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Diabetes and Omega-3’s

Diabetes, Omega-3 fatty acids Super FoodsReading, interpreting and understanding scientific literature can be tedious because the authors often find that their previous paper on the subject missed its mark or was completely wrong. Easy to do when you are blazing new trails; however, the caution they go through to cover their tracks oftentimes makes for difficult reading. Luc Djousse and his colleagues at the U of Washington reported in the May 18, 2011 edition of the American Journal of Clinical Nutrition that, “With the use of objective biomarkers, long-chain omega 3 Fatty Acids (FAs) and Alpha-Linolenic Acid (ALA) were not associated with a higher incidence of diabetes. Individuals with the highest concentrations of both types of FAs had lower risk of diabetes.”

Speed reading is absolutely out of place. Omega-3 fatty acids in the body help to control the inflammation process, which is a benefit because the start of the healing process—initiated by the omega-6 arachidonic acid—also involves the possibility of getting carried away with the exercise. Say you have a cut or abrasion. The key activity that ensues is to stop the loss of fluids – save the blood.  It is that process which tells the body to start the healing by sending white blood cells and platelets to the site of the wound and to agglomerate and close the exit door by swelling the tissues, which is also another way of looking at inflammation. To inflame can be life saving. The omega-3’s are then involved in the work of modulating the activity helping to ease the inflammation that comes with the correction process.

Fatty acids, especially those that are long and highly unsaturated, increase cell membrane fluidity and functionality. Fatty acids are essential to membrane activity at the location of hormone receptors. Insulin resistance in adult-onset diabetes is directly associated with fewer membrane enhancing long-chain fatty acids, largely due to impaired function of desaturase and elongase enzymes needed for a healthy membrane. Ruiz-Gutierrez 1993, “We have studied the fatty acid composition of erythrocyte membrane phospholipids in nine Type 1 (insulin-dependent) diabetic patients and nine healthy control subjects. Cell membranes from the diabetic patients showed a marked decrease in the total amount of polyunsaturated fatty acids mainly at the expense of docosahexaenoic acid, DHA, and arachidonic acid C20:4n6”.

Cell membrane abnormalities in lipid content are found to be related to poor metabolic control, which is a characteristic of diabetes. Diet is a very important  factor, and interventions with dietary essential fatty acids (EFAs) in the correct ratio (found to be 4:1, omega-6:omega-3), can make a difference. Decsif  T., 2002, “Reduced availability of long-chain polyunsaturates in diabetic children suggests that an enhanced dietary supply of long-chain polyunsaturates may be beneficial”. Children with diabetes demonstrate a deficit of long-chain fatty acids, so incorporating them into a child’s diet is prudent. An unspoken benefit in the application of EFA’s to diabetes treatment is the decrease in triglyceride levels, themselves striking indicators of the potential for cardiovascular issues and very often appearing in persons with diabetes.

Herein resides the prolonged physiological support of the EFAs. For those who lack the efficient conversion of the omega-3 alpha linolenic acid from plant sources (notably flaxseeds and their oil) to EPA and DHA, fish oil may be a viable alternative. In fact the the FA conversion process with diabetes is almost non-existent, but also common with aging.

For quite some time the essential fatty acids have been misunderstood. Of the types of fatty acids, the omega-3’s have received the most publicity, having been applauded for positive health effects, principally, because over the last century the general population ate little fish and had little or no n-3s in the diet. Unless they were more or less health nuts, few did not have any exposure to omega 3s as in flax, and even if they did their ability to elevate up to EPA and DHA was minimal. Fish oil was the answer but the explosion that ensued caused over-consumption and still does.

Hence the comments of Djousse et al that n-3 FAs did not increase diabetes but if both the omega 6s and the 3 s were added together there was marked improvements. There is an inference that n-3s were of no benefit and needed the balance of both EFAs, which we applaud and so should you. Balance is paramount.

References

Djoussé L, Biggs ML, Lemaitre RN, King IB, Song X, Ix JH, Mukamal KJ, Siscovick DS, Mozaffarian D. Plasma omega-3 fatty acids and incident diabetes in older adults. Am J Clin Nutr. 2011 May 18.

Ruiz-Gutierrez V, Stiefel P, Villar J, García-Donas MA, Acosta D, Carneado J.  Cell membrane fatty acid composition in type 1 (insulin-dependent) diabetic patients: relationship with sodium transport abnormalities and metabolic control.  Diabetologia. 1993 Sep;36(9):850-6.

T. Decsif, H. Minda, R. Hermann, A. Kozári, É. Erhardt, I. Burus, Sz. Molnár and Gy. Soltész  Polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of diabetic children  Prostaglandins, Leukotrienes and Essential Fatty Acids. 67(4); Oct 2002: 203-210

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

Brain Fog

red-bow-on-fingerThere is a relationship between central nervous system missteps and markers of inflammation. Age doesn’t matter; it happens across the board. If the occasional bout of forgetfulness strikes you, you might recoil in fear of early-onset dementia, especially if the “occasions” are too close together. Is there anything you can do about this? Could it be something you ate? Maybe it’s something you didn’t eat.

Inflammation is a protective response to injury or destruction of tissue that tries to rid the body of the detrimental agent. The process elevates blood markers that are useful in predicting the onset of chronic conditions, such as diabetes or cardiovascular disease. One of these markers is called homocysteine, an amino acid made from methionine that degrades arterial architecture.  But what of mental lapses?  “Epidemiological studies show a positive, dose-dependent relationship between mild-to-moderate increases in plasma total homocysteine concentrations (Hcy) and the risk of neurodegenerative diseases, such as…cognitive impairment…”  (Herrmann.  2011)  Cognitive impairment is not necessarily a sign of impending dementia or Alzheimer’s disease, but elevated homocysteine is “…a surrogate marker for B vitamin deficiency (folate, B12, B6) and a neurotoxic agent.”  (Ibid.)

If you can provide details about your forgetfulness, you don’t have dementia. If you can recall what you read yesterday about the local political scene, you don’t have dementia. If you forgot where you put the car keys, join the crowd.  Nonetheless, you could have homocysteine levels that are too high for your own good.  It’s recognized that taking classes, doing word puzzles, playing chess, and generally challenging the mind can preserve memory.  But these activities won’t necessarily influence renegade body chemistry. Though conjectural, it has been suggested that inflammation disrupts the integrity of the blood-brain barrier, the highly selective membrane that protects the brain from pathogens in the blood, as well as regulates which molecules can pass between the blood and the cerebral spinal fluid. Inflammation compromises the function of the membrane, allowing large molecules access to the brain, resulting in neuronal damage.  (Stolp. 2009).

Herrmann and Obeid (2011) admit that the prospect of improving any degree of neurological distortion caused by homocysteine can be realized with B vitamins. Parallel independent investigation revealed that women with cognitive abasement had higher Hcy values than women without such a burden, and that the folate (a B vitamin also called B9) levels of the affected cohort were measurably lower.  (Faux. 2011)

Homocysteine can be changed back to methionine under the right conditions, namely in the presence of a methylation molecule, such as folic acid (called folate in food). Folate insufficiency, or outright inadequacy, can initiate mental lapses that could balloon into more serious conditions if deficit is prolonged. Therapeutically, folic acid is able to reduce Hcy and the occurrence of neural tube defects in neonates. A side benefit was observed to be the prevention of cervical dysplasia and protection against neoplasm formation in ulcerative colitis.  (Kelly.  1998) Geriatric scientists had indicted homocysteine as causative of neurobehavioral anomalies across a wide range of cognitive domains (Jyme. 2005), and later identified vitamin B12, vitamin B6, and folate (or folic acid) as ameliorative agents.  (Selhub. 2010)

Homocysteine levels do not always increase because of something we did or ate, but because of something we didn’t eat. That would be the foods providing ample supplies of B12, B6, and folic acid.  Certain chronic and contagious diseases that evoke an inflammatory response, even the flu or seasonal allergies, can bring on a foggy mind. Relieving the cause should bring physical relief, and changing the body chemistry should eliminate the fog. All you need is a cue to help you remember that your sunglasses are sitting above your eyebrows.

References

Herrmann W, Obeid R.
Homocysteine: a biomarker in neurodegenerative diseases.
Clin Chem Lab Med. 2011 Mar;49(3):435-41.

Stolp HB, Dziegielewska KM.
Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases.
Neuropathol Appl Neurobiol. 2009 Apr;35(2):132-46.

Faux NG, Ellis KA, Porter L, Fowler CJ, Laws SM, Martins RN, Pertile KK, Rembach A, et al
Homocysteine, Vitamin B12, and Folic Acid Levels in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: Baseline Characteristics in Subjects of the Australian Imaging Biomarker Lifestyle Study.
J Alzheimers Dis. 2011 Sep 2.

Kelly GS
Folates: supplemental forms and therapeutic applications.
Altern Med Rev. 1998 Jun;3(3):208-20.

Jyme H. Schafer, MD, MPH; Thomas A. Glass, PhD; Karen I. Bolla, PhD; Margaret Mintz, MS; Anne E. Jedlicka, MS; Brian S. Schwartz, MD, MS
Homocysteine and Cognitive Function in a Population-based Study of Older Adults
J Am Geriatr Soc. 2005;53(3):381-388

Selhub J, Troen A, Rosenberg IH.
B vitamins and the aging brain.
Nutr Rev. 2010 Dec;68 Suppl 2:S112-8.

Schulz RJ.
Homocysteine as a biomarker for cognitive dysfunction in the elderly
Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):718-23.

Aron M. Troen, Melissa Shea-Budgell, Barbara Shukitt-Hale, Donald E. Smith, Jacob Selhub, and Irwin H. Rosenberg
B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice
PNAS August 26, 2008 vol. 105 no. 34 12474-12479

Roberts RO, Geda YE, Knopman DS, Boeve BF, Christianson TJ, Pankratz VS, Kullo IJ, Tangalos EG, Ivnik RJ, Petersen RC.
Association of C-reactive protein with mild cognitive impairment.
Alzheimers Dement. 2009 Sep;5(5):398-405.

Mancinella A, Mancinella M, Carpinteri G, Bellomo A, Fossati C, Gianturco V, Iori A, Ettorre E, Troisi G, Marigliano V.
Is there a relationship between high C-reactive protein (CRP) levels and dementia?
Arch Gerontol Geriatr. 2009;49 Suppl 1:185-94.

Herrmann W
Significance of hyperhomocysteinemia.
Clin Lab. 2006;52(7-8):367-74.

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

Allergy and Inflammation

allergiesIf you’re among the susceptible, the first whack in the face by a giant pollen ball is enough to set you back.  You get the runny nose, the watery eyes, the headaches and all the accessories.  If they were temporary symptoms, you wouldn’t pay much attention.  A handful of tissues and a couple of antihistamines, and you’re on your way.  Few of us understand, though, that seasonal allergies incite an inflammatory response, which is a protective attempt by the body to remove the enemy and clean up the place where it was.  Inflammation is not infection, but may be caused by it.  It’s considered part of the innate immune system, which activates as a function of your natural biological makeup.

Allergic disorders, which include hay fever, eczema and asthma, afflict almost a quarter of the population in the developed world (Holgate, 1999) (Galli, 2008).  Persistent exposure to allergens, basically innocuous substances in the environment, results in chronic allergic inflammation.  This can cause the affected organ(s) to go through substantial changes in function.  In fact, some people can develop a potentially fatal systemic reaction, called anaphylaxis, within seconds of exposure to an allergen (Simons, 2011).  Certain foods, as well as other non-infectious substances, may be involved.  In allergic responses, allergen-specific immunoglobulin E (IgE) and T helper cells (Th2) are switched on.

An acute response to an allergen that happens after a single exposure is called an early-phase reaction, or a Type-1 immediate hypersensitivity reaction.  Histamine is released here during mast cell degranulation. These molecules hook up with IgE and eventually cause itching, mucus production, swelling of blood vessels (vasodilation), edema and the airway constriction seen in allergic asthma (Hansen, 2004)  (Katelaris, 2003).  Chronic inflammation may be characterized by a continuum of tissue destruction and healing that may lead to loss of function, but this is not often seen with seasonal allergies, called allergic rhinitis. Allergic rhinitis is linked to decreased learning, poor performance at work and school, and of course, reduced quality of life.  The course of action taken by a doctor offers several pharmacologic options (Sadeq, 2004), many of which are shunned by patients in favor of natural alternatives.  Allergen-specific immunotherapy is designed to suppress the mechanism that responds to allergen attack.  This entails the use of chemical agents to regulate body function (Fujita, 2012), and this engenders a jaundiced eye among the holistic crowd.

Within the domain of complementary and alternative medicine is a plant whose use predates medieval times—stinging nettle, scientifically known as Urtica dioica.   For hundreds of years it’s been used to treat gout, painful joints, arthritis, eczema and anemia.  In modern times, nettle has been used to treat urinary problems during the early stages of benign prostate hyperplasia, and to treat urinary infections and hay fever.  It’s also been used in compresses to address joint pains, sprains and strains, tendinitis and insect bites.  Freeze-dried preparations were matched against placebo in a double-blinded randomized allergic rhinitis study performed at the National College of Naturopathic Medicine, and were found to be more effective than placebo at relieving symptoms (Mittman, 1990).  Cytokines are regulatory proteins that are released by cells of the immune system, where they act as mediators in the generation of an immune response, and may be assayed by the measurement of Th1 and Th2 cells, as well as by other markers of immune activation.  Extracts of stinging nettle, registered in Germany for therapy of rheumatic disease, were found to inhibit the inflammatory cascade identified by these artifacts (Klingelhoefer, 1999).

Quercetin is a bioflavonoid derived from red wine, citrus, onions, parsley, apples and tea, demonstrating several noble qualities, anti-inflammation and anti-oxidation among them.  The anti-inflammatory property arises from its inhibition of the production and activity of leukotrienes and pro-inflammatory prostaglandins, and inhibition of histamine release by basophils and mast cells.  Additionally, quercitin represses expression of the COX2 enzyme that is responsible for the manufacture of pro-inflammatory substances, and it stems the interleukins that characterize inflammation (Nieman, 2007).  Studies at Northwestern University agree that quercitin has its place as a primary therapy or as an adjunct in the treatment of allergic rhinitis (Thornhill, 2000).  Ocular symptoms of allergy are uncomfortable and often more bothersome than nasal symptoms.  Japanese scientists found that quercitin, in a double-blind placebo-controlled study, was substantially more effective than placebo at ameliorating the ocular symptoms that can plague sufferers of allergic rhinitis.  Ocular scores that rated tearing, itching and ocular congestion were low, while nasal scores differed little from the control group (Hirano, 2009).

Complementary medicine is not without allies in the allopathic medical community, especially when a supplement has proven efficacy against a traditional modality.  In the conventional medical sector, where raised eyebrows are the norm after the mention of complementary approaches, bromelain, the proteolytic enzyme from pineapple that digests proteins and tenderizes meat, has found favor in the treatment of otolaryngology disorders that include allergic rhinitis.  In a multicenter trial composed of 116 children, bromelain monotherapy (used by itself) effected faster recovery from sinusitis compared with standard therapy (Karkos, 2007).  As adjunctive to traditional therapy, bromelain exhibited supportive strength against acute rhinosinusitis (Guo, 2006).  Although marketed as a digestive aid, bromelain appears to have systemic anti-inflammatory activity (Hale, 2005) (Kumakura, 1988) (Onken, 2008).

In recent announcements, oral vitamin D added to regular intranasal corticosteroid dosing improves symptoms beyond that seen with corticosteroids alone, leading researchers to conclude that vitamin D affords benefit to patients with allergies (Baroody, 2012).  Treating inflammation may be nearer at hand than previously thought, and that just might eliminate, or at least reduce, the misery of seasonal allergy.

References

Ahmadiafshar A, Taghiloo D, Esmailzadeh A, Falakaflaki B.
Nasal eosinophilia as a marker for allergic rhinitis: A controlled study of 50 patients.
Ear Nose Throat J. 2012 Mar;91(3):122-4.

F. M. Baroody, J. Lane, S. Watanabe, M. DeTineo, J. Pinto, R. M. Naclerio;
The Addition of Vitamin D (VitD) to an Intranasal Steroid (INS) Improves Control of Symptoms in Seasonal Allergic Rhinitis (SAR)
J ALLERGY CLIN IMMUNOL.  FEBRUARY 2012;  abstract 510

G. Walter Canonica, MD
Treating Asthma as an Inflammatory Disease
CHEST July 2006 vol. 130 no. 1 suppl 21S-28S

Fujita H, Meyer N, Akdis M, Akdis CA.
Mechanisms of immune tolerance to allergens.
Chem Immunol Allergy. 2012;96:30-8.

Fujita H, Soyka MB, Akdis M, Akdis CA.
Mechanisms of allergen-specific immunotherapy.
Clin Transl Allergy. 2012 Jan 5;2(1):2

Stephen J. Galli, Mindy Tsai & Adrian M. Piliponsky
The development of allergic inflammation
Nature 454, 445-454 (24 July 2008)

Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S.
Quercetin Attenuates TNF-Induced Inflammation in Hepatic Cells by Inhibiting the NF-κB Pathway.
Nutr Cancer. 2012 Mar 27.

Guo R, Canter PH, Ernst E.
Herbal medicines for the treatment of rhinosinusitis: a systematic review.
Otolaryngol Head Neck Surg. 2006 Oct;135(4):496-506.

Hale LP, Greer PK, Trinh CT, Gottfried MR.
Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease.
Clin Immunol. 2005 Aug;116(2):135-42.

Hansen I, Klimek L, Mösges R, Hörmann K.
Mediators of inflammation in the early and the late phase of allergic rhinitis.
Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):159-63.

Hirano T, Kawai M, Arimitsu J, Ogawa M, Kuwahara Y, Hagihara K, Shima Y, Narazaki M, Ogata A, Koyanagi M, Kai T, Shimizu R, Moriwaki M, Suzuki Y, Ogino S, Kawase I, Tanaka T.
Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis.
Allergol Int. 2009 Sep;58(3):373-82. Epub 2009 May 25.

Holgate ST.
The epidemic of allergy and asthma.
Nature. 1999 Nov 25;402(6760 Suppl):B2-4.

Jaber R.
Respiratory and allergic diseases: from upper respiratory tract infections to asthma.
Prim Care. 2002 Jun;29(2):231-61.

Jutel M, Akdis CA.
T-cell regulatory mechanisms in specific immunotherapy.
Chem Immunol Allergy. 2008;94:158-77.

Karkos PD, Leong SC, Arya AK, Papouliakos SM, Apostolidou MT, Issing WJ.
‘Complementary ENT’: a systematic review of commonly used supplements.
J Laryngol Otol. 2007 Aug;121(8):779-82. Epub 2006 Nov 24.

Katelaris CH.
Ocular allergy: implications for the clinical immunologist.
Ann Allergy Asthma Immunol. 2003 Jun;90(6 Suppl 3):23-7.

Klingelhoefer S, Obertreis B, Quast S, Behnke B.
Antirheumatic effect of IDS 23, a stinging nettle leaf extract, on in vitro expression of T helper cytokines.
J Rheumatol. 1999 Dec;26(12):2517-22.

Kostyuk VA, Potapovich AI, Suhan TO, de Luca C, Korkina LG.
Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.
Eur J Pharmacol. 2011 May 11;658(2-3):248-56.

Kumakura S, Yamashita M, Tsurufuji S.
Effect of bromelain on kaolin-induced inflammation in rats.
Eur J Pharmacol. 1988 Jun 10;150(3):295-301.

Mittman P.
Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis.
Planta Med. 1990 Feb;56(1):44-7.

Nieman DC, Henson DA, Davis JM, Angela Murphy E, Jenkins DP, Gross SJ, Carmichael MD, Quindry JC, Dumke CL, Utter AC, McAnulty SR, McAnulty LS, Triplett NT, Mayer EP.
Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA.
J Appl Physiol. 2007 Nov;103(5):1728-35. Epub 2007 Aug 23.

Obertreis B, Giller K, Teucher T, Behnke B, Schmitz H.
Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid.
Arzneimittelforschung. 1996 Jan;46(1):52-6.

Jane E Onken, Paula K Greer, Brian Calingaert, Laura P Hale
Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro.
Clin Immunol. Volume 126, Issue 3, March 2008, Pages 345–352

Overman A, Chuang CC, McIntosh M.
Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media.
Int J Obes (Lond). 2011 Sep;35(9):1165-72.

Sadeq A. Quraishi, MHA;  Michael J. Davies, MD;  Timothy J. Craig, DO
Inflammatory Responses in Allergic Rhinitis: Traditional Approaches and Novel Treatment Strategies
J Am Osteopath Assoc May 1, 2004 vol. 104 no. 5 suppl 7S-15S

Simons FE.
Anaphylaxis pathogenesis and treatment.
Allergy. 2011 Jul;66 Suppl 95:31-4.

Skiepko R, Zietkowski Z, Tomasiak-Lozowska MM, Tomasiak M, Bodzenta-Lukaszyk A.
Bronchial hyperresponsiveness and airway inflammation in patients with seasonal allergic rhinitis.
J Investig Allergol Clin Immunol. 2011;21(7):532-9.

Thornhill SM, Kelly AM.
Natural treatment of perennial allergic rhinitis.
Altern Med Rev. 2000 Oct;5(5):448-54.

tYoon JS, Lee HJ, Choi SH, Chang EJ, Lee SY, Lee EJ.
Quercetin inhibits IL-1β-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves’ orbitopathy.
PLoS One. 2011;6(10):e26261.

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

Reduce Inflammation through Weight Loss

acute-pain-in-a-woman-kneeSome of us know inflammation too well. When getting out of bed in the morning becomes an auditory event in your joints that rivals a flamenco dancer’s castanets, you know inflammation. What you may not know, or at least not realize, is that your weight has something to do with it. For many of us, the seeds of inflammation were planted years ago. Our genes, body weight, diet, lifestyle and fitness determine our states of wellness and non-wellness, some of which we cannot sense. Silent inflammation is probably worse than that we can feel from getting cut or hit by a baseball. If it hurts or is uncomfortable, we’ll take care of it right away. If it’s not noticeable, it can smolder for years, eventually exploding into a chronic illness.

Inflammation is the response of tissue to injury or insult, occasionally caused by an invading pathogen. Characteristics, which you can sense, include increased blood flow to the injured area, elevated temperature, redness, swelling and pain. Inflammatory responses to what should have been a harmless agent include allergies and autoimmune diseases, states where the response is either out of proportion to the threat it faces or is directed against an inappropriate target, such as self. In these cases, the response is worse than anything the agent itself could have generated, and is often insensate. The cascade of cellular and molecular signals that accompany inflammation can perpetuate it and make it chronic, in which case monocytes and macrophages take over the management. This may sound cool, but the chemicals they create inside the tissues wreak havoc. Macrophages begin to swallow everything that appears derelict, including senescent cells and whatever is deemed a pathogen, whether it truly is or not.

At some point in this chronology, chemical mediators are released, including things like Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-a) and prostaglandins that keep the ball rolling…on and on. When the body tries to control all this nefarious activity it replaces damaged tissue with replacement cells of the same type, but occasionally fails and results in diseased states, such as asthma, rheumatoid arthritis, tendonitis, celiac and inflammatory bowel diseases.

Inflammation is recognized as causal to several chronic diseases and all-cause mortality, and is prevalent among those who have a body mass index above 30.0.  Biomarkers of inflammation are used to examine the relationship of inflammation to chronicity, with C-reactive protein (CRP), IL-6, TNF-a, and IL-8 as indicators. CRP probably is the first one your doctor will interpret, since it’s a prime marker of inflammation. It just doesn’t pinpoint the location. CRP is a native protein made by the liver in response to factors released by fat cells. In acute inflammation, such as from an infection, levels can rise in less than six hours and be hundreds of times higher than normal, which is lower than 10 mg per liter. With a severe bacterial infection, it can reach 200 or more. The absolutely perfect reading is 1.0. Levels above 2.4 are supposed to be associated with increased risk of cardiovascular events, but that’s debatable because the studies were done with people who had unstable angina (Pepys, 2003).

Human adipose tissue expresses and releases the pro-inflammatory artifacts, inducing low-grade systemic inflammation in people with too much body fat. Pediatricians in the Netherlands looked at overweight children in their country and saw higher levels of CRP than in normal-weight children (Visser, 2001), accompanied by higher white cell counts. In 2007, the Archives of Internal Medicine published an analysis of more than thirty separate studies, concluding that weight loss is a major factor in the reduction of CRP, adding that a loss of one kilogram (2.2 lbs) equates to a 0.13 mg/L drop in CRP (Selvin, 2007).

Many parents think that their kids will outgrow the chubby stage. Sometimes, yes; often, no. We now see 400-pound 20-year-olds who were obese at age eight, whose parents ignored admonitions to address the foreboded tragedy at the early age. That collection of fat that hangs over the belt, sometimes reaching the thighs, is called a panniculus, and is more than just a dormant spare tire. It secretes adipokines, or chemical signals, to other parts of the body, increasing risk of serious disease through disrupted homeostasis (Rosenow, 2010). If this describes someone you know, eventually you’ll likely see diabetes, heart disease, and maybe even some form of cancer (Ibid).

There are plenty of overweight seniors, some of whom achieve that senior designation at age 40, others above 70. Just by virtue of their age, they’re more likely to report joint pain, but obesity at any age is a predictor of low-grade chronic inflammatory state.  Whether by diet or exercise, or both, weight loss is extremely vital to maintaining one’s health. In comparisons, the low-carb folks lost more weight than the low-fat. Think about this.  The knee pain in the 50-year-old guy is so bad he can’t walk behind his lawnmower. The problem is that he’s carrying 375 pounds on a frame designed to carry 150-180, and his femur is squeezing the cushions at the tibia. Yes, it’s distinctly possible that thyroid issues are causative of the extra weight. There may be other factors that include lack of sleep, too much stress, certain medications, uncontrolled cortisol (kinda rare), and menopause in women. Some of these can be managed and can be worked out with the family physician and maybe a visit to a dietitian. However, looking more closely at his eating habits, we see carbohydrates as the main source of gustatory input, with beneficial fats and lean protein given the back seat. Self-inflicted obesity has no excuse. Inflammatory biomarkers can be attenuated with even a small reduction in weight (Miller, 2008) (You, 2006).  Now, get this. The physical movement required to mow the lawn might be just enough to reduce inflammation, despite the immediate discomfort, which will eventually taper off. (Ford, 2002) (Miller, 2008).

Obesity is a problem of epidemic proportions. Certain people are perceived as anathema, bête noir, pariah, and may pay for self-destructive behavior. If cigarette cessation clears the lungs, could weight reduction clear the blood? Yep. Dietary interventions will help both, but sticking a finger into the dike doesn’t quite do it.

References

Clément K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, Sicard A, Rome S, Benis A, Zucker JD, Vidal H, Laville M, Barsh GS, Basdevant A, Stich V, Cancello R, Langin D.
Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects.
FASEB J. 2004 Nov;18(14):1657-69.

Mary Elizabeth Dallas
Losing Weight May Lower Cardiac Risks
Study finds both low-carb and low-fat diets help overweight people reduce inflammation
NIH, 5 Nov, 2012
MedlinePlus Trusted Health Information for You A service of the U.S. National Library of Medicine
From the National Institutes of HealthNational Institutes of Health
http://www.nlm.nih.gov/medlineplus/news/fullstory_131011.html

Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D.
Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial.
JAMA. 2003 Apr 9;289(14):1799-804.

Ford, Earl S.
Does Exercise Reduce Inflammation? Physical Activity and C-Reactive Protein Among U.S. Adults
Epidemiology:. September 2002 – Volume 13 – Issue 5 – pp 561-568

Gilbert CA, Slingerland JM.
Cytokines, Obesity, and Cancer: New Insights on Mechanisms Linking Obesity to Cancer Risk and Progression.
Annu Rev Med. 2012 Oct 26. [Epub ahead of print]

Kawasaki N, Asada R, Saito A, Kanemoto S, Imaizumi K.
Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.
Sci Rep. 2012;2:799. Epub 2012 Nov 12.

Stephen P Messier, Claudine Legault, Shannon Mihalko, Gary D Miller, Richard F Loeser, Paul DeVita, Mary Lyles, Felix Eckstein, David J Hunter, Jeff D Williamson and Barbara J Nicklas
The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale
BMC Musculoskeletal Disorders 2009, 10:93

Miller GD, Nicklas BJ, Loeser RF.
Inflammatory biomarkers and physical function in older, obese adults with knee pain and self-reported osteoarthritis after intensive weight-loss therapy.
J Am Geriatr Soc. 2008 Apr;56(4):644-51. Epub 2008 Feb 28.

Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW.
Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.
J Clin Endocrinol Metab. 1997 Dec;82(12):4196-200.
Navarro SL, Brasky TM, Schwarz Y, Song X, Wang CY, Kristal AR, Kratz M, White E, Lampe JW.
Reliability of serum biomarkers of inflammation from repeated measures in healthy individuals.
Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1167-70. Epub 2012 May 7.

Nicklas BJ, Ambrosius W, Messier SP, Miller GD, Penninx BW, Loeser RF, Palla S, Bleecker E, Pahor M.
Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial.
Am J Clin Nutr. 2004 Apr;79(4):544-51.

Pepys MB, Hirschfield GM.
C-reactive protein: a critical update.
J Clin Invest. 2003 Jun;111(12):1805-12.

Anja Rosenow, Tabiwang N. Arrey, Freek G. Bouwman, Jean-Paul Noben, Martin Wabitsch, Edwin C.M. Mariman, Michael Karas, and Johan Renes
Identification of Novel Human Adipocyte Secreted Proteins by Using SGBS Cells
J. Proteome Res., 2010, 9 (10), pp 5389–5401

Roth CL, Kratz M, Ralston MM, Reinehr T.
Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children.
Metabolism. 2011 Apr;60(4):445-52. Epub 2010 May 24.

Elizabeth Selvin, PhD, MPH; Nina P. Paynter, MHS; Thomas P. Erlinger, MD, MPH
The Effect of Weight Loss on C-Reactive ProteinA Systematic Review
Arch Intern Med. 2007;167(1):31-39

Tam CS, Clément K, Baur LA, Tordjman J.
Obesity and low-grade inflammation: a paediatric perspective.
Obes Rev. 2010 Feb;11(2):118-26. Epub 2009 Oct 21.

André Tchernof, PhD; Amy Nolan, RD; Cynthia K. Sites, MD; Philip A. Ades, MD; Eric T. Poehlman, PhD
Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women
Circulation. 2002; 105: 564-569

You T, Nicklas BJ
Chronic inflammation: role of adipose tissue and modulation by weight loss.
Current Diabetes Reviews [2006, 2(1):29-37]

Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB.
Elevated C-reactive protein levels in overweight and obese adults.
JAMA. 1999 Dec 8;282(22):2131-5.

Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB.
Low-grade systemic inflammation in overweight children.
Pediatrics. 2001 Jan;107(1):E13.

Viviane Zorzanelli Rocha, M.D., Eduardo J. Folco, PhD, Galina Sukhova, PhD, Koichi Shimizu, M.D., Israel Gotsman, M.D., Ashley H. Vernon, M.D., and Peter Libby, M.D.
Interferon-gamma, a Th1 Cytokine, Regulates Fat Inflammation A Role for Adaptive Immunity in Obesity
Circ Res. 2008 August 29; 103(5): 467–476.

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

The Rumors on Rheumatoid Arthritis

hands-jarAunt Martha’s mother was the kindest, gentlest soul you’d ever meet. She went out of her way to make you feel at home. Food and drink were hallmarks of her cordial greeting. But she couldn’t open a package, twist open a jar or cut a cake. Her fingers were so badly gnarled that no two pointed in the same direction. Some of the joints formed the letter “Z.” Yet, despite the pain she must have borne, her loving smile prevailed. She was victimized by rheumatoid arthritis (RA) in an era when research was in its infancy, barely crawling.

This nefarious disease causes pain, swelling, stiffness and loss of function in joints— mostly hands and fingers, though it can strike any. It hits women more often than men, starting between ages twenty-five and fifty-five, though some statisticians start at forty. Unlike osteoarthritis, RA is an autoimmune condition that can affect body parts besides joints, such as the eyes, mouth and lungs. Nobody knows the cause. It could be genes, maybe the environment, or maybe hormones that direct the immune system to attack the body’s own tissues. Whatever it is, RA afflicts more than a million Americans, a sizeable fraction being kids.

The inflammation of RA can reach to the tendons, ligaments and muscles in some patients. Its chronic nature causes degradation of cartilage, bone and the ligaments that bind bones, causing deformity. Active disease presents with fatigue, appetite loss, low-grade fever, muscle and joint aches, and stiffness, the last being most notable in the morning or following periods of inactivity. Because RA is a systemic ordeal, its malevolence can inflame the glands around the eyes and mouth, causing Sjögren’s syndrome. RA-induced pleuritis is the inflammation of lung lining that causes pain with a deep breath. Because the number of red blood cells is reduced, anemia occurs, while a drop in white cells can be associated with an enlarged spleen and increased risk of infection.

Following examination of inflammatory blood markers and other criteria, the doctor can make a proper diagnosis, at which time medications probably will be prescribed. Cortisone and aspirin have been first-line drugs for decades because they act quickly. The slower ones are called disease-modifying anti-rheumatic drugs—DMARD’s—and include some heavy duty chemistry, not all of which is anti-inflammatory, but most of which has truly nasty side effects, many you have learned from television ads. What may not be realized is that some drugs destroy the substances your body needs to work the right way. The package insert that comes with the drug doesn’t tell you this, so you’ll think the absence of pain has all the bases covered. This is sufficient reason to visit an integrative dietitian or holistic-minded physician, the rare one who knows about nutrition.

Keeping your physician in the loop, you may opt to explore integrative measures to deal with RA. The good news is that there are recognized mediators of inflammation-induced bone damage (Nanjundaiah, 2013). Because of space constraints, we’ll address those with a pretty reliable track record, starting with gamma linolenic acid (GLA), an omega-6 fatty acid found in borage and evening primrose oils. While it is true that borage contains almost twice the levels of GLA as evening primrose, it is also true that borage contains pyrrolizidine alkaloids that can tax the liver. Though possibly in non-toxic amounts, these alkaloids are nonetheless there.  For that reason, EPO is often a preferred source of GLA. On the other hand, borage oil is used in clinical and observational studies because of its higher GLA values, thus requiring a smaller dosage (that may influence subject participation) and reducing cost. A University of PA study done in the early 90’s found that patients who took borage oil capsules for three months experienced reductions in pro-inflammatory prostaglandins and leukotrienes, leading to noticeable clinical improvement in RA symptoms (Pullman-Mooar, 1990).

Supplementing GLA at 3.0 and 6.0 grams a day enhances its conversion to the anti-inflammatory dihommo-gamma-linolenic-acid (DGLA), causing neutrophils to synthesize less pro-inflammatory leukotriene and platelet-activating factor (PAF—a major trigger of thrombosis), thereby attenuating discomfort (Johnson, 1997).  Compared to placebo in a six-month trial in Philadelphia, GLA was found to reduce the number of tender joints by more than a third and swollen joint count by more than a fourth, in a study from which no one withdrew (Leventhal, 1993).

Not to be outdone by its omega-6 counterpart, omega-3 fish oil flexed its anti-inflammatory muscle in trials that included non-steroidal anti-inflammatory drugs (NSAIDS) as part of the treatment. Swelling index and duration of early morning stiffness were used as markers for RA severity, and were found to have improved in subjective assessment by virtue of a decrease in pro-inflammatory leukotrienes (van der Tempel, 1990). Patients who received fish oil in combination with naproxen fared better in similar assessments than those without the fish oil or with placebo oil in studies carried out in Norway (Kjeldsen-Kragh, 1992) and New York (Kremer, 2000). A Canadian meta-analysis of seventeen n-3 studies concluded that morning stiffness and number of tender joints were reduced in those who used n-3 PUFA’s (Goldberg, 2007). Those who supplemented their OTC medications with omega-3’s from cod liver oil were able to reduce their dependence on NSAIDS (Galarraga, 2008).

In early reports, Danish scientists found that RA patients were deficient in the only mineral with anti-oxidant properties—selenium. They noted that those with the most active disease had the lowest values, and that there is significant correlation of selenium status with the number of affected joints (Tarp, 1985). Almost a decade later, the same researchers confirmed their initial findings, but also found that some subjects lack the physiological wherewithal to convert selenium to functional anti-oxidant enzymes, a state that can be overcome by supplemental mineral (Tarp, 1994).

From frankincense through ginger, to the resveratrol of grapes, science is takinga deliberate look at additions to the arsenal of RA treatments.

References

Astorga G, Cubillos A, Masson L, Silva JJ.
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Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, Ogston S, Nuki G, Belch JJ.
Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis.
Rheumatology (Oxford). 2008 May;47(5):665-9.

Goel, F. J. Ahmad, R. M. Singh, and G. N. Singh
3-Acetyl-11-keto-β-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity
Journal of Pharmacy and Pharmacology, vol. 62, no. 2, pp. 273–278, 2010.

Goldberg RJ, Katz J.
A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain.
Pain. 2007 May;129(1-2):210-23.

Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN, Chilton FH.
Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans.
J Nutr. 1997 Aug;127(8):1435-44.

Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R, Mikkelsen K, Førre O.
Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis.
J Rheumatol. 1992 Oct;19(10):1531-6.

Knekt P, Heliövaara M, Aho K, Alfthan G, Marniemi J, Aromaa A.
Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis.
Epidemiology. 2000 Jul;11(4):402-5.

Kremer JM.
n-3 fatty acid supplements in rheumatoid arthritis.
Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S.

Lau CS, Morley KD, Belch JJ.
Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis–a double-blind placebo controlled study.
Br J Rheumatol. 1993 Nov;32(11):982-9.

J. H. Lee, H. Jin, H. E. Shim, H. N. Kim, H. Ha, and Z. H. Lee
Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-κB signal
Molecular Pharmacology, vol. 77, no. 1, pp. 17–25, 2010.

M. Lei, S. Q. Liu, and Y. L. Liu
Resveratrol protects bone marrow mesenchymal stem cell derived chondrocytes cultured on chitosan-gelatin scaffolds from the inhibitory effect of interleukin-1β
Acta Pharmacologica Sinica, vol. 29, no. 11, pp. 1350–1356, 2008.

Leventhal LJ, Boyce EG, Zurier RB.
Treatment of rheumatoid arthritis with gammalinolenic acid.
Ann Intern Med. 1993 Nov 1;119(9):867-73.

S. A. Levy, O. Simon, J. Shelly, and M. Gardener
6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund’s adjuvant
BMC Pharmacology, vol. 6, article 12, 2006.

D. O. Moon, M. O. Kim, Y. H. Choi, Y. M. Park, and G. Y. Kim
Curcumin attenuates inflammatory response in IL-1β-induced human synovial fibroblasts and collagen-induced arthritis in mouse model
International Immunopharmacology, vol. 10, no. 5, pp. 605–610, 2010.

Morinobu, W. Biao, S. Tanaka et al.,
 (-)-Epigallocatechin-3-gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice
Arthritis and Rheumatism, vol. 58, no. 7, pp. 2012–2018, 2008.

Nanjundaiah SM, Astry B, Moudgil KD.
Mediators of inflammation-induced bone damage in arthritis and their control by herbal products.
Evid Based Complement Alternat Med. 2013;2013:518094.

Pullman-Mooar S, Laposata M, Lem D, Holman RT, Leventhal LJ, DeMarco D, Zurier RB.
Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid.
Arthritis Rheum. 1990 Oct;33(10):1526-33.

M. L. Sharma, S. Bani, and G. B. Singh
Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis
International Journal of Immunopharmacology, vol. 11, no. 6, pp. 647–652, 1989.

Tarp U, Overvad K, Hansen JC, Thorling EB.
Low selenium level in severe rheumatoid arthritis.
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Tarp U.
Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis.
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van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH.
Effects of fish oil supplementation in rheumatoid arthritis.
Ann Rheum Dis. 1990 Feb;49(2):76-80.

G. Xuzhu, M. Komai-Koma, B. P. Leung, et al.
Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B-cell function
Annals of the Rheumatic Diseases, vol. 71, no. 1, pp. 129–135, 2012.

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

Fructose Is an Inflammatory Word

corn-syrupInflammatory 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.

References

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.
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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.
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Seaman DR.
The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases?
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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.

What Gets YOU Inflamed?

knee-inflammationAre you an adult? Would you prefer the pound(s) of cure to the ounce of prevention? One of the sad commentaries about adulthood is that we don’t take care of ourselves until something hurts, the detection of which relies on the nervous system. The nervous system is plastic, meaning that it exhibits a wide range of responses according to different conditions. The perception of pain depends on more than one factor, the environment included. With inflammation, however, there exists a hypersensitivity state that makes us aware of what’s going on. This realization is called nociception, involving a network that identifies a noxious condition that evokes responses ranging from mild to severe. Once the pain message is recognized by the nervous system it registers as an “ouch.” The greater the intensity of the stimulus, the greater is the perception of pain. In some cases, no external trigger is needed, such as one would experience with arthritis pain.

Inflammation is the body’s attempt at self-protection, the intention of which is to remove the harmful stimuli, including damaged cells, irritants or pathogens. If the stimulus comes from outside, it can be removed, although pain may linger. If it comes from inside, the body is left to its own devices. In either instance, tissue repair is the ultimate goal. To our dismay, inflammation may beget further inflammation in a self-perpetuating cascade. This occurs because of cellular alterations that cause mediator chemicals to be released and certain white cells, called macrophages, to become activated. The job of the macrophage is to swallow (-phage) the debris that comes from, or causes, tissue damage. Without inflammation, infections and wounds would never heal. In fact, too much anti-inflammatory medication, such as cortisone, slows wound healing (Goforth, 1980). The innate immunity with which we were born is always at the ready to start the inflammatory cascade and to bring healing.

Signs of overt inflammation include pain, redness, immobility (as in loss of function), swelling, and heat (more blood to the area makes it feel warm). Covert inflammation, occurring with internal organs, does not necessarily present with all these signs. Pain arises when swelling pushes on nerves, but sometimes the brain gets used to it and ignores the stimulus. The risk for inflammatory conditions rises with weight gain, as determined by an increase in white blood cells. Regardless of body mass index, C-reactive protein and homocysteine are markers for the presence of inflammatory state, which is at the center of many disorders, from arthritis, through Crohn’s disease, to various allergies and vitamin deficiencies.

Treatment for inflammation abounds in the world of allopathic medicine. Most of us know about NSAIDS, non-steroidal anti-inflammatory drugs, among which Tylenol is not, but aspirin, naproxen and ibuprofen are. Then, there are the corticosteroids—or just plain steroids—that are naturally made by the body in the adrenal glands. But these guys, given as drugs, prevent phospholipid release, and that undermines the activity of eosinophils, which are designed to fight back against allergy, for example, by releasing histamine.

Of the alternative modalities to address inflammation, ginger has accrued quite a following. For hundreds of years it’s been used to treat gastric distress, including dyspepsia and constipation. Recent research points to ginger’s role as an anti-inflammatory agent in the prevention of colon cancer, where inflammation has been identified as a precursor to the disease (Zick, 2011), the markers of which are pro-inflammatory prostaglandins—primarily PGE2—produced by cyclooxygenase (COX) as an early event in the course of the condition (Jiang, 2012).

In a British examination of pain studies, those suffering from osteoarthritis, dysmenorrhea, and acute muscle pain had been administered ginger as the sole treatment. Though additional rigorous trials are anticipated, these subjects reported a reduction in pain, as cited on subjective assessment tools (Terry, 2011). Even before interest in alternative medicine was accelerated to its present status, scientists scrutinized ginger’s reputation in the Ayurvedic community among people treated with the herb for rheumatic concerns, finding efficacy that paralleled traditional interventions (Srivastava, 1989). Applying oral powdered ginger to generalized musculoskeletal discomfort, Danish physicians realized that the safety factor of ginger far exceeded that of any known drugs, while presenting significant efficacy in the relief of pain and swelling via the inhibition of pro-inflammatory prostaglandins (Srivastava, 1992).

By sequestering these incendiary prostaglandins (PG’s), ginger proves itself to be on a par with NSAIDS, minus the concerns of adverse side effects. Similar to prostaglandins in promoting physical aberrations are leukotrienes, products of an enzyme called lipoxygenase (LOX), like COX an offspring of arachidonic acid metabolism. Leukotrienes generally work within the immune system, while PG’s almost always play a role in pure inflammation and pain. (There are beneficent PG’s, by the way.)  Leukotrienes are signaling molecules that call immune cells to the site of infiltration, as from airborne allergens. Bluntly, ginger suppresses the synthesis of leukotrienes (Grzanna, 2005), a property that separates it from NSAIDS. Other of ginger’s attributes point to an anti-oxidant character in the interruption of free radical generation (Ali, 2008), which is helpful in the fight against allergens and pain.

Nitric Oxide (NO) is one of the few signaling gases in the body. The smooth muscle that lines blood vessels is told by NO to relax, thus dilating the vessels and lowering blood pressure. In excessive concentrations, though, NO becomes a pro-oxidant as a naturally unstable free radical, especially when made by white cells (monocytes and macrophages)  during their battle against an infective agent. One logistician that maintains regulation of NO is ginger, where it was shown to control white cell activation as part of its job as an anti-inflammatory vehicle (Shimoda, 2010). Modulating inflammation is what ginger does, and not so gingerly, at that.

References

Ali BH, Blunden G, Tanira MO, Nemmar A.
Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research.
Food Chem Toxicol. 2008 Feb;46(2):409-20. Epub 2007 Sep 18.

ltman RD, Marcussen KC.
Effects of a ginger extract on knee pain in patients with osteoarthritis.
A Arthritis Rheum. 2001 Nov;44(11):2531-8.

Drozdov VN, Kim VA, Tkachenko EV, Varvanina GG.
Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip.
J Altern Complement Med. 2012 Jun;18(6):583-8. doi: 10.1089/acm.2011.0202.

Frondoza CG, Sohrabi A, Polotsky A, Phan PV, Hungerford DS, Lindmark L.
An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures.
In Vitro Cell Dev Biol Anim. 2004 Mar-Apr;40(3-4):95-101.

Goforth P, Gudas CJ.
Effects of steroids on wound healing: a review of the literature.
J Foot Surg. 1980 Spring;19(1):22-8.

Grzanna R, Lindmark L, Frondoza CG
Ginger–an herbal medicinal product with broad anti-inflammatory actions.
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Seasonal Allergies – Autumn In New York

seasonal-allergiesAutumn in New York might be a great song, but that’s about as far as it goes for allergy sufferers. In a city made from concrete and glass, you’d think it was easy to escape an attack by natural allergens, like pollen and mold. Ragweed is the chief culprit that arouses immune cells to churn out antibodies to its pollen. The subsequent biochemical reactions flood the bloodstream with histamine, the chemical that gives rise to the familiar allergy symptoms. One ragweed plant can produce a billion grains of pollen in a season, and the grains are so light that they can travel hundreds of miles on the gentlest waft of air. That is why a city made of concrete and glass is not immune to a covert pollen attack. To make matters worse, you can’t just move to the mountains. The ragweed will follow you.

What used to be an allergy season running from mid-August to September is now on the calendar from the first of August to the middle of October. Rising temperatures and elevated carbon dioxide levels extend the season. Trees, grasses and molds are not dismissed as causes of seasonal misery. Damp leaves harbor molds that are kicked up when hit by the rake. In school, kids are assaulted by dust mites that have waited all summer for company.

It’s generally accepted that allergies are triggered by a protein. When a cruising lymphocyte identifies a threat it launches a countermeasure against it. In this complicated biochemical process antibodies are made. The particular antibody for allergic reactions is called immunoglobin E, or IgE, which attaches itself to mast cells and basophils, the cells that activate and release histamine. Histamine opens the flood gates of response, and blood vessels dilate, causing blood pressure to drop. The spaces surrounding cells fill with fluid and the symptoms begin—itching, hives, sneezing, wheezing, and more. In severe cases, anaphylactic shock may occur, a reaction that can be fatal if not handled immediately. The Epi-Pen addresses anaphylaxis. It contains epinephrine, a natural hormone that counteracts dangerous physiological changes that appear during allergic response.

Conventional treatments for allergies include steroid nasal sprays, antihistamines, decongestants, eye drops and shots. They’re used before, during and after symptoms occur. Rhinitis, characterized by irritated mucous membranes of the nose, is a common sign of seasonal allergy that responds to alternative measures, notably to butterbur. Butterbur rhizome extracts that are free of pyrrolizidine alkaloid hepatotoxic constituents have been found safe to use for up to four months (Schapowal, 2005), though many people use them longer. Pyrrolizidine alkaloids are produced by plants to protect them against insect herbivores, but are a danger to the liver, occluding small blood vessels and causing the organ to swell. Petasin, the active ingredient in butterbur, is an anti-inflammatory compound with relaxant properties (Ko, 2001), able also to inhibit histamine and leukotrienes, the latter being white blood cell components responsible for allergic and inflammatory reactions (Thomet, 2002).

Cetirizine is Zyrtec, the antihistamine that addresses the symptoms of allergic rhinitis. A quickened heartbeat, weakness or tremors, problems with urination, insomnia and dizziness are among its side effects. Butterbur, on the other hand, is generally well tolerated, although belching may occur, and those who are sensitive to some plant compounds may experience itching and mild rash. The fatigue and drowsiness common to cetirizine are absent. In a randomized study conducted in Switzerland, seasonal rhinitis patients receiving butterbur fared as well as those receiving cetirizine, without any of the sedative effects (Schapowal, 2002).

Nasal irrigation is the practice of using a fluid-filled vessel to flush excess mucus and debris from the nose and sinuses. Advocates insist that it promotes nasal and sinus health. The saline solution that is commonly employed may act as an antibacterial agent, as well. Being inexpensive and simple, the practice has gained considerable acceptance among Canadian and American medical practitioners, who agree that it could reduce reliance on antibiotics (Papsin, 2003) and antihistamines (Garavello, 2003). If it relieves symptoms, it’s a welcome ritual.

There is a plant chemical that acts simultaneously as a bronchodilator and an inhibitor of histamine and other allergic or pro-inflammatory chemicals in the body—quercetin, a compound common to apples, onions, dill, Hungarian peppers, capers and radishes. How’s that for diversity? Quercetin is a flavonoid, one of several substances known years ago as vitamin P, a designation that has fallen from favor. Flavonoids are noted for the coloration of many flowers designed to attract pollinators. In the higher plants, they act as chemical messengers, cell cycle inhibitors and directors of the total physiological machinery. Good for us is that these properties translate to humans, although they are slow to be recognized by the FDA and its European counterparts, primarily because absorption is an issue and clinical studies are few.

Where funding was available, outside the realm of pharmaceutical giants, quercetin and its comrades were found to demonstrate several pharmacological effects, including anti-viral, anti-microbial, anti-inflammatory and anti-allergic potential. These properties demonstrate a capability to down-regulate and to suppress certain of the many inflammatory pathways, including those involved in allergic inflammation and basophil enlistment (Chirumbolo, 2010). Of the flavonoids, quercetin is the most abundant, but has received the most attention because its effects on basophils are seen at billionth of mole concentrations, where studies in Italy learned that quercetin was able to sequester histamine release in activated cells (Chirumbolo, Marzotto, et al, 2010). Using mast cells sensitized with IgE, Japanese scientists learned that flavonoid varieties akin to quercetin display similar activity by inhibition of the calcium influx that signals the release of histamine and pro-inflammatory mediators (Kimata, 2000) (Kawai, 2007).

A regimen consisting of herbal interventions and dietary flavonoids (there are many to pick from) presents a complementary / alternative approach to the management of allergic misery with considerable effectiveness. Maybe it’s worth a try and you’ll save money on tissues.

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