Fructose Is an Inflammatory Word

Inflammatory words arouse strong emotion. Related to our physical being, the term “inflammatory” refers to the body’s strong response to invasion by a foreign substance, such as a virus or bacterium, or to direct injury of tissue, both conditions stimulating the body’s attempt at self-protection with the ultimate goal of healing. Taking a closer look at the word “inflammation,” we see f-l-a-m, which suggests “flame.”  Now that you have the mental image, the defining characteristics of inflammation make sense—capillary dilation, leukocyte infiltration, redness, heat, and pain, all of which pull together to get rid of the damaging perpetrator.

Inflammation is not the same thing as infection, even when infection causes inflammation. Ongoing inflammation can self-perpetuate, particularly if there is a gene variant linked to it. If swelling is visible, our first reaction is to stop it, but not all inflammation is so apparent. This invisible inflammation, at the low end of the spectrum, is usually present for a long time and is termed “chronic.”  We know of its presence because it can be seen under a microscope or through specialized blood tests, such as highly-sensitive C-reactive protein or erythrocyte sedimentation rate (ESR). This inflammation, some believe, is the basis of degenerative diseases, including cardiovascular disease, diabetes, certain forms of cancer, Parkinson’s and Alzheimer’s, autoimmune diseases, and even wrinkled, sagging skin. Although inflammation is necessary for healing, it needs to stop once the healing is accomplished.

While there are drugs and over-the-counter medicines that can tame inflammation, they come with serious side effects when used long term. An easier solution is to reduce chronic inflammation through diet. Sugars are pro-inflammatory. Refined grains that cause glucose and insulin spikes are pro-inflammatory. Rancid, processed vegetable oils are pro-inflammatory. Processed foods and their trans-fats are pro-inflammatory. Among the most reliably pro-inflammatory molecules, though, is fructose. Common to soft drinks and fruit juices—and to the fruits from which they are extracted—sucrose puts people at risk for depleting their stores of critically important ATP (Abdelmalek, 2012), which provides energy for cellular processes. Unlike other simple sugars, fructose requires ATP for its metabolism, the depletion of which increases risk for inflammation, especially in the liver, where non-alcoholic fatty liver disease may follow (Ouyang, 2008). Additionally, Abdelmalek and colleagues determined that more uric acid is produced when excess fructose is consumed, increasing the odds for suffering gout, elevated blood pressure, type 2 diabetes, metabolic syndrome, and uric-acid- related kidney stones (Abdelmalek, 2012). The moderate intake of fructose from fresh fruits is not so much a concern because of their concomitant fiber and micronutrients.

Endothelial cells make up the thin layer of cells that line the interior of blood and lymphatic vessels. Vascular endothelial cells line the entire circulatory system, from the heart to the tiniest capillaries. Dysfunction of these cells sets the stage for vascular diseases, and is considered a key to the development of atherosclerosis. Such can be initiated by inflammation, which can be induced by fructose (Glushakova, 2008). The response to fructose might also include a cascade of events that leads to the progression of kidney disease and the incidence of metabolic syndrome (Choi, 2009). Where kidneys are concerned, control of blood pressure is important, since the angiotensin-renin system depends upon the kidneys for regulation and adjustment of arterial pressure. A diet low in fructose improves blood pressure and inflammatory markers, especially for those whose lifestyles or genetics increase risk for kidney disease (Brymora, 2012).

Fructose is absorbed directly by the intestine. If combined with glucose, as it is in table sugar (sucrose), enzymes will separate it and it will be absorbed like free fructose. It gets taken up by the liver and does not require insulin for metabolism, so it is not burned inside cells. It does get stored as fat, though, and does increase triglycerides (Kaumi, 1996). But it’s hard to imagine fructose being related to kidney stones.  Sparked by an interest in the burgeoning consumption of fructose in recent decades, researchers at Harvard found that fructose increases the urinary excretion of oxalates, uric acid and other factors associated with kidney stone formation. Though the fructose bound to glucose in table sugar was not exculpated, the freed fructose is independently associated with increased risk for stones (Taylor, 2008) (Cirillo, 2009).

For those so inclined, addictions share cross-overs much as training regimens do for athletes.  Alcohol dependence has not only genetic factors, but also psychosocial and environmental factors that can lead to prolonged periods of heavy alcohol consumption.  Sooner or later, withdrawal symptoms telegraph physical dependence, which instigates a variety of social and/or legal problems. Children adopted away from an alcoholic history still have the risk. Fructose is fermentable to ethanol. Close observation of fructose metabolism in the liver and activity in the brain shows parallelism with ethanol. First, both serve as substrates for lipid manufacture and the promotion of hepatic insulin resistance, dyslipidemia and steatosis. Second, fructose will cross-link with proteins to form acetaldehyde, which is an intermediate in the metabolism of alcohol that causes headaches and irritation to mucous membranes, among other disasters. But the third common element might be the worst. The hedonic center of the brain is stimulated by fructose in the same manner as alcohol, creating habituation and maybe even dependence (Lustig, 2010) (Byerley, 2010). Obesity is not an innocuous sequela to fructose overdose. But a least there are no traffic tickets for driving fat.

Triglycerides go up. Advanced glycation end products make cell membranes brittle and dysfunctional. Inflamed kidneys respond by forming stones. Blood pressure may rise. The liver collects fatty deposits made from triglycerides. Insulin resistance can lead to type 2 diabetes. Inflammation by fructose.

Some of the people you see are walking masses of inflammation, a maelstrom of metabolic mélange modulated by mouth. We might not have the right to intervene, but we can set an example.

Abdelmalek MF, Lazo M, Horska A, Bonekamp S, Lipkin EW, Balasubramanyam A, Bantle JP, et al Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes. Hepatology. 2012 Sep;56(3):952-60.

Benetti E, Mastrocola R, Rogazzo M, Chiazza F, Aragno M, Fantozzi R, Collino M, Minetto MA. High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR- δ Agonism. Mediators Inflamm. 2013;2013:509502.

Andrzej Brymora, Mariusz Flisiński, Richard J. Johnson, Grażzyna Goszka, Anna Stefańska, Jacek Manitius Low-fructose Diet Lowers Blood Pressure and Inflammation in Patients With Chronic Kidney Disease Nephrol Dial Transplant. 2012;27(2):608-612.

Byerley LO, Lee WN. Are ethanol and fructose similar? J Am Diet Assoc. 2010 Sep;110(9):1300-1.

Hyon K Choi, Gary Curhan Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study BMJ 2008;336:309

Mary E. Choi The Not-so-Sweet Side of Fructose JASN. March 2009; vol. 20 no. 3: 457-459

Cirillo P, Gersch MS, Mu W, Scherer PM, Kim KM, Gesualdo L, Henderson GN, Johnson RJ, Sautin YY. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol. 2009 Mar;20(3):545-53.

Collino M, Benetti E, Rogazzo M, Mastrocola R, Yaqoob MM, Aragno M, Thiemermann C, Fantozzi R. Reversal of the deleterious effects of chronic dietary HFCS-55 intake by PPAR-δ agonism correlates with impaired NLRP3 inflammasome activation. Biochem Pharmacol. 2013 Jan 15;85(2):257-64.

Glushakova O, Kosugi T, Roncal C, Mu W, Heinig M, Cirillo P, Sánchez-Lozada LG, et al Fructose induces the inflammatory molecule ICAM-1 in endothelial cells. J Am Soc Nephrol. 2008 Sep;19(9):1712-20.

Helen Hermana M Hermsdorff, María Ángeles Zulet, Blanca Puchau and José Alfredo Martínez Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study Nutrition & Metabolism 2010, 7:42

Chidambaram Jaya, Vetriselvi Venkatesan­, Carani Venkatraman Anuradha Inflammatory responses in liver induced by high fat plus fructose diet: therapeutic potential of cissus quadrangularis stem Int J Biol Med Res. 2010; 1(4): 120 – 124

Johnson RJ, Sanchez-Lozada LG, Nakagawa T. The effect of fructose on renal biology and disease. J Am Soc Nephrol. 2010 Dec;21(12):2036-9.

Kaumi T, Hirano T, Odaka H, Ebara T, Amano N, Hozumi T, Ishida Y, Yoshino G. VLDL triglyceride kinetics in Wistar fatty rats, an animal model of NIDDM: effects of dietary fructose alone or in combination with pioglitazone. Diabetes. 1996 Jun;45(6):806-11.

Lê KA, Tappy L. Metabolic effects of fructose. Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):469-75.

Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010 Sep;110(9):1307-21.

Mattioli LF, Thomas JH, Holloway NB, Schropp KP, Wood JG. Effects of intragastric fructose and dextrose on mesenteric microvascular inflammation and postprandial hyperemia in the rat. JPEN J Parenter Enteral Nutr. 2011 Mar;35(2):223-8.

Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, Johnson RJ, Abdelmalek MF. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008 Jun;48(6):993-9.

Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. Magnes Res. 2006 Dec;19(4):237-43.

Seaman DR. The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? J Manipulative Physiol Ther. 2002 Mar-Apr;25(3):168-79.

Taylor EN, Curhan GC. Fructose consumption and the risk of kidney stones. Kidney Int. 2008 Jan;73(2):207-12.

*These statements have not been evaluated by the FDA. These products are not intended to treat, diagnose, cure, or prevent any disease.