252 SHARES Share Tweet

It’s easy to believe sugar is unhealthy, especially when you’re told that eating ‘too much’ of it, does bad things in your system, like helping to produce cholesterol. But cholesterol production being a bad thing, is only one of a long list of common health misunderstandings and misrepresentations.



When you live in a world where the ‘experts’ are constantly saying that high cholesterol is the cause of heart disease, and that the polyunsaturated fats (PUFAs) are a health food (in large part because of the fact that they can ‘lower’ cholesterol levels), then the idea that sugar is bad for your health, can easily start to sound like it must be legitimate.

And if you add to that, popular misconceptions about PUFAs being anti-inflammatory, essential, and generally disease protective, or theories suggesting excess sugar causes ‘adrenal fatigue’, or drains your energy, (not to mention even sillier ideas about sugar cravings being caused by ‘serotonin deficiencies’), you can be forgiven for thinking, that eating more PUFAs and avoiding sugar, makes sense.

Fortunately however, lots of high quality evidence exists, undermining the foundations underpinning these, and numerous related belief systems, belief systems which only really make sense in an upside down world.

For starters, many studies have shown the direct relationship between chronically and systemically high levels of cortisol, and the development of a significant number of degenerative diseases or inflammatory conditions.

“Cortisol is secreted by the adrenal cortex in response to stress…A number of studies have demonstrated that stress can disrupt neuroendocrine circadian rhythms in ways that favor tumor growth and metastasis.” (Moreno-Smith M, et al., 2010)

“There is increasing evidence that cortisol contributes to cardiovascular risk…Hypertension, truncal obesity, hyperglycemia, insulin resistance, and dyslipidemia are all important in this regard.” (Whitworth JA, et al., 2005)

Cortisol and catecholamines like adrenaline, tend to rise in response to excess stress (or under circumstances where there is insufficient sugar availability to meet demands) and experiments have shown that sugar (for eg. sucrose), can lower levels of cortisol and related stress substances.

Another experimentally demonstrated and long understood physiological principle, relates to the way in which excessive stress – leading to rising cortisol and adrenaline – promotes an increase in the release of free fatty acids out of storage. The breakdown products of the PUFAs (in particular), powerfully promote stress.

“Oxidized derivatives of linoleic acid have the potential to alter steroidogenesis….One such derivative is…(EKODE)…EKODE stimulates corticosterone biosynthesis and amplifies the effect of ACTH…Increased levels of fatty acid metabolites may be involved in the increased glucocorticoid production observed in obese humans.” (Bruder ED, et al., 2003)

Lots of good quality scientific studies have shown, that the release of fat into the blood stream, directly correlates with (or causes) the onset of inflammatory states which can promote conditions – such as diabetes, cardiovascular disease and cancer – often blamed on too much consumption of sugar.

“…elevated plasma levels of FFAs are not only a major cause of insulin resistance in skeletal muscle and liver but may, in addition, play a role in the pathogenesis of coronary artery disease.” (Boden G., 2003)

“These studies…identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells.” (Zeynep Madak-Erdogan, et al., 2019)

It is far more common today, for free fatty acids to be highly polyunsaturated in composition, and exposure to circulating PUFAs is one of the main causes of chronic systemic inflammation.

PUFAs are powerfully anti-thyroid or anti-metabolic, and a suppressed thyroid energy metabolism can be seen as being synonymous with stress, as well as being closely connected to the release of greater amounts of free fatty acids, all of which can promote the onset of a potentially downward spiraling inflammatory vicious circle-like state.

“…polyunsaturated dietary lipids such as those in corn oil activate Kupffer cells. This triggers production of oxidants and activation of NF-κB leading to synthesis of mitogenic cytokines such as TNFα which increases cell proliferation in parenchymal cells, causing promotion of previously initiated cells leading to tumors.” (Ivan Rusyn, et al., 1999)

“Breakdown of EPA and other UFAs [unsaturated fatty acids] by COX leads to the production of prostaglandins with LOX breakdown leading to the production of leukotrienes, and breakdown by CYP450 producing epoxyeicosatrienoic acid…all of which have been associated with pathology in a range of diseases including AD [Alzheimer disease]…” (Snowden SG, et al., 2017)

“…the anti-inflammatory effect of EFA [essential fatty acid] deficiency was more marked that that of dietary (n-3) fatty acid supplementation in acute inflammation.” (Lefkowith JB, et al., 1990)

Sufficient availability of sugar is necessary to improve thyroid function and energy metabolism (and to inhibit the release of the PUFAs from storage into the blood stream, increasing their reduction via safer methods), and this is one reason why it makes biological sense for sugar to be understood as an anti-inflammatory substance.

The suppression of thyroid metabolism, causes an increase in the release of cortisol as well as other inflammatory stress substances (like estrogen, serotonin and nitric oxide). Metabolic suppression also interferes with digestion in a number of ways, promoting bacterial overgrowth and an increase in exposure to (and systemic circulation of) bacterial endotoxin.

Many studies have shown a relationship between increased circulation of endotoxin (LPS) and the release of a variety of other substances which promote inflammation, such as serotonin for instance. Around 95% of serotonin is produced in the intestines, often in response to bacterial toxins and other poisonous substances. Endotoxin exposure has also been shown to have a direct inflammatory effect.

“…it is well known that humans are far more prone to disease pathology in the course of endotoxemia than mice…and we speculate that the functionality of an alternative inflammasome pathway in humans might in part be responsible for this phenomenon…”(Moritz M. Gaidt, et al., 2016)

“The observation of a direct effect of such highly substoichiometric amounts of LPS on both fibrinogen and coagulation can account for the role of very small numbers of dormant bacteria in disease progression in a great many inflammatory conditions…” (Etheresia Pretorius, et al., 2016)

Endotoxin and serotonin both promote estrogen production, and each of these, in excess, has the potential to interfere with liver function (preventing proper detoxification), furthering degeneration and inflammation, and encouraging the progression of many chronic stress related disease states, including cancer.

Funnily enough, cholesterol is known to play an important role in protection from infection and poison, and assists with the safe removal of endotoxin from the system. Increased cholesterol levels, have been demonstrated to be a predictor of longevity, and protection from disease in elderly populations. Low cholesterol on the other hand, has proven to be connected to the worsening of many conditions including depression, heart failure and cancer.

“Hypocholesterolemia is an important observation following trauma…Cholesterol levels were also adversely affected by infection or organ system dysfunction…Because lipoproteins can bind and neutralize lipopolysaccharide, hypocholesterolemia can negatively impact outcome.” (Wilson RF, et al., 2003)

“Subjects with low TC [total cholesterol] levels…are at higher risk of dying even when many related factors have been taken into account…physicians may want to regard very low levels of cholesterol as potential warning signs of occult disease or as signals of rapidly declining health.” (Brescianini S, et al., 2003)

Although the polyunsaturated fats can interfere directly with cholesterol production, sugar consumption helps to protect against the release of PUFAs from storage into the blood. Sugar also helps to directly promote the production of cholesterol. By improving thyroid energy metabolism, the sufficient availability of sugar, can also support the conversion of cholesterol into the highly protective anti-aging hormones, pregnenolone, progesterone, DHEA and testosterone.

Increasing your intake of sugar (and lowering exposure to PUFAs) can reduce stress (and cortisol and catecholamine release), and can protect against the breakdown of muscle and other tissue, which takes place more during stress, as a means to providing a necessary supply of sugar energy for the body and brain.

At the same time, sugar (and the reduction of stress), protects against the release of inflammatory amino acids (such as tryptophan) into the blood stream, known to be able to promote faster degeneration and aging. High stress, and greater circulation of tryptophan, can lead to increased production and circulation of serotonin, (including increased levels of serotonin in the brain), which (contrary to popular opinion), is generally not a good thing.

“Unlike artificial sweeteners, sugar may provide the fuel needed to meet the energetic demands of stress, which may reduce the need for glucocorticoid-driven energy catabolism and mobilization of the body’s energy stores.” (Tryon MS, et al., 2015)

As mentioned earlier, in upside down world, there are those who are promoting the confusing and illogical idea, that ‘sugar cravings’ are the result of a deficiency of serotonin. From a physiological perspective, however, sufficient availability of sugar, to meet the demands of stress, is one of the important things that helps lower serotonin levels in the body, as well as in the brain.

Blood sugar dysregulation on the other hand, is likely to do the opposite, promoting stress, inflammation and serotonin levels. Blood sugar issues are most commonly caused by the things that occur when stress is high, and when sugar availability is interfered with. Looking at things this way, makes more sense of all the experimental science, which demonstrates the relationship between increased serotonin, and the development of many inflammation related conditions, including cancer, heart disease, depression and anxiety.

“Serotonin…(5-HT)…has an essential role in the regulation of emotion….Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety…” (Catherine A. Marcinkiewcz, et al., 2016)

“…serotonin is the first metabolite shown to be elevated in obesity that inhibits the activity of BAT [brown adipose tissue]…Thus, inhibiting Tph1[tryptophan hydroxylase 1]-derived serotonin may be effective in reversing obesity and related clinical disorders such as NAFLD and type 2 diabetes.” (Crane JD, et al., 2015)

“The strongest evidence of a connection between neurotransmitters and HVDs is the association between serotonin and carcinoid valve disease…5HT [serotonin] has been associated with pathological remodeling effects on mature heart valves. Several experiments with excess serotonin have demonstrated this.” (Elliott Goldberg, et al., 2017)

You will probably be surprised to find out, that the evidence, which attempts to show that increased sugar (for example sucrose and fructose) consumption, in modern diets, is responsible for the increasing incidence of NAFLD (Non Alcoholic Fatty Liver Disease) and related conditions, including obesity, diabetes, cancer or cardiovascular disease, is very weak.



“…our preliminary systematic review and meta-analysis does not support a NAFLD-inducing effect of fructose in isocaloric exchange for other carbohydrates at levels of exposure that are well above that found in Western diets.” (Chiu S, et al., 2014)

“On the basis of the current study, it cannot be concluded that a high-carbohydrate diet or increased percentage of total energy intake in the form of carbohydrates increases the odds of obesity. ” (Kurt Sartorius, et al., 2018)

Numerous high quality studies however, explain the physiological mechanisms which connect high cortisol, and excessive exposure to the polyunsaturated fats (among other things), to the onset of the inflammatory disease states. From a biological perspective, sufficient sugar availability to meet energy requirements, and lower stress, is far more likely to be protective here.

Sugar dysregulation seems to be commonly misunderstood to be the result of the consumption of too much sugar, but as stated earlier, this is not accurate. There is however, plenty of good science, explaining how the metabolic effects of ongoing and excessive stress (including thyroid dysfunction, high cortisol, increased exposure to endotoxin, serotonin, estrogen, nitric oxide, lactic acid, and the polyunsaturated free fatty acids) powerfully promote chronic hyperglycemia, and numerous other symptoms of diabetes.

“…interrelationships between adipose tissue, inflammation, and insulin resistance appear key to understanding type 2 diabetes risk…low-grade chronic systemic inflammation contributes to this risk…endotoxin may act as a mediator of inflammation…” (Harte AL, et al., 2012)

“Impaired glucose tolerance and type 2 diabetes affect ∼40% of all Americans over the age of 65, yet the pathogenesis of this age-associated deterioration in glucose metabolism is poorly understood…aging is also associated with a marked inability of mitochondria to switch from lipid to glucose oxidation on insulin stimulation, which may further contribute to dysregulated glucose and lipid metabolism…” (Kitt Falk Petersen, et al., 2015)

“…free fatty acids (FFA) are one important link between obesity, insulin resistance, and type 2 diabetes. Plasma FFA levels are elevated in most obese subjects, and physiological elevations of plasma FFA inhibit insulin-stimulated glucose uptake…which…will result in hyperglycemia and eventually in type 2 diabetes.” (Boden G. 1999)

Insufficient availability of sugar, under conditions of stress, promotes greater exposure to PUFAs, and taken together this is a powerful driver of hypothyroidism, bacterial endotoxin exposure, as well as rising levels of circulation of many other substances of stress. Real science examining the biochemical changes that occur during the progression of NAFLD, show these inflammatory stress related things, to be central causative factors.

“Oxidative stress plays an important role in the pathogenesis of chronic liver diseases. The plasma level of 8-isoprostane, a product of lipid peroxidation…8-Isoprostane values are elevated in patients with NAFLD…increased lipid peroxidation is involved in the pathogenesis of NAFLD…” (Konishi M, et al., 2006)

“Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Nonalcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia.” (Efstathiadou ZA, et al., 2018)

“Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls…As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.” (Harte AL, et al., 2010)

It has become popular to claim that sugar is to blame for disease, because blood sugar dysregulation often goes hand in hand with the stress state. This of course, is not accurate, and the fact that sugar is not being used effectively is not the fault of sugar. In fact, limiting sugar consumption can exacerbate all of the conditions that promote blood sugar issues and disease.

There is however, good reason to think that excessive intake of cereal grains and starch (or pure glucose), as well as the consumption of a variety of difficult to digest fibers, can promote bacterial issues, inflammation, thyroid dysfunction, and blood sugar dysregulation. This is far more likely, when combined with a diet high in PUFAs. If anything, the combination of PUFAs and starchy hard to digest carbs, rather than sugar per se, is probably responsible for many of the problems, which are mistakenly blamed on sucrose or fructose.

“…current findings indicate that sugary foods contribute minimally to ‘food dependence’ and increased risk of weight gain.” (Markus CR, et al., 2017)

I’m not a doctor or a scientist, but I have noticed that there are numerous ways to set up (and potentially misinterpret) an experiment, so as to make it appear as though sugar or fructose, is the culprit in disease. Alternatively, it has also become common practice, to ignore (or attempt to discredit) well performed studies, that show otherwise in a logical manner, so as to be able to continue to make such claims. Unfortunately, lots of people listen and believe.



A diet avoiding PUFAs (as well as possibly reducing fat intake in general under some circumstances) and restricting intake of starches and fibers – particularly many kinds of under cooked vegetables, grains, beans and legumes – providing sufficient protein from milk, cheese and gelatin, and plenty of sugar from sweet ripe juicy fruits, fruit juice, honey and white sugar, has been shown to be one physiologically rational approach to improving the metabolically stressful conditions, which have been unfairly blamed on sugar.

See more here

Endocrinology. 2001. Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis? Laugero KD, et al.

Am J Physiol Regul Integr Comp Physiol. 2003. An oxidized metabolite of linoleic acid stimulates corticosterone production by rat adrenal cells. Bruder ED, et al.

Endocr Rev. 2010. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Manco M, et al.

Crit Care. 2003 Dec;7(6):413-4. Hypocholesterolemia in sepsis and critically ill or injured patients. Wilson RF, Barletta JF, Tyburski JG.

Gastroenterology. 2011. The importance of the gastrointestinal tract in the control of bone mass accrual. Karsenty G, et al.

BMJ Open. 2018 Feb 8;8(2):e018449. Does high-carbohydrate intake lead to increased risk of obesity? A systematic review and meta-analysis. Sartorius K, Sartorius B, Madiba TE, Stefan C.

J Clin Endocrinol Metab. 2015 Jun;100(6):2239-47. Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body. Tryon MS, Stanhope KL, Epel ES, Mason AE, Brown R, Medici V, Havel PJ, Laugero KD.

J Pharmacol Exp Ther. 2011 Dec;339(3):790-8. Serotonin receptor type 3 antagonists improve obesity-associated fatty liver disease in mice. Haub S, Ritze Y, Ladel I, Saum K, Hubert A, Spruss A, Trautwein C, Bischoff SC.

PLoS Med. 2017 Mar 21;14(3):e1002266. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. Snowden SG, Ebshiana AA, Hye A, An Y, Pletnikova O, O’Brien R, Troncoso J, Legido-Quigley C, Thambisetty M.

Free Radic Res. 2012 Jun;46(6):758-65. Fatty liver induced by free radicals and lipid peroxidation. Morita M, Ishida N, Uchiyama K, Yamaguchi K, Itoh Y, Shichiri M, Yoshida Y, Hagihara Y, Naito Y, Yoshikawa T, Niki E.

Nat Med. 2015 Feb;21(2):166-72. Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Crane JD, Palanivel R, Mottillo EP, Bujak AL, Wang H, Ford RJ, Collins A, Blümer RM, Fullerton MD, Yabut JM, Kim JJ, Ghia JE, Hamza SM, Morrison KM, Schertzer JD, Dyck JR, Khan WI, Steinberg GR.

Redox Rep. 2013;18(4):127-33. The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis. Ucar F, Sezer S, Erdogan S, Akyol S, Armutcu F, Akyol O.

Diabetes Care. 2012 Feb;35(2):375-82. High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects. Harte AL, Varma MC, Tripathi G, McGee KC, Al-Daghri NM, Al-Attas OS, Sabico S, O’Hare JP, Ceriello A, Saravanan P, Kumar S, McTernan PG.

J Gastroenterol Hepatol. 2006 Dec;21(12):1821-5. Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane. Konishi M, Iwasa M, Araki J, Kobayashi Y, Katsuki A, Sumida Y, Nakagawa N, Kojima Y, Watanabe S, Adachi Y, Kaito M.

Eur J Clin Nutr. 2014. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Chiu S, et al.

Biol Lett. 2016 Jan;12(1):20150867. Energetics of stress: linking plasma cortisol levels to metabolic rate in mammals. Haase CG, Long AK, Gillooly JF.

Am J Med. 1986. Sucrose substitution in prevention and reversal of the fall in metabolic rate accompanying hypocaloric diets. Hendler RG, et al.

Cardiovasc Res. 2012 Jan 1;93(1):4-5. Roles of saturated vs. polyunsaturated fat in heart failure survival: not all fats are created equal. Halade GV, Jin YF, Lindsey ML.

PNAS 112 (36) 11330-11334. Effect of aging on muscle mitochondrial substrate utilization in humans. Kitt Falk Petersen, Katsutaro Morino, Tiago C. Alves, Richard G. Kibbey, Sylvie Dufour, Saki Sono, Peter S. Yoo, Gary W. Cline, and Gerald I. Shulman

Lipids Health Dis. 2017 May 25;16(1):97. Emulsifying dietary fat modulates postprandial endotoxemia associated with chylomicronemia in obese men: a pilot randomized crossover study. Vors C, Drai J, Pineau G, Laville M, Vidal H, Laugerette F, Michalski MC.

Diabetes Care 33(5): 991-997. Differential Effects of Cream, Glucose, and Orange Juice on Inflammation, Endotoxin, and the Expression of Toll-Like Receptor-4 and Suppressor of Cytokine Signaling-3. Rupali Deopurkar, PHD, Husam Ghanim, PHD, Jay Friedman, PHD, Sanaa Abuaysheh, BSC, Chang Ling Sia, BSC, Priya Mohanty, MD, Prabhakar Viswanathan, PHD, Ajay Chaudhuri, MD and Paresh Dandona, MD, PHD

J Hepatol. 2002 Jul;37(1):56-62. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases. Seki S, Kitada T, Yamada T, Sakaguchi H, Nakatani K, Wakasa K.

J Clin Invest. 2002 May;109(10):1321-6. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, Shulman GI.

Cell Metab. 2017 Feb 7;25(2):358-373. Prevention of dietary fat-fueled ketogenesis attenuates BRAF V600E tumor growth. Xia S, Lin R, Jin L, Zhao L, Kang HB, Pan Y, Liu S, Qian G, Qian Z, Konstantakou E, Zhang B, Dong JT, Chung YR, Abdel-Wahab O, Merghoub T, Zhou L, Kudchadkar RR, Lawson DH, Khoury HJ, Khuri FR, Boise LH, Lonial S, Lee BH, Pollack BP, Arbiser JL, Fan J, Lei QY, Chen J.

J Clin Invest. 2001 Aug;108(3):437-46. Prevention of fat-induced insulin resistance by salicylate. Kim JK, Kim YJ, Fillmore JJ, Chen Y, Moore I, Lee J, Yuan M, Li ZW, Karin M, Perret P, Shoelson SE, Shulman GI.

Future Oncol. 2010 Dec;6(12):1863-81. Impact of stress on cancer metastasis. Moreno-Smith M, Lutgendorf SK, Sood AK.

Gastroenterology. 2007 Aug;133(2):608-18. Serotonin Mediates Oxidative Stress and Mitochondrial Toxicity in a Murine Model of Nonalcoholic Steatohepatitis. Nocito A, Dahm F, Jochum W, Jang JH, Georgiev P, Bader M, Renner EL, Clavien PA.

Psychoneuroendocrinology. 2016 Sep;71:102-9. Executive functioning and diabetes: The role of anxious arousal and inflammation. Murdock KW, LeRoy AS, Lacourt TE, Duke DC, Heijnen CJ, Fagundes CP.

Front Endocrinol (Lausanne). 2017 Nov 29;8:335. Relationship between Hypothyroidism and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. He W, An X, Li L, Shao X, Li Q, Yao Q, Zhang JA.

J Immunol. 1990 Sep 1;145(5):1523-9.Manipulation of the acute inflammatory response by dietary polyunsaturated fatty acid modulation. Lefkowith JB, Morrison A, Lee V, Rogers M.

Scientific Reportsvolume 7, Article number: 17134 (2017). Effect of canola oil consumption on memory, synapse and neuropathology in the triple transgenic mouse model of Alzheimer’s disease. Elisabetta Lauretti & Domenico Praticò.

Minerva Endocrinol. 2018 Sep;43(3):367-376. Thyroid dysfunction and nonalcoholic fatty liver disease. Efstathiadou ZA, Kita MD, Polyzos SA.

JAMA Cardiol. 2018 Mar 1;3(3):225-234. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks. Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R; Omega-3 Treatment Trialists’ Collaboration.

J R Soc Interface. 2016 Sep;13(122). pii: 20160539. Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide. Pretorius E, Mbotwe S, Bester J, Robinson CJ, Kell DB.

Cell. 2015 Apr 9;161(2):264-76. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY.

Immunity. 2016 Apr 19;44(4):833-46. Human Monocytes Engage an Alternative Inflammasome Pathway. Gaidt MM, Ebert TS, Chauhan D, Schmidt T, Schmid-Burgk JL, Rapino F, Robertson AA, Cooper MA, Graf T, Hornung V.

Am J Physiol Regul Integr Comp Physiol. 2003 Jun;284(6):R1631-5. An oxidized metabolite of linoleic acid stimulates corticosterone production by rat adrenal cells. Bruder ED, Ball DL, Goodfriend TL, Raff H.

Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E9172-E9180. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N.

J Nutr Biochem. 2018 Feb;52:36-44. Gene pathways associated with mitochondrial function, oxidative stress and telomere length are differentially expressed in the liver of rats fed lifelong on virgin olive, sunflower or fish oils. Varela-Lopez A, Pérez-López MP, Ramirez-Tortosa CL, Battino M, Granados-Principal S, Ramirez-Tortosa MDC, Ochoa JJ, Vera-Ramirez L, Giampieri F, Quiles JL.

Nature Communications volume 5, Article number: 4924 (2014). Glucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice. Pavlos Missios, Yuan Zhou, Luis Miguel Guachalla, Guido von Figura, Andre Wegner, Sundaram Reddy Chakkarappan, Tina Binz, Anne Gompf, Götz Hartleben, Martin D. Burkhalter, Veronika Wulff, Cagatay Günes, Rui Wang Sattler, Zhangfa Song, Thomas Illig, Susanne Klaus, Bernhard O. Böhm, Tina Wenz, Karsten Hiller & K. Lenhard Rudolph

Am J Clin Nutr. 2010 Apr;91(4):940-9. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Ghanim H, Sia CL, Upadhyay M, Korzeniewski K, Viswanathan P, Abuaysheh S, Mohanty P, Dandona P.

J Inflamm (Lond). 2010 Mar 30;7:15. Elevated endotoxin levels in non-alcoholic fatty liver disease. Harte AL, da Silva NF, Creely SJ, McGee KC, Billyard T, Youssef-Elabd EM, Tripathi G, Ashour E, Abdalla MS, Sharada HM, Amin AI, Burt AD, Kumar S, Day CP, McTernan PG.

Birth Defects Res. 2018 Jul 3;110(11):901-909. Low carbohydrate diets may increase risk of neural tube defects. Desrosiers TA, Siega-Riz AM, Mosley BS, Meyer RE; National Birth Defects Prevention Study.

Am J Clin Nutr. 1989 Jun;49(6):1290-4. Dietary fructose or starch: effects on copper, zinc, iron, manganese, calcium, and magnesium balances in humans. Holbrook JT, Smith JC Jr, Reiser S.

J Am Geriatr Soc. 2003. Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging. Brescianini S, et al.

BMJ Open. 2016 Jun 12;6(6):e010401. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. Ravnskov U, Diamond DM, Hama R, Hamazaki T, Hammarskjöld B, Hynes N, Kendrick M, Langsjoen PH, Malhotra A, Mascitelli L, McCully KS, Ogushi Y, Okuyama H, Rosch PJ, Schersten T, Sultan S, Sundberg R.

Isr J Med Sci. 1996 Nov;32(11):1134-43. Review. Diet and disease–the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet. Yam D, Eliraz A, Berry EM.

Aliment Pharmacol Ther. 2017 Jul;46(2):175-182. Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease. Pang J, Xu W, Zhang X, Wong GL, Chan AW, Chan HY, Tse CH, Shu SS, Choi PC, Chan HL, Yu J, Wong VW.

PLoS Genet. 2018 Jan 10;14(1):e1007171. Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure. Salatzki J, Foryst-Ludwig A, Bentele K, Blumrich A, Smeir E, Ban Z, Brix S, Grune J, Beyhoff N, Klopfleisch R, Dunst S, Surma MA, Klose C, Rothe M, Heinzel FR, Krannich A, Kershaw EE, Beule D, Schulze PC, Marx N, Kintscher U.

Cell Mol Gastroenterol Hepatol. 2017 Apr 13;4(2):205-221. Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans. Chassaing B, Raja SM, Lewis JD, Srinivasan S, Gewirtz AT.

Diabetes. 2005 Dec;54(12):3458-65. Free Fatty Acids Produce Insulin Resistance and Activate the Proinflammatory Nuclear Factor-κB Pathway in Rat Liver. Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N.

Crit Care. 2010;14(1):R13. doi: 10.1186/cc8869. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury. Meierhans R, Béchir M, Ludwig S, Sommerfeld J, Brandi G, Haberthür C, Stocker R, Stover JF.

Exp Clin Endocrinol Diabetes. 2003 May;111(3):121-4. Review. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Boden G.

Transl Psychiatry. 2017 Jan 31;7(1):e1020. Glucose deficit triggers tau pathology and synaptic dysfunction in a tauopathy mouse model. Lauretti E, Li JG, Di Meco A, Praticò D.

Obes Sci Pract. 2015 Dec;1(2):126-130. Fast food, soft drink and candy intake is unrelated to body mass index for 95% of American adults. Just DR, Wansink B.

PNAS 106 (36) 15418-15423; Vascular effects of a low-carbohydrate high-protein diet. Shi Yin Foo, Eric R. Heller, Joanna Wykrzykowska, Christopher J. Sullivan, Jennifer J. Manning-Tobin, Kathryn J. Moore, Robert E. Gerszten, and Anthony Rosenzweig

Proc Assoc Am Physicians. 1999 May-Jun;111(3):241-8. Review. Free fatty acids, insulin resistance, and type 2 diabetes mellitus. Boden G.

Nature. 2017 Jan 5;541(7635):41-45. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Pascual G, Avgustinova A, Mejetta S, Martín M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, Bescós C, Di Croce L, Benitah SA.

N Engl J Med 2017; 377:1119-1131. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. Paul M Ridker, M.D., Brendan M. Everett, M.D., Tom Thuren, M.D., Jean G. MacFadyen, B.A., William H. Chang, Ph.D., Christie Ballantyne, M.D., Francisco Fonseca, M.D., Jose Nicolau, M.D., Wolfgang Koenig, M.D., Stefan D. Anker, M.D., John J.P. Kastelein, M.D., Jan H. Cornel, M.D.,

J Clin Invest. 1996 Jun 15;97(12):2859-65. Mechanism of free fatty acid-induced insulin resistance in humans. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI.

Nature. 2016 Oct 6;538(7623):109-113. The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila. Singh SR, Zeng X, Zhao J, Liu Y, Hou G, Liu H, Hou SX.

Nature volume 537, pages 97–101 (01 September 2016). Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala, Catherine A. Marcinkiewcz, Christopher M. Mazzone, Giuseppe D’Agostino, Lindsay R. Halladay, J. Andrew Hardaway, Jeffrey F. DiBerto, Montserrat Navarro, Nathan Burnham, Claudia Cristiano, Cayce E. Dorrier, Gregory J. Tipton, Charu Ramakrishnan, Tamas Kozicz, Karl Deisseroth, Todd E. Thiele, Zoe A. McElligott, Andrew Holmes, Lora K. Heisler & Thomas L. Kash

PLoS One. 2013;8(1):e55030. Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies. Noto H, Goto A, Tsujimoto T, Noda M.

Trends Neurosci. 2013 Oct;36(10):587-97. Sugar for the brain: the role of glucose in physiological and pathological brain function. Mergenthaler P, Lindauer U, Dienel GA, Meisel A.

J Clin Endocrinol Metab. 1996. Fasting as a metabolic stress paradigm selectively amplifies cortisol secretory burst mass and delays the time of maximal nyctohemeral cortisol concentrations in healthy men. Bergendahl M, et al.

Breast Cancer Researchvolume 19, Article number: 77 (2017). Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice. Nguyen M. Nguyen, Fabia de Oliveira Andrade, Lu Jin, Xiyuan Zhang, Madisa Macon, M. Idalia Cruz, Carlos Benitez, Bryan Wehrenberg, Chao Yin, Xiao Wang, Jianhua Xuan, Sonia de Assis & Leena Hilakivi-Clarke

J Clin Invest. 2010 Jan;120(1):142-56. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B, Kaluarachchi K, Bornmann W, Duvvuri S, Taegtmeyer H, Andreeff M.

Am J Physiol. 1987 May;252(5 Pt 2):R897-901. Polyunsaturated lipid diet lengthens torpor and reduces body temperature in a hibernator. Geiser F, Kenagy GJ.

Prog Clin Biol Res. 1983;111:89-109. Energy metabolism in trauma and sepsis: the role of fat. Wolfe RR, Shaw JH, Durkot MJ.

Appetite. 2017 Jul 1;114:64-72. Eating dependence and weight gain; no human evidence for a ‘sugar-addiction’ model of overweight. Markus CR, Rogers PJ, Brouns F, Schepers R.

Carcinogenesis, Volume 20, Issue 11, November 1999, Pages 2095–2100, Corn oil rapidly activates nuclear factor-κB in hepatic Kupffer cells by oxidant-dependent mechanisms. Ivan Rusyn, Cynthia A. Bradham, Leslie Cohn, Robert Schoonhoven, James A. Swenberg, David A. Brenner, Ronald G. Thurman

Physiol Rep. 2017 Feb;5(4). pii: e13171. Suppressed sympathetic outflow to skeletal muscle, muscle thermogenesis, and activity energy expenditure with calorie restriction. Almundarij TI, Gavini CK, Novak CM.

PLoS One. 2012;7(9):e46484. Inhibition of Fatty Acid Metabolism Reduces Human Myeloma Cells Proliferation. Tirado-Vélez JM, Joumady I, Sáez-Benito A, Cózar-Castellano I, Perdomo G.

Cell Cycle. 2012 Nov 1;11(21):3964-71. Ketone body utilization drives tumor growth and metastasis. Martinez-Outschoorn UE, Lin Z, Whitaker-Menezes D, Howell A, Sotgia F, Lisanti MP.

J Nutr Biochem. 2015 Apr;26(4):319-26. A high-fat diet rich in corn oil reduces spontaneous locomotor activity and induces insulin resistance in mice. Wong CK, Botta A, Pither J, Dai C, Gibson WT, Ghosh S.

Am J Clin Nutr. 2016 Mar;103(3):895-901. Associations of egg and cholesterol intakes with carotid intima-media thickness and risk of incident coronary artery disease according to apolipoprotein E phenotype in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Virtanen JK, Mursu J, Virtanen HE, Fogelholm M, Salonen JT, Koskinen TT, Voutilainen S, Tuomainen TP.

Vasc Health Risk Manag. 2005;1(4):291-9. Review. Cardiovascular Consequences of Cortisol Excess. Whitworth JA, Williamson PM, Mangos G, Kelly JJ.

Cancer Research March 12, 2019. Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling. Zeynep Madak-Erdogan, Shoham Band, Yiru Chen Zhao, Brandi Patrice Smith, Eylem Kulkoyluoglu-Cotul, Qianying Zuo, Ashlie Santaliz Casiano, Kinga Wrobel, Gianluigi Rossi, Rebecca Lee Smith, Sung Hoon Kim, John A. Katzenellenbogen, Mariah L Johnson, Meera Patel, Natascia Marino, Anna Maria V Storniolo and Jodi A Flaws

Cardiovascular Research, Volume 113, Issue 8, July 2017, Pages 849–857, Serotonin and catecholamines in the development and progression of heart valve diseases. Elliott Goldberg, Juan B. Grau, Jacqueline H. Fortier, Elisa Salvati, Robert J. Levy, Giovanni Ferrari

#sugarsaves

#thatpufafilm

#raypeat

Image: sweet666heart: “L and His Love For Sugar Cubes”