far beyond. Don’t take my word for it – they brag about it themselves.

I personally wonder how many of the American and global authorities on nutrition are SDA, or strongly influenced by them.

Reference:
Banta, J.E.; Lee, J.W.; Hodgkin, G.; Yi, Z.; Fanica, A.; Sabate, J. The Global Influence of the Seventh-Day Adventist Church on Diet. Religions20189, 251.

Fractionating butter

In light of the recent reports on saturated fat, especially stearic acid, I have decided to fractionate butter and see if it is any more satiating than regular butter. The first two attempts were somewhat unsuccessful; here I describe only the successful procedure.

Every natural fat is a mixture of different fatty acids. Depending on the proportions, the fat has a specific melting point. Fractionating fat, in this case butter, is dividing it into solid and liquid parts for a given temperature. The same process is used to produce MCT oil.

  1. Put a few sticks of butter into a pot.
  2. Melt them on low heat until fully melted.
  3. Let them cool for a few hours in room temperature.
  4. When it becomes a chunky, thick slop, filter it with a fine sieve. I used a protective sieve for frying pans.
  5. Collect the solid portion from the sieve, and then put it in the refrigerator. Do whatever you like with the liquid parts.
  6. The product will be finished when it cools down. You can compare it with the liquid by cooling both in separate containers. They will have different speeds of solidification.

Pictures:

Insulin resistance is physiological, chronic hyperinsulinemia is pathological

Insulin resistance – the reduced sensitivity to insulin signalling on a cellular level – is natural, expected and necessary when dealing with nutrient overload. Nutrient overload normally happens every time you eat a meal. In diabetics, they are in a state very similar to nutrient overload practically 24/7, which is why they commonly have elevated insulin (before their pancreas fails), both fasting and especially post-prandial. Blood sugar states are typically elevated only in late-stage diabetes, but triglicerides and free fatty acids are elevated long before then.

Individual cells have many, many mechanisms for avoiding both starvation and overfeeding. Neither is good for them. Insulin sensitivity modulation is one such mechanism, since one of insulin’s main jobs is to increase nutrient absorption into cells. The cell’s energy status determines its responsiveness to insulin, and this process is both quick and state-based, there’s no memory mechanism. Insulin is furthermore not required for all nutrient transport into the cell, there exist independent, gradient-based transporters. In a situation where the the cell has a lot of energy already in it, it will (and should) resist insulin’s effects. This is why we don’t suffer massive necrosis every time we eat a meal. This is also why diabetics get to survive for decades to be killed by chronic disease, rather than acute energy poisoning.

The pathology subsists in having a permanent energy overload, and this appears to be primarily a result of exceeding one’s genetically determined personal fat threshold. You can view it as the maximum storage capacity of your subcutaneous adipose tissue. The primary job of the adipose tissue is to provide an energy buffer – when you have fed, it needs to store excess energy, and when you are fasting, it needs to release energy back out so you don’t starve. But if that is full to the breaking point, adipocytes overstuffed, refusing to accept more lest they die of energy toxicity, that leaves an overabundance of energy in the bloodstream – fatty acids, triglicerides, glucose, even ketone bodies – which needs to be gotten out of there, lest it kill the subject in a matter of hours or days. Insulin is upregulated to deal with this problem. Nutrients are crammed everywhere they can be, particularly as ectopic fat, and cells get quite resistant to insulin, to preserve homeostasis with the highly increased levels being secreted.

This is bad for you in the long run, because the hormonal disregulation will give you chronic diseases, but at least it won’t kill you very fast, which is the alternative. The best cure for type 2 diabetes? Lose weight, doesn’t matter how. Particularly if you aren’t visibly obese, yet have blood markers suggesting diabetes.

Laron syndrome

I originally posted about this on Wykop here.

Laron syndrome is an interesting genetic defect. It results mainly in dwarfism and obesity, due to a mutant human growth hormone (HGH) receptor, which causes very low levels of insulin-like growth factor 1 (IGF1). Besides a whole lot of complications due to this, there is one thing, that happens very rarely to the affected – cancer. In comparison with heterozygotic, unaffected relatives, they have approximately a 95% reduction in cancer deaths.

This strongly suggests that cancer is a direct result of hyperinsulinemia: IGF1 receptors can bind with isulin, though with lower affinity, but with high concentrations, it’ll have to be at a higher rater than normal. People with Laron syndrome have very little IGF1 and normal insulin metabolism, and therefore low activity in this metabolic pathway. In turn, people without this mutation have normal IGF1 and normal insulin – if they acquire insulin resistance with hyperinsulinemia, IGF1 receptors will bind to insulin much more often, that it is supposed to happen.

Links:
Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer, ANNA JANECKA1⇑, MARTA KOŁODZIEJ-RZEPA2 and BEATA BIESAGA1, In Vivo July-August 2016 vol. 30 no. 4 375-381

Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans
BY JAIME GUEVARA-AGUIRRE, PRIYA BALASUBRAMANIAN, MARCO GUEVARA-AGUIRRE, MIN WEI, FEDERICA MADIA, CHIA-WEI CHENG, DAVID HWANG, ALEJANDRO MARTIN-MONTALVO, JANNETTE SAAVEDRA, SUE INGLES, RAFAEL DE CABO, PINCHAS COHEN, VALTER D. LONGO, SCIENCE TRANSLATIONAL MEDICINE16 FEB 2011 : 70RA13

Cianfarani S. Risk of cancer in patients treated with recombinant human growth hormone in childhood. Ann Pediatr Endocrinol Metab. 2019;24(2):92–98. doi:10.6065/apem.2019.24.2.92

Trends in Hyperinsulinemia Among Nondiabetic Adults in the U.S., Chaoyang Li, Earl S. Ford, Lisa C. McGuire, Ali H. Mokdad, Randie R. Little, Gerald M. Reaven, Diabetes Care Nov 2006, 29 (11) 2396-2402; DOI: 10.2337/dc06-0289

Endocr Pract. 2015 Dec;21(12):1395-402. doi: 10.4158/EP15939.RA. Epub 2015 Sep 24., LESSONS FROM 50 YEARS OF STUDY OF LARON SYNDROME., Laron Z.

Francesco S. Facchini, Nancy Hua, Fahim Abbasi, Gerald M. Reaven, Insulin Resistance as a Predictor of Age-Related Diseases, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 8, 1 August 2001, Pages 3574–3578, https://doi.org/10.1210/jcem.86.8.7763