Posts

OMEGA-3’S Effect On Aging

ageing-manHave you ever stopped to think there might be a difference between aging and getting old? Some ancient texts declare old age a virtue and a blessing, commanding the elderly to be respected for their wisdom, regardless of their scholarship. When your cheese gets old, it’s time to dump it; but when it ages, it reaches perfection, right?  When things get old, they might no longer be useful or in style. Aging is a managed process through which a thing gains value or desirability. Do we perceive ourselves the same way as cheese or steak? The way you live your life as you age just might dictate how others see you. Do you constantly complain about things outside your control, or do you roll with the punches and build on your strengths? You may balk at being reminded by your spouse to write things down. Make yourself look good; write them down. And try not to forget where you put the list.

Is there anything to be done to arrest the process of aging? There are scores of ads in magazines and on the web that proclaim the virtues of this or that herb or secret concoction to inhibit Mother Nature’s treacherous design. The only science that supports many of those claims is ringed by dollar bills. Really now, is there something, anything, that can take thirty years off my wrinkled brow, my flabby arms and other parts, my sagging skin, and shrinking self-concept? Instead of saying “No,” let’s take a look at science.

Inside the nucleus of a cell, our genes sit on double-twisted strands of molecules called chromosomes. At the ends of the chromosomes are protective caps called telomeres, which act just like the little plastic things at the end of your shoelaces (aglets) that keep them from raveling…or unraveling. Telomeres also keep the ends of the chromosomes from sticking to each other, which would not only make a big mess but could also scramble genetic information and cause diseases. But every time a cell divides, its telomeres shorten. After a while the telomeres get too short to duplicate and the cells kick out—they become old or they die. If enough of these die at the same time, so do we.

We’ll try not to get too complicated, but we need to explain that telomeres are sequences of DNA chemical codes that are made from the same stuff as the rest of the chromosomes and genes, called nucleic acid bases, that repeat. A neonatal telomere might have as many as eight thousand bases, about half that at middle age, and only fifteen hundred as an old timer. Each time a cell divides, we lose between 30 and 200 base pairs. Cells normally divide fewer than a hundred times before they die.  Now—pay attention here—there is an enzyme called telomerase that keeps the telomere from shrinking. Short telomeres set the stage for disease (Armanios, 2009) (Shen, 2007) (Serrano, 2004). Remember that. One thing science has yet to determine is whether telomeres start the aging process or are a sign that it has already begun. Still, the major cause of aging is believed to be oxidative stress, the state that results from simple things like breathing and from more complex activities that include infections, inflammation, smoking and booze, and the glycation that accompanies poor dietary choices (which is addressed in the AGE’s newsletter).

A very recent Ohio state study has discovered that omega-3 (n-3) fatty acids might slow aging. This work focused on overweight but healthy middle-aged and older adults who took n-3 supplements for four months and were later found to have altered the ratio of fatty acids in such a way as to preserve tiny segments of DNA in their white blood cells.  Guess what those tiny segments are…Yep, telomeres. Omega-3 supplementation also reduced signs of oxidative stress caused by excessive free radicals in the blood by almost fifteen percent compared to the controls (Kiecolt-Glaser, Sept 2012). The bottom line is that changing the omega-6 to omega-3 ratio from the common 15:1—up to 30:1 in some cases—to the tenable 4:1 is a prudent endeavor. However, don’t hurry to give the n-6’s short shrift. The American Heart Association announced in 2009 that a considerable body of research supports the use of omega-6 fatty acids as a means to reduce the incidence of coronary heart disease (Harris, 2009). Many of us have heard only negative things about omega-6 fats, never learning that they are precursors to many anti-inflammatory metabolites, including prostacyclins (vasodilators) and lipoxins (anti-inflammatory mediators). The findings of Harris and colleagues recommend that n-6 fatty acids make up 5% to 10% of daily energy intake. Given this, the 4:1 ratio of 6’s to 3’s is not so hard to handle (Simopoulos, 2002).

In a five-year study done at San Francisco General Hospital, patients with coronary heart disease, who also took omega-3 fatty acids as EPA and DHA, demonstrated prolonged survival by virtue of extended telomere length, in contrast to those whose telomeres were shortened by the absence or deficiency of omega-3 fatty acids (Farzaneh-Far, 2010). If maintaining telomere length is a positive step in deceleration of aging, we need to examine the elements that influence the opposite. Historical factors cannot be changed: genetics, early insults, prenatal conditions, and the like. But current factors can be altered and their results even reversed with behavioral interventions (Epel, 2012). One recommendation, then, is the faithful intake of n-3 fats, at least as a limiting agent for inflammation that relates to middle-aged torpid lifestyle and weight management (Kiecolt-Glaser, Aug 2010) and at most as an extender of telomere viability.

Telomeres maintain chromosome stability by repeating the sequence of the nucleic acid bases, TTAGGG on one strand of DNA bound to AATCCC on the other strand, where T is thymine, A is adenine, C is cytosine and G is guanine. In studies of human sisters with differing telomere lengths, investigators found that the women with shorter telomeres were at a moderately higher risk for breast cancer at premenopause than their siblings (Shen, 2007). Yes, short telomeres are acquired with aging, and yes, they need more study, and yes, they can mediate the degenerative effects of old age.

Inflammation is not a totally bad thing. Without it, wounds and infections wouldnot heal.  Pro-inflammatory chemicals start the attack against invaders,and then the real healing begins after the inflammation is shut off. The post-inflammatorysubstances clean up the dead and dying tissues and get rid of the inflammatorywaste products (Serhan, 2008) (Schwab, 2007) (Serhan, 2004). Those post-inflammatorymolecules—resolvins and protectins–are provided courtesy of n-3 fatty acids,and have proven themselves functional in telomere protection.

References

Adler N, Pantell M, O’Donovan A, Blackburn E, Cawthon R, Koster A, Opresko P, Newman A, Harris TB, Epel E.
Educational attainment and late life telomere length in the Health, Aging and Body Composition Study.
Brain Behav Immun. 2012 Sep 5. pii: S08810.1016/j.bbi.2012.08.014. [Epub ahead of print]

Armanios M, Alder JK, Parry EM, Karim B, Strong MA, Greider CW.
Short telomeres are sufficient to cause the degenerative defects associated with aging.
Am J Hum Genet. 2009 Dec;85(6):823-32.

Burghardt PR, Kemmerer ES, Buck BJ, Osetek AJ, Yan C, Koch LG, Britton SL, Evans SJ.
Dietary n-3:n-6 fatty acid ratios differentially influence hormonal signature in a rodent model of metabolic syndrome relative to healthy controls.
Nutr Metab (Lond). 2010 Jun 28;7:53.

Epel E.
How “reversible” is telomeric aging?
Cancer Prev Res (Phila). 2012 Oct;5(10):1163-8. doi: 10.1158/1940-6207.CAPR-12-0370.

Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA.
Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease.
JAMA. 2010 Jan 20;303(3):250-7.

Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F.
Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention.
Circulation. 2009 Feb 17;119(6):902-7. Epub 2009 Jan 26.

Kay-Tee Khaw, Marlin D. Friesen, Elio Riboli, Robert Luben, Nicholas Wareham
The EPIC-Norfolk Prospective Study
Plasma Phospholipid Fatty Acid Concentration and Incident Coronary Heart Disease in Men and Women:

Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Hwang BS, Glaser R.
Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial.
Brain Behav Immun. 2012 Aug;26(6):988-95. Epub 2012 May 26.

Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn E.
Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial.
Brain Behav Immun. 2012 Sep 23. pii: S0889-1591(12)00431-X. doi: 10.1016/j.bbi.2012.09.004.

Sanders TA, Lewis F, Slaughter S, Griffin BA, Griffin M, Davies I, Millward DJ, Cooper JA, Miller GJ.
Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP study.
Am J Clin Nutr. 2006 Sep;84(3):513-22.

Schwab JM, Chiang N, Arita M, Serhan CN.
Resolvin E1 and protectin D1 activate inflammation-resolution programmes.
Nature. 2007 Jun 14;447(7146):869-74.

Serhan CN, Chiang N.
Novel endogenous small molecules as the checkpoint controllers in inflammation and resolution: entrée for resoleomics.
Rheum Dis Clin North Am. 2004 Feb;30(1):69-95.

Serhan CN, Chiang N, Van Dyke TE.
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators.
Nat Rev Immunol. 2008 May;8(5):349-61.

Antonio L. Serrano, Vicente Andrés
Telomeres and Cardiovascular Disease:  Does Size Matter?
Circulation Research. 2004; 94: 575-584

Shen J, Terry MB, Gurvich I, Liao Y, Senie RT, Santella RM.
Short telomere length and breast cancer risk: a study in sister sets.
Cancer Res. 2007 Jun 1;67(11):5538-44.

Simopoulos AP.
The importance of the ratio of omega-6/omega-3 essential fatty acids.
Biomed Pharmacother. 2002 Oct;56(8):365-79.

Simopoulos AP.
Omega-3 fatty acids in inflammation and autoimmune diseases.
J Am Coll Nutr. 2002 Dec;21(6):495-505.

Xia SH, Wang J, Kang JX.
Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes.
Carcinogenesis. 2005 Apr;26(4):779-84. Epub 2005 Jan 20.

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

Fat Blocking Soda?

pepsi141112_insideNow we can eat all the fat we want in a meal and still lose weight. Forget that two cheeseburgers, fries and a soda, or fried onions rings/mushrooms and a juicy prime cut of beef with a gooey baked potato smothered in cheese sauce will render your blood as thick as petroleum jelly in a matter of minutes. The magic in this dining extravaganza is the soda, a new variety of cola that contains a fat blocker known as dextrin. But wait, first you have to travel to Japan to get this treat from Pepsi and its affiliate, Suntory, a company that distills booze “to bring happiness into the lives of our customers…in harmony with people and nature.” Yup, makes sense, eh?

Dextrin?
This is a group of carbohydrates that can be made by breaking down starch in the presence of water…hydrolysis. Dextrin also appears in the company of heat under acidic conditions, as happens to the crust on a loaf of bread, rendering flavor, color and crunch. Commercially, dextrins are used to make the glue on an envelope flap, the crispness enhancer in breaded frozen foods, and the cement that holds the pyrotechnics together in fireworks and sparklers. Because they are indigestible, dextrins are added to soluble fiber supplements, such as Benefiber. Whether they can help a person lose weight or not is another question; fiber’s claim to fame is increasing satiety and making you feel fuller faster. Fiber doesn’t actually push food through the system more quickly. Instead, it slows transit time through the stomach and small intestine, where digestion takes place. This is why fiber-rich foods keep you feeling full longer.  Once fiber gets to the large intestine, it keeps things in motion until they come out. It is true, though, that fiber can absorb some fat, but probably not enough to cause a significant weight loss in a short amount of time.

What About Fat?
Eliminating fat from the diet completely is not prudent. We need it to digest, absorb and transport vitamins A, D, E, and K, which are fat-soluble. The body demands the essential fatty acids, the omega-6’s and omega-3’s, to make substances that address inflammation, affect cell signaling, and add fluidity to the cell membrane. Furthermore, fat is an insulator and it provides a place for organs to attach while acting as a cushion, and it helps to keep the skin supple. If there is a problem with fat, it’s that one gram has 9 calories, contrasted to the 4 calories of carbohydrates and proteins. Fat gets broken down by enzymes, pancreatic lipase being the primary one. In the absence of this enzyme, fat molecules remain too large to be absorbed, so are excreted. The objective of the dextrins is to absorb some of this fat and usher it out the back door.

There are substances that do not absorb fats but prevent their breakdown, keeping their molecules too large to be metabolized so that they get eliminated quickly. One of the first of these was Orlistat, a prescription drug named Xenical that prevents the absorption of fat by inhibiting the enzymes that make the fat particles small enough to be metabolized.  But the side effects of drugs like this can be embarrassing, especially the urgent explosive diarrhea and gas, among a few other neat ones, like fainting or scratching yourself silly.  Alli is an over-the-counter version of Orlistat.

Does Dextrin Work?
According to the researchers at Japan’s NIH who studied this stuff, it works. The test animals were fed a high-cholesterol diet containing dextrin and a diglyceride, the latter molecule a fat used in foods to blend certain ingredients together, such as oil and water, which otherwise would not mix. Upon examination of the animals, the group found that serum triglycerides decreased and, strikingly, that the length of intestinal villi increased (Nagata, 2006).  Basically, less of the fat was absorbed. You can buy dextrin, either as Benefiber or Nutriose, and make your own soda or other high-fiber beverage (even one from Suntory).

What About The Vitamins?
Vitamin A, retinol, helps with night vision, bone growth, tooth development, reproduction, cell division and gene expression. It’s great for the skin and mucous membranes. It’s even recommended to treat acne. Vitamin D is needed to help the body to use calcium and phosphorus in the structure of bones. It supports the immune system and may help to prevent hypertension and common cancers. Vitamin E is an anti-oxidant that protects vitamins A and C, red blood cells and essential fatty acids from destruction via oxidative stress. Vitamin K is naturally produced by gut bacteria, but is also found in foods and as a supplement. It not only helps blood to clot normally, but also escorts calcium to bones where it can’t contribute to arterial plaque. There‘s more, but we don’t have the room for that right now. None of these can be utilized without fat in the diet, so if you choose to use dextrin to absorb fat from a meal, be deliberate, keep things in balance, and supplement.

References

Carter R, Mouralidarane A, Ray S, Soeda J, Oben J.
Recent advancements in drug treatment of obesity.
Clin Med. 2012 Oct;12(5):456-60.

Carvalho MA, Zecchin KG, Seguin F, Bastos DC, Agostini M, Rangel AL, Veiga SS, Raposo HF, Oliveira HC, Loda M, Coletta RD, Graner E.
Fatty acid synthase inhibition with Orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model.
Int J Cancer. 2008 Dec 1;123(11):2557-65.

Kimura Y, Nagata Y, Buddington RK.
Some dietary fibers increase elimination of orally administered polychlorinated biphenyls but not that of retinol in mice.
J Nutr. 2004 Jan;134(1):135-42.

Lefranc-Millot C, Guérin-Deremaux L, Wils D, Neut C, Miller LE, Saniez-Degrave MH.
Impact of a resistant dextrin on intestinal ecology: how altering the digestive ecosystem with NUTRIOSE®, a soluble fibre with prebiotic properties, may be beneficial for health.
J Int Med Res. 2012;40(1):211-24.

Nagata J, Saito M.
Effects of simultaneous intakes of indigestible dextrin and diacylglycerol on lipid profiles in rats fed cholesterol diets.
Nutrition. 2006 Apr;22(4):395-400. Epub 2006 Feb 2.

Sheikh-Taha M, Ghosn S, Zeitoun A.
Oral aphthous ulcers associated with orlistat.
Am J Health Syst Pharm. 2012 Sep 1;69(17):1462, 1464. doi: 10.2146/ajhp120073.

Seguin F, Carvalho MA, Bastos DC, Agostini M, Zecchin KG, Alvarez-Flores MP, Chudzinski-Tavassi AM, Coletta RD, Graner E.
The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16-F10 melanomas.
Br J Cancer. 2012 Sep 4;107(6):977-87. doi: 10.1038/bjc.2012.355. Epub 2012 Aug 14.

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

The Skinny On Skin

Summer beautyUnlike other organs of the body, skin nutrition can be enhanced by “direct deposit” through topical application of micronutrients, which can complement dietary acquisition and result in a stronger, healthier barrier to the world. Did you know that, when you look at a person, you are looking at dead skin? That would be the horny, keratinized outer layer called the stratum corneum. Keratin is a protein that helps to keep skin hydrated by preventing water evaporation. You might recognize it as the major component of wool, nails, rhino horns, and quill pens. The cells of the stratum corneum can also absorb water, which explains the puffiness and wrinkling you get in your fingers from sitting in the tub too long. Be glad this doesn’t happen all over. Sometimes, when your skin gets dry and itchy, you can see flakes of it when you scratch. That is the stratum corneum, part of the epidermis, which also contains the skin pigmentation chemical called melanin. Since people who look at you are seeing the walking dead, you might as well try to make it at least a little bit attractive.

Dry skin can be caused by harsh detergents and soaps, and by nutritional deficiencies, especially of essential fatty acids. Diet aside, at least for now, topical treatments can help to keep skin moist and pliable. There are no blood vessels in the epidermis to deliver nutrients to the stratum corneum, which usually prevents the passage of many types of molecules to layers below. Sometimes, though, a compound will pass through. Changes in temperature, air flow and humidity can pull water away from the skin and interrupt its integrity. If ignored, this can lead to more serious concerns, including cell damage and inflammation that perpetuate the condition. An important strategy is to address dry skin by maintaining the lipid components of what is termed the natural moisturizing factor.

The outer layers of the epidermis receive less nutritional support than underlying cells, hence the slowness and limitation of dietary interventions to offer positive effects. On the bright side, concentrations of nutrients in the skin can eventually be met through oral avenues. On the other hand, topical application may be more efficient, especially to ameliorate the ravages of photodamage (Pinell, 2003) (Zussman, 2010). Long before other insults were considered, poor nutrition was associated with changes in skin appearance, with the vitamin C deficit known as scurvy being among the first to be identified. Later associations, such as pellagra and ariboflavinosis, were found to be correctible through diet.

The topical use of micronutrients is a relatively new area of study (Boelsma, 2001). Much has been discussed and publicized about vitamins C, D, and E for skin health. Fatty acids have also been part of the conversation, and ceramides are slowly coming into the limelight (Coderch, 2003) (Guillou, 2011). This is warranted because the stratum corneum contains high levels of ceramides, constituting as much as half the total lipids, where they serve as a kind of glue that holds surface skin cells together.

But a not-so-new-kid on the block is gaining recognition for participation in the parade that leads to rescue of failing skin—the B-vitamins, 3 and 5. Nicotinamide (B3) is the amide of nicotinic acid, which is the form of niacin able to lower cholesterol and to cause flushing.  Nicotinamide is also called niacinamide, known to reduce glucose levels. Metabolically, nicotinamide is convertible to nicotinic acid. Though pharmacologically different, niacin/nicotinic acid and nicotinamide/niacinamide have the same vitamin activity. In a Japanese study conducted about a decade ago, it was found that topical nicotinamide is able to improve the permeability barrier of skin by stimulating the synthesis of ceramides, free fatty acids and cholesterol, with a subsequent decrease in transepidermal water loss (Tanno, 2000).

Not to be left out of the mix, panthenol likewise lends its magic to a topical lotion. Panthenol is the alcohol analog of pantothenic acid, also known as vitamin B5, that acts as a provitamin since it is quickly converted to vitamin B5. Only the D- form is biologically active, but both it and the L- form have moisturizing properties. In cosmetics, it may appear as DL-panthenol. Combined with niacinamide, this nutrient was shown to reduce a few obvious signs of aging skin, notably hyperpigmentation and redness. In a blinded study carried out in India, researchers found that subjects who applied such a lotion to the face daily for ten weeks experienced a significant reduction in redness and hyperpigmentation, an improvement in skin tone evenness, and positive effects on skin texture (Jerajani, 2010). Even in the absence of B5, the B3 application (niacinamide) alone was able to reduce the same negative features while simultaneously diminishing fine lines and wrinkles (Bissett, 2005) (Kawada, 2008).

Traditionally, vitamins have played the role of co-enzymes. You still need to eat food to give the vitamins something to work with. Several vitamins, however, assume the role of endocrine mimics. Biotin is one of these. Critical to carboxylation—replacing a hydrogen atom (H) with a carboxyl group (COOH), as in the oxidation of products that result from the decomposition of carbohydrates, fats and proteins—biotin also induces epidermal cell differentiation (Bolander, 2006), a process that helps to make new cells. This is especially noticeable in the health of fingernails and animals’ hooves, which become increasingly brittle and friable in the absence of biotin (Colombo, 1990) (Hochman, 1993).

We all know that exposure to the sun helps to make vitamin D. But we also know that too much exposure can cause the skin problems we’re trying to prevent or to rectify. The sun’s ultraviolet light is part of the invisible band of radiation. Most (~95%) of the UV that reaches the earth is the lower-frequency, longer-length UVA, sometimes called black light, that penetrates more deeply into the skin than UVB, but is less intense. UVA is the tanning ray that plays a major role in photoaging. UVB is responsible for sunburn and reddening, damaging the superficial layers of the epidermis. Both are culprits. Nicotinamide has been involved in cellular energy restoration after UV irradiation and is found to be immune protective, but riboflavin—vitamin B2—has similar virtue in that it is vital to cellular energy metabolism. Scientists who speculated that B2 could offer immune protection as well as B3 after insult by UV light were correct. Topical riboflavin protected against both wavebands (Diona, 2010) (Yoshikawa, 1999), and oral riboflavin can prevent dermatitis (Lo, 1984).

Taking a single B vitamin orally may have undesirable results; taking it as part of the entire complex, or adding it to the complex, is not a concern. Deficiency of B vitamins can be related to acne, cracked lips, dryness, wrinkles and an uneven complexion, among other dermatological (and metabolic) involvements. Avoiding these issues may be as easy as taking a supplement or finding a fortified lotion.

References

Bissett DL, Miyamoto K, Sun P, Li J, Berge CA.
Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin.
Int J Cosmet Sci. 2004 Oct;26(5):231-8. doi: 10.1111/j.1467-2494.2004.00228.x.

Bissett DL, Oblong JE, Berge CA.
Niacinamide: A B vitamin that improves aging facial skin appearance.
Dermatol Surg. 2005 Jul;31(7 Pt 2):860-5; discussion 865.

Boelsma E, Hendriks HF, Roza L.
Nutritional skin care: health effects of micronutrients and fatty acids.
Am J Clin Nutr. 2001 May;73(5):853-64.

Bolander FF.
Vitamins: not just for enzymes.
Curr Opin Investig Drugs. 2006 Oct;7(10):912-5.

Coderch L, López O, de la Maza A, Parra JL.
Ceramides and skin function.
Am J Clin Dermatol. 2003;4(2):107-29.

Colombo VE, Gerber F, Bronhofer M, Floersheim GL.
Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy.
J Am Acad Dermatol. 1990 Dec;23(6 Pt 1):1127-32.

Diona L. Damian, Yasmin J. Matthews, Gary M. Halliday
Topical riboflavin attenuates ultraviolet B- and ultraviolet A-induced immunosuppression in humans
Photodermatology, Photoimmunology, & Photomedicine. Apr 2010; 26(2): 66-69

Guillou S, Ghabri S, Jannot C, Gaillard E, Lamour I, Boisnic S.
The moisturizing effect of a wheat extract food supplement on women’s skin: a randomized, double-blind placebo-controlled trial.
Int J Cosmet Sci. 2011 Apr;33(2):138-43. doi: 10.1111/j.1468-2494.2010.00600.x.

Hochman LG, Scher RK, Meyerson MS.
Brittle nails: response to daily biotin supplementation.
Cutis. 1993 Apr;51(4):303-5.

Jerajani HR, Mizoguchi H, Li J, Whittenbarger DJ, Marmor MJ.
The effects of a daily facial lotion containing vitamins B3 and E and provitamin B5 on the facial skin of Indian women: a randomized, double-blind trial.
Indian J Dermatol Venereol Leprol. 2010 Jan-Feb;76(1):20-6. doi: 10.4103/0378-6323.58674.

Kawada A, Konishi N, Oiso N, Kawara S, Date A.
Evaluation of anti-wrinkle effects of a novel cosmetic containing niacinamide.
J Dermatol. 2008 Oct;35(10):637-42. doi: 10.1111/j.1346-8138.2008.00537.x.

Lacroix B, Didier E, Grenier JF.
Role of pantothenic and ascorbic acid in wound healing processes: in vitro study on fibroblasts.
Int J Vitam Nutr Res. 1988;58(4):407-13.

Lo CS.
Riboflavin status of adolescents in southern China. Average intake of riboflavin and clinical findings.
Med J Aust. 1984 Nov 10;141(10):635-7.

Mori K, Ando I, Kukita A.
Generalized hyperpigmentation of the skin due to vitamin B12 deficiency.
J Dermatol. 2001 May;28(5):282-5.

New D, Eaton P, Knable A, Callen JP.
The use of B vitamins for cutaneous ulcerations mimicking pyoderma gangrenosum in patients with MTHFR polymorphism.
Arch Dermatol. 2011 Apr;147(4):450-3. doi: 10.1001/archdermatol.2011.77.

Pinnell SR.
Cutaneous photodamage, oxidative stress, and topical antioxidant protection.
J Am Acad Dermatol. 2003 Jan;48(1):1-19; quiz 20-2.

Rajendran Kannan, MB BS MD and Matthew Joo Ming Ng, MB BS M Med Dip OccMed FCFPS
Cutaneous lesions and vitamin B12 deficiency
An often-forgotten link

Can Fam Physician. 2008 April; 54(4): 529–532.

Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S.
Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier.
Br J Dermatol. 2000 Sep;143(3):524-31.

Yoshikawa K.
Vitamin and dermatology
Nihon Rinsho. 1999 Oct;57(10):2385-9.

Zussman J, Ahdout J, Kim J.
Vitamins and photoaging: do scientific data support their use?
J Am Acad Dermatol. 2010 Sep;63(3):507-25.

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

Essential Fats Explained

fattyacid-sourceThe essential fatty acids (EFA’s) are just that—essential, meaning they have to come from the diet because the body can’t manufacture them. They might be used as fuel, but they are absolute components of the biological processes that make us work. Only two fatty acid families are vital to humans, omega-6’s and omega-3’s. It’s been shown that their ratio is more important than their volume. The parent fatty acid (FA) in the omega-6 (n-6) line is linoleic acid, abundant in many vegetable oils and ultimately responsible for the biosynthesis of arachidonic acid and related prostaglandins, which are compounds that regulate physiological activities. Alpha-linolenic acid (ALA) is the mother omega-3 (n-3) fatty acid, commonly extracted from seed oils such as flaxseed and hemp, but also found in walnuts. Nearly every aspect of human physiology is affected by essential fats, receptors for which are located in practically every cell.

The n-6 fatty acids have been denigrated in recent years because their excess has been linked to several metabolic upsets. Unbalanced diets are harmful to health, and the n-6’s that overpopulate processed foods and rancid supermarket oils have contributed to myriad health woes. What possibly started out as a 1 to 1 or 2 to 1 ratio of n-6 fatty acids to n-3 fatty acids in the human diet eons ago has become a physiological disaster of imbalance, where the ratio exceeds 10 to 1 in the typical Western diet, and may even approach 20 to 1, or worse, in personal food intake. All fatty acids go through a process of desaturation and elongation to become eminently bioactive compounds. The ultimate products of the process are beneficial to human health, especially if they are made step-by-step by the body and not forced upon it through manufactured meals, unnaturally finished meat products, stale/oxidized vegetable oils, and fossilized eggs, not to mention horrific snack foods. In a healthy body, linoleic acid is converted to gamma-linolenic acid (GLA), which becomes arachidonic acid, from which come the chemicals that control inflammation. After adulthood, the body’s ability to make those conversions is uncertain, so starting with GLA gives us a head start. However, mother linoleic acid is anti-inflammatory in its own right and even a marginal conversion to GLA has been held effective in the management of conditions as diverse as rheumatoid arthritis, eczema and ADD/ADHD.

The n-3 parent, ALA, also must come from diet because humans lack the enzymes necessary to convert it from other fats. But it’s the downstream omega-3’s that get the publicity:  EPA and DHA. Like the n-6’s, the conversion of ALA to EPA and later to DHA is an uncertain proposition in adulthood, which is why most adults use fish oil, a source of pre-made fatty acids. Even in the absence of the requisite conversion co-factors (vitamin B6, Mg, biotin, vitamin B3, vitamin C and Zn), ALA is anti-inflammatory and cardiac friendly (Pan, 2012) (Vedtofte, 2012), with recent scrutiny heralding its potential to inhibit progression of atherosclerosis (Bassett, 2011). The most readily available source of ALA is flaxseed, although chia, the newest kid on the block, is entering the marketplace.

Signs of fatty acid deficiency include a dry scaly rash, impoverished growth in youngsters, increased susceptibility to infections and poor wound healing, but are uncommon. The enzymes that convert the parent fatty acids act preferentially toward the n-3’s. By the time these enzymes deal with the omega-3 fats, some of the omega-6’s have been used for energy, hence the need to get more 6’s than 3’s, in a ratio of about 4 to 1, as evidenced by intensive research done in the 1990’s and early-mid 2000’s (Yahuda, 1993, 1996) (Simopoulos, 2002, 2008). But this ratio is based on the body’s own manufacture of the downstream fatty acids, GLA and arachidonic acid (ARA) along the n-6 line (the latter now included in products designed for infants to insure proper brain development) and EPA/DHA down the n-3 line. Deficiency of essential fatty acids sometimes strikes those suffering from cystic fibrosis or fat malabsorption issues. If patients receive total parenteral nutrition without the inclusion of EFA’s, deficit will appear in about a week or two.

The dry weight of the brain is about 80% lipids, the highest of any organ. The long-chain polyunsaturated fats, especially the n-6 and n-3, are crucial in modulating neural function. They occupy as much as 30% of the brain’s dry weight, making their influence on neural membrane dynamics profound. The shift away from EFA’s in the Western—typically American—diet parallels a rise in mental disorders. The need to address EFA supplementation is real and current, with the inclusion of omega-6 fats a necessity, since GLA, the downstream scion of linoleic acid, has held its own in mental health studies (Vaddadi, 2006). Together, the n-6’s and n-3’s cooperate in a number of cellular functions that affect membrane fluidity, allowing the passage of food and energy into the cell and wastes out. Arachidonic acid is a precursor to signaling molecules in the brain and is a key inflammatory intermediate, while EPA and DHA work to support the cardiovascular system, and the brain and retina.

It is arachidonic acid that supports membrane fluidity in the hippocampus, the part of the brain that directs memory, spatial relations and inhibition (Fukaya, 2007). It is arachidonic acid that protects the brain against oxidative stress and activates proteins in charge of the growth and repair of neurons (Darios, 2006). There is conjecture that ARA supplementation during the early stages of Alzheimer’s disease may slow its progress and stave off symptoms (Schaeffer, 2009). That’s a pretty good promise for something that’s been spurned…for lack of knowledge. Of the n-3’s, EPA may be effective in addressing depressive conditions and behavioral anomalies, besides being able to reduce inflammation (Brind, 2001) (Song, 2007). There had been some concern that EPA adversely affects clotting factors and fibrinogen concentrations, increasing the likelihood of bleeding. That is not so (Finnegan, 2003). It does, however, improve blood viscosity and red blood cell deformity, which allows red cells to adjust their shape to squeeze through narrow blood vessels, like capillaries. Downstream from EPA is DHA, a major fatty acid in sperm, brain phospholipids and the retina of the eye, and found to lower triglycerides. But its claim to fame is its rapid accrual in the developing brain during the third trimester of pregnancy and early postnatal period (Auestad, 2003) (Wainwright, 2000).

You can safely bet the farm that endogenous (made by the body itself) substances are more tightly regulated than exogenous. For example, the arachidonic acid your body makes from linoleic acid is more respectable than that from a haphazardly slaughtered steer, which may or may not be completely lifeless before the abattoir starts to dress it. In fear and pain, the animal releases a torrent of adrenal hormones throughout its flesh, confounding the integrity of its innate fatty acids. Endogenous fatty acids are, therefore, more wholesome.

How do we acquire the parent fatty acids?  You could buy oils that boast omega-6 and omega-3 fatty acid content from the supermarket, but it’s almost guaranteed that the balance will be too far out of whack to deliver a benefit, and the purity of the oils is possibly iffy. In fact, they might upset the apple cart. An overabundance of n-3’s can shut the immune system down for lack of guidance by the n-6 inflammation directors. On the other hand, BodyBio Balance Oil is a blend of organic, cold-pressed sunflower and flaxseed oils that are purposely geared to supply a 4 to 1 ratio of fatty acids that the body needs to initiate the cascade to longer chain fats that present vibrant physiological activity. Just the anti-inflammatory properties of the mother fatty acids, linoleic from sunflower and alpha-linolenic from flax, are enough to warrant using the oils to bolster the body’s well-being and to work out some metabolic kinks. Used to make salad dressings or to dress vegetables in place of butter, Balance Oil has the potential to set straight that which is awry, and the essential fatty acid metabolites can help to clear the brain fog on a hazy day. Cerebral lipids, especially the long-chain fatty acids, have significant direct and indirect activity on cerebral function. Not only do they affect the membranes, but also many are converted to neurally active substances. There is good evidence that mental challenges are related to EFA depletion, the supplementation of which can ameliorate the most defiant state of affairs.

References

Auestad N, Scott DT, Janowsky JS, Jacobsen C, Carroll RE, Montalto MB, Halter R, Qiu W, et al
Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age.
Pediatrics. 2003 Sep;112(3 Pt 1):e177-83.

Bassett CM, McCullough RS, Edel AL, Patenaude A, LaVallee RK, Pierce GN.
The α-linolenic acid content of flaxseed can prevent the atherogenic effects of dietary trans fat.
Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2220-6. doi: 10.1152/ajpheart.00958.2010. Epub 2011 Sep 30.

Caramia G.
The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy.
Minerva Pediatr. 2008 Apr;60(2):219-33.

Chang CS, Sun HL, Lii CK, Chen HW, Chen PY, Liu KL.
Gamma-Linolenic Acid Inhibits Inflammatory Responses by Regulating NF-kappaB and AP-1 Activation in Lipopolysaccharide-Induced RAW 264.7 Macrophages.
Inflammation. 2009 Oct 20.

Darios F, Davletov B.
Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3.
Nature. 2006 Apr 6;440(7085):813-7.

da Rocha CM, Kac G.
High dietary ratio of omega-6 to omega-3 polyunsaturated acids during pregnancy and prevalence of post-partum depression.
Matern Child Nutr. 2012 Jan;8(1):36-48. doi: 10.1111/j.1740-8709.2010.00256.x. Epub 2010 Jun 21.

Dupasquier CM, Dibrov E, Kneesh AL, Cheung PK, Lee KG, Alexander HK, Yeganeh BK, Moghadasian MH, Pierce GN.
Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions.
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2394-402. Epub 2007 Jul 6.

Fernandes FS, de Souza AS, do Carmo Md, Boaventura GT.
Maternal intake of flaxseed-based diet (Linum usitatissimum) on hippocampus fatty acid profile: implications for growth, locomotor activity and spatial memory.
Nutrition. 2011 Oct;27(10):1040-7.

Finnegan YE, Howarth D, Minihane AM, Kew S, Miller GJ, Calder PC, Williams CM.
Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans.
J Nutr. 2003 Jul;133(7):2210-3.

Fukaya T, Gondaira T, Kashiyae Y, Kotani S, Ishikura Y, Fujikawa S, Kiso Y, Sakakibara M.
Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats.
Neurobiol Aging. 2007 Aug;28(8):1179-86. Epub 2006 Jun 21.

C. Gómez Candela, L. M.ª Bermejo López and V. Loria Kohen
Importance of a balanced omega 6/omega 3 ratio for the maintenance of health.Nutritional recommendations
Nutr Hosp. 2011;26(2):323-329.

Ángeles Guinda, M. Carmen Dobarganes, M. Victoria Ruiz-Mendez, Manuel Mancha
Chemical and physical properties of a sunflower oil with high levels of oleic and palmitic acids
European Journal of Lipid Science and Technology. 105(3-4); Apr 2003: 130-137

BRIAN HALLAHAN, MRCPsych and MALCOLM R. GARLAND, MRCPsych
Essential fatty acids and mental health
The British Journal of Psychiatry (2005); 186: 275-277

William S. Harris, PhD, FAHA, Chair;  Dariush Mozaffarian, MD, DrPH, FAHA;  et al
Omega-6 Fatty Acids and Risk for Cardiovascular Disease
A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention
Circulation. 2009; 119: 902-907

Kakutani S, Ishikura Y, Tateishi N, Horikawa C, Tokuda H, Kontani M, Kawashima H, Sakakibara Y, Kiso Y, Shibata H, Morita I.
Supplementation of arachidonic acid-enriched oil increases arachidonic acid contents in plasma phospholipids, but does not increase their metabolites and clinical parameters in Japanese healthy elderly individuals: a randomized controlled study.
Lipids Health Dis. 2011 Dec 22;10:241.

Lands B.
Consequences of essential Fatty acids.
Nutrients. 2012 Sep;4(9):1338-57.

Eric L. LIEN, Kurt STEINER and John C. WALLINGFORD
The Proper Balance of Essential Fatty Acids for Life
Journal of Oleo Science. Vol. 50 (2001) , No. 5 399-405

Maekawa M, Takashima N, Matsumata M, Ikegami S, Kontani M, Hara Y, Kawashima H, Owada Y, Kiso Y, Yoshikawa T, Inokuchi K, Osumi N.
Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses.
PLoS One. 2009;4(4):e5085. doi: 10.1371/journal.pone.0005085. Epub 2009 Apr 8.

Osumi N.
Fatty acid signal, neurogenesis, and psychiatric disorders
Nihon Shinkei Seishin Yakurigaku Zasshi. 2010 Jun;30(3):141-8.

Pan A, Chen M, Chowdhury R, Wu JH, Sun Q, Campos H, Mozaffarian D, Hu FB.
α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis.
Am J Clin Nutr. 2012 Dec;96(6):1262-73. doi: 10.3945/ajcn.112.044040. Epub 2012 Oct 17.

Pawels EK, Volterrani D.
Fatty acid facts, Part I. Essential fatty acids as treatment for depression, or food for mood?
Drug News Perspect. 2008 Oct;21(8):446-51. doi: 10.1358/dnp.2008.21.8.1272136.

Peet M, Brind J, Ramchand CN, Shah S, Vankar GK.
Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.
Schizophr Res. 2001 Apr 30;49(3):243-51.

Sakayori N, Maekawa M, Numayama-Tsuruta K, Katura T, Moriya T, Osumi N.
Distinctive effects of arachidonic acid and docosahexaenoic acid on neural stem /progenitor cells.
Genes Cells. 2011 Jul;16(7):778-90. doi: 10.1111/j.1365-2443.2011.01527.x. Epub 2011 Jun 13.

Sanders TA, Rana SK.
Comparison of the metabolism of linoleic and linolenic acids in the fetal rat.
Ann Nutr Metab. 1987;31(6):349-53.

Schaeffer EL, Forlenza OV, Gattaz WF.
Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.
Psychopharmacology (Berl). 2009 Jan;202(1-3):37-51.

Simopoulos AP.
The importance of the ratio of omega-6/omega-3 essential fatty acids.
Biomed Pharmacother. 2002 Oct;56(8):365-79.

Artemis P. Simopoulos
The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases
Experimental Biology and Medicine  233:674-688 (2008)

Meharban Singh
Essential fatty acids, DHA and human brain
Indian Journal of Pediatrics. Volume 72, Number 3 / March, 2005: 239-242

Song C, Zhao S.
Omega-3 fatty acid eicosapentaenoic acid. A new treatment for psychiatric and neurodegenerative diseases: a review of clinical investigations.
Expert Opin Investig Drugs. 2007 Oct;16(10):1627-38.

Uauy R, Hoffman DR, Peirano P, Birch DG, Birch EE.
Essential fatty acids in visual and brain development.
Lipids. 2001 Sep;36(9):885-95.

Vaddadi K.
Essential fatty acids and mental illness.
Int Rev Psychiatry. 2006 Apr;18(2):81-4.

Vedtofte MS, Jakobsen MU, Lauritzen L, Heitmann BL
The role of essential fatty acids in the control of coronary heart disease.
Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):592-6.

Wainwright P.
Nutrition and behaviour: the role of n-3 fatty acids in cognitive function.
Br J Nutr. 2000 Apr;83(4):337-9.

Yehuda S, Carasso RL.
Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10345-9.

Yehuda S, Brandys Y, Blumenfeld A, Mostofsky DI.
Essential fatty acid preparation reduces cholesterol and fatty acids in rat cortex.
Int J Neurosci. 1996 Sep;86(3-4):249-56.

Yehuda S, Rabinovtz S, Carasso RL, Mostofsky DI.
Essential fatty acids preparation (SR-3) improves Alzheimer’s patients quality of life.
Int J Neurosci. 1996 Nov;87(3-4):141-9.

Yehuda S, Rabinovitz S, Mostofsky DI.
Essential fatty acids are mediators of brain biochemistry and cognitive functions
J Neurosci Res. 1999 Jun 15;56(6):565-70.

Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI.
The role of polyunsaturated fatty acids in restoring the aging neuronal membrane.
Neurobiol Aging. 2002 Sep-Oct;23(5):843-53.

Young G, Conquer J.
Omega-3 fatty acids and neuropsychiatric disorders.
Reprod Nutr Dev. 2005 Jan-Feb;45(1):1-28.

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

Gut Health, Body Health

stomachThe large intestine is seldom the topic of conversation, with the possible exception of surgeons and gastroenterologists. Most “civilians” don’t pay attention to it until it isn’t working right. The inability to move material out of it is one reason. Unusual egesta might be another. Regardless of its laid back persona, the colon is actually an interesting character. It runs from the cecum (the beginning of the large intestine, where the appendix hangs) to the rectum (the dumpster), and extends about five or six feet. If you want to be technical, the colon runs between these two points. The large intestine has no digestive function, but lubricates wastes and absorbs water and remaining salts, and stores useless stuff for eventual removal. It takes about sixteen hours to evacuate the hold. You need to know that the large intestine absorbs vitamins made by colonic bacteria, such as vitamin K and the vitamin A converted from beta-carotene.

Despite that the colon is known for removal of material, there exists inside a raft of bacteria that keep a permanent residence. In fact, there are more bacteria in the colon than cells in the body. If you have ten trillion cells in your body, you have ten times that many microbes, weighing from two to five pounds. This microflora is sometimes called the microbiome or microbiota. Whichever term is used, the activities performed by these bacteria parallel that of an organ, rivaling the metabolic capacity of the liver (MacFarlane, 2010). For example, carbohydrates are fermented to form short-chain fatty acids that support epithelial cell growth, which helps to reduce the absorption of toxic products. The flora recycle carbon and nitrogen, manufacture methane, metabolize steroids, convert lignans and phytoestrogens to other compounds and fight invasion by unwelcome species. Although people can survive without them, these bacteria are among the best of friends. Damaged or abnormal gut flora is the cause of much human agony as a prime factor in disease. Treating the microbiome with dignity and respect may prevent, or even reverse, disorders that include heart disease, autoimmune conditions, allergies and cancer (deVrese, 2008) (Garcovich, 2012).

There are hundreds of different species of micro-organisms living in the gut, more than 95% of which are anaerobic and genetically diverse. A lactobacillus is more different from a bifidobacterium than a human is from a rabbit. Identification of all species is difficult because not all can be cultured, but you can rest assured that your bacteria belong to you, remaining fairly constant throughout your life time. Talk about close friends!  The healthy bacteria provide a natural barrier against pathogenic bacteria, parasites, fungi, viruses, toxins and whatever else would wreak havoc with our health. Basically, there are half a dozen main groups:  Bacteroides, Firmicutes (Clostridia, Lactobacilli, Streptococci), Actinobacteria (Bifido-), Proteobacteria (Entero-), Fusobacteria and Verrucomicrobia. Not all of these offer salubrity. Some are so complex they almost defy taxonomy, but to our benefit, the good control the evil (Vedantam, 2003) (Beaugerie, 2004).

Analyses have determined that specific gut microbes are associated with what we eat. Some are associated with carbohydrates and some with animal proteins, fats and amino acids. It appears they come to the front of the class when it’s their turn to perform. Changing diet from one type of macro-nutrient to another can alter which bacterial strain is on stage at the time. A baby’s gut is clean and sterile until it entertains bacteria from its mother. Vaginal birth may afford bacterial strains directly from mom’s gastrointestinal tract, while caesarean might present strains from the ambient environs, including the air and the attending medical folks. The infant doesn’t establish his own microbiota for up to six months after caesarean delivery, only one month for normal birth. In any case, the microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota (Nicholson, 2012).

The influence of gut microbes on immunity is profound and, therefore, associated with long-term health, particularly since microflora is relatively stable throughout adulthood. The dynamics of the gut environment are subject to perturbations, though, such as from stresses or dietary changes. It’s comforting to know that there is considerable interest in developing modalities that can manipulate biome composition to benefit the host through a kind of metabolic communication, such as would affect obesity and type 2 diabetes (Kootte, 2012). In these matters, therapeutic pathways may be designed by enlisting short-chain fatty acids, prebiotics, bile acids and probiotics. Realizing that antibiotics are non-selective in destroying bacteria—they kill the good as well as the bad—this give us the means for resolution of myriad complaints. In general, the host immune system can prevent the overgrowth of pathogens, which, upon ingestion, fall to this complex integrated structure.

Probiotics are helpful in many cases, but are not silver bullets. When used as part of a broad nutritional protocol, they are likely effective in establishing or re-establishing a healthy microbiome. Stress management, elimination of detrimental medications and dietary interventions need to be included in such a protocol. Because they are many and varied in their composition, probiotics are often viewed tentatively until they are administered and monitored for efficacy. Eating fermented foods, like sauerkraut, yogurt and kefir, fosters a nurturing environment for your own microbiome. The florae best known are the Lactobacilli (there are more than 50 strains) and Bifidobacteria (there are more than thirty). Lacto-, in one strain or another, have been used to treat and to prevent a variety of conditions, from bacterial vaginosis to childhood abdominal distress and diarrhea, to childhood respiratory infections. Bifidobacteria comprise about 90% of the intestinal community, and appear in an infant’s gut within days of parturition, especially if breastfed. The Bifido- species has been used to address irritable bowel syndrome, dental caries, blood lipids and glucose tolerance.  A knowledgeable nutrition professional can guide you in the choice of probiotics to meet a specific need if you have one. Oh, yeah, there is a yeast probiotic, called Saccharomyces boulardii, which is quite effective in treating diarrhea associated with antibiotic use, and may even be helpful with Clostridium difficile and acne.

Hey, what about short-chain fatty acids (SCFA), especially butyrate?  We’re glad you asked. Butyrate is derived from the bacterial fermentation of resistant starches and fibers. Its multiple beneficial effects have been demonstrated beyond the colon, mostly because SCFA can be absorbed across the colonic epithelium. Now that gut health has its own fan club, what with renewed interest in the GI barrier defense system, SCFAs are the darlings of moneyed research. These 2-carbons to 5-carbons fatty acids include acetate, propionate, butyrate and valerate, but the 4-carbon butyrate is the featured performer due to its multiplicity of virtues. Among butyrate’s mechanisms of action are the regulation of gene expression, inhibition of histone deacetylase (an action which helps to make copies of DNA), sequestration of ammonia (ammonia causes cloudy thinking), mobilization of renegade fats, and clearance of biotoxins (Soret, 2010) (Fusunyan, 1999) (Yin, 2001). Because butyrate availability in the colon is lower than the other SCFAs, supplementation is highly recommended. You can’t eat enough resistant starches to make enough butyrate to be physiologically significant. However, even at low concentrations, butyrate can inhibit cell proliferation of several colon cancer lines. At high concentrations, it works like gangbusters against cancer cells while leaving healthy cells alone (Omaida, 1996) (Gamet, 1992).

The extraordinary complexity of the human microbiome is only recently revealed, despite having been known for decades. The interdependence between beneficial bacteria and the immune system demands recognition. If the florae can fight the inflammation that threatens them, they can fight whatever threatens their host.

References

Arora T, Sharma R, Frost G.
Propionate. Anti-obesity and satiety enhancing factor?
Appetite. 2011 Apr;56(2):511-5. doi: 10.1016/j.appet.2011.01.016. Epub 2011 Jan 19.

Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB.
Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications.
Cell Host Microbe. 2012 Nov 15;12(5):611-22.

Beaugerie L, Petit JC.
Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea.
Best Pract Res Clin Gastroenterol. 2004 Apr;18(2):337-52.

Bischoff SC.
‘Gut health’: a new objective in medicine?
BMC Med. 2011 Mar 14;9:24.

Calder PC, Krauss-Etschmann S, de Jong EC, Dupont C, Frick JS, Frokiaer H, Heinrich J, Garn H, et al
Early nutrition and immunity – progress and perspectives.
Br J Nutr. 2006 Oct;96(4):774-90.

Roberto Berni Canani, Margherita Di Costanzo, and Ludovica Leone
The epigenetic effects of butyrate: potential therapeutic implications for clinical practice
Clin Epigenetics. 2012; 4(1): 4.

Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, et al
PASSCLAIM–gut health and immunity.
Eur J Nutr. 2004 Jun;43 Suppl 2:II118-II173.

de Vrese M, Schrezenmeir J.
Probiotics, prebiotics, and synbiotics.
Adv Biochem Eng Biotechnol. 2008;111:1-66. doi: 10.1007/10_2008_097.

Fanaro S, Chierici R, Guerrini P, Vigi V.
Intestinal microflora in early infancy: composition and development
Acta Paediatr Suppl. 441: 48-55. 2003

Flint HJ, Scott KP, Louis P, Duncan SH.
The role of the gut microbiota in nutrition and health.
Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):577-89.

Fusunyan RD, Quinn JJ, Fujimoto M, MacDermott RP, Sanderson IR.
Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.
Mol Med. 1999 Sep;5(9):631-40.

Gamet L, Daviaud D, Denis-Pouxviel C, Remesy C, Murat JC.
Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29.
Int J Cancer. 1992 Sep 9;52(2):286-9.

Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A.
Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota.
World J Gastroenterol. 2012 Dec 14;18(46):6693-700. doi: 10.3748/wjg.v18.i46.6693.

Guarner F, Malagelada JR.
Gut flora in health and disease.
Lancet. 2003 Feb 8;361(9356):512-9.

Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, et al
The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.
Diabetes Obes Metab. 2012 Feb;14(2):112-20.

Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ
Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.
PLoS One. 2012;7(4):e35240. doi: 10.1371/journal.pone.0035240. Epub 2012 Apr 10.

Macfarlane S, Macfarlane GT.
Regulation of short-chain fatty acid production.
Proc Nutr Soc. 2003 Feb;62(1):67-72.

MacFarlane, George T. and McBain, Andrew J. (2010). The Human Colonic Microbiota. In Colonic Microbiota, Nutrition and Health. Glenn Gibson, Ed. Dordrecht, the Netherlands: Kluwer Academic Publishers; pp 1-25

Martin FP, Dumas ME, Wang Y, Legido-Quigley C, Yap IK, Tang H, Zirah S, Murphy GM, et al
A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
Mol Syst Biol. 2007;3:112.

Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, et al
Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.
Mol Syst Biol. 2008;4:157.

Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S.
Host-gut microbiota metabolic interactions.
Science. 2012 Jun 8;336(6086):1262-7.

O’Hara AM, Shanahan F.
The gut flora as a forgotten organ.
EMBO Rep. 2006 Jul;7(7):688-93.

Omaida C. Velázquez MD, Howard M. Lederer MD, Dr. John L. Rombeau MD
Butyrate and the colonocyte
Digestive Diseases and Sciences. April 1996, Volume 41, Issue 4, pp 727-739

Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, et al
Prebiotic effects: metabolic and health benefits.
Br J Nutr. 2010 Aug;104 Suppl 2:S1-63.

Schwiertz A, Gruhl B, Löbnitz M, Michel P, Radke M, Blaut M.
Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants.
Pediatr Res. 2003 Sep;54(3):393-9. Epub 2003 Jun 4.

Scott KP, Duncan SH, Louis P, Flint HJ.
Nutritional influences on the gut microbiota and the consequences for gastrointestinal health.
Biochem Soc Trans. 2011 Aug;39(4):1073-8.

Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH.
The influence of diet on the gut microbiota.
Pharmacol Res. 2012 Nov 9. pii: S1043-6618(12)00207-1.

Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, Neunlist M.
Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.
Gastroenterology. 2010 May;138(5):1772-82.

Tsai F, Coyle WJ.
The microbiome and obesity: is obesity linked to our gut flora?
Curr Gastroenterol Rep. 2009 Aug;11(4):307-13.

Vedantam G, Hecht DW.
Antibiotics and anaerobes of gut origin.
Curr Opin Microbiol. 2003 Oct;6(5):457-61.

Yin L, Laevsky G, Giardina C.
Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity.
J Biol Chem. 2001 Nov 30;276(48):44641-6. Epub 2001 Sep 25.

Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S.
Destructive effects of butyrate on the cell envelope of Helicobacter pylori.
J Med Microbiol. 2012 Apr;61(Pt 4):582-9.

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

Diabetes Management: Dietary Interventions

diabetes-mangmntDiabetes, the word, is loosely derived from a Greek translation of “one that straddles,” probably referring to a person who urinates frequently. You already know this is considered a metabolic disease of several types, marked by frequent urine discharge, persistent thirst, and the inability to process sugars in the diet due to a decrease in, or absence of, insulin production. There also may be target tissue insulin resistance. Type 1 diabetes mellitus is one of the two major types. Here, the symptoms arise abruptly, often in early adolescence, and the person relies on exogenous insulin to sustain life. Onset may occur at any age, though. Among other miseries, type 1 affects blood vessel health (especially the tiny ones), and manifests in the retina, kidneys, and the underlying connective layer of arterioles. Type 2 diabetes often strikes between ages thirty and forty, with gradual onset that shows few symptoms of metabolic disturbance, at least not right away. With good fortune and careful management, there may be no need for exogenous insulin; diet and perhaps oral hypoglycemic medications can do the trick. Insulin response in type 2 is delayed or reduced, but insulin secretion is not necessarily absent. In this disorder blood vessels of various sizes are affected, particularly the large ones. This can lead to premature atherosclerosis, sometimes followed by myocardial infarction and stroke. Neither of these types of diabetes is to be taken lightly. There is also a third type of diabetes, diabetes insipidus, usually caused by hormone or kidney anomalies.

You might have heard people refer to themselves as having “a touch of diabetes.”  That’s the equivalent of being a little bit pregnant. Either you are, or you aren’t. Maybe you’ll hear folks say their sugar is “a little high.”  Either expression hints that diabetes is not a serious matter. That is wrong. Managing diabetes may not be the easiest thing in the world, but it certainly is achievable, and in the long run it’s well worth the effort. When your blood sugar is normal, you feel better—you have more energy, are less tired and thirsty, have fewer skin or bladder infections, you heal faster, and you have fewer problems with your vision, teeth and feet. Taking care of yourself will avoid heart attack and stroke, the possibility of blindness, nerve damage that causes tingling and numbness in hands and feet, kidney disease that may kill you, and gum disease that causes tooth loss. Hmm, this is serious business.

Unfortunately, the body is not modular in that an organ can be removed and replaced when the warranty is near expiration. It’s not like rotating tires. Even artificial joints don’t come with grease fittings. We have to make parts last as long as possible, despite that some can be replaced…an uncomfortable though to many of us. Prevention is still the best cure. Diabetes can lead to cardiovascular damage. Yes, eyesight and nerves can be damaged, too, but space restricts us to one topic at a time. Changes in the body don’t necessarily happen independently. The cycle of progressive vascular damage from diabetes affects the heart. Changing how we eat can manage glucose levels and prevent heart disease.  One dietary technique follows the glycemic index (GI), which is a measure of how fast blood sugar rises in response to a certain food.  The index estimates how much a gram of carbohydrate elevates blood sugar after consumption, relative to consumption of pure glucose, which is given an index value of 100. Subjects with diabetes managed only by a diet focusing on optimal glycemic control were found to have reduced postprandial glucose levels, accompanied by lower markers of inflammation, notably C-reactive protein (CRP), and improved lipid panels (Wolever, 2008). From time to time, meta-analyses are employed to examine relationships among disease-causing variables. Scrutinizing the GI relationship to CVD, Australian scientists, whose colleagues are credited with designing the GI, discovered a reduction in the risk for cardiovascular disease among diabetes patients who complied with the low GI regimen (Barclay, 2008). The low GI has such potential in the management of chronic disease that those who are morbidly obese may find heart-healthy value in following the plan (Ebbeling, 2005). Even in cases where diabetes is poorly controlled, adhering to the low GI diet has merit when combined with reduced carbohydrate intake in modulating CVD risk factors, including glycated hemoglobin, called HbA1c ( Afaghi, 2012) (Eskesen, 2013) (Zhang, 2012).  Glycated hemoglobin is formed through a non-enzyme pathway when hemoglobin is exposed to high plasma levels of glucose. Glycation forms end products that cause extreme oxidative stress on the body, affecting nearly every cell and molecule. The advanced glycation end products, termed AGE’s, increase vascular permeability, inhibit vascular dilation (and elevate blood pressure), interfere with nitric oxide production (which allows blood vessels to dilate), oxidize LDL, and excite excretion of cytokines. These pathological states invite cardiac entanglement, but can be managed successfully through dietary modification.

The Mediterranean Diet has been touted for its cardiovascular benefits, but little attention has been paid to its effect on diabetes issues.  This diet is a relative newcomer to us, although it’s been a way of life in the Mediterranean for years, generally in the less opulent areas of southern Italy, parts of Greece and a few islands. Despite being called such, this diet is not typical of the entire area. For instance, wine is avoided by the Muslims of the region, and butter, lard and other animal fats comprise part of the cuisine of various indigenous groups. One thing that is easily identifiable about this regional lifestyle is ambulation—everybody walks everywhere. You know very well that accounts for a lot. The diet is abundant in plant foods. Fruit is dessert, as opposed to the sugary stuff Americans eat. The main fat is olive oil; cheese and yogurt are the chief dairy products; red meat is more an accoutrement than a feature. Legumes, unrefined non-GMO cereals, huge amounts of fruits and vegetables, moderate consumption of fish and poultry, and little saturated fat are the norm.

A cohort of more than thirteen thousand Spanish university graduates was followed for four years to assess an association of diet and diabetes. Participants who followed the Mediterranean protocol had a lower risk of disease (Martinez-Gonzalez, 2008) (Dominguez, 2012). There was no beating about the bush in this report. The conclusion was stated with conviction. At the same time, it was noted that seduction by the typical Western diet of fast and prepared foods leads to increases in cardiovascular and metabolic complications (Tarabusi, 2010).

In all the controlled trials reviewed in recent years, those that featured low GI, low carbohydrate and Mediterranean diets all led to greater improvement in glycemic control, with the Mediterranean having the most profound influence on both glucose control and weight loss, enhanced by increases in HDL (Ajala, 2013). Reduction in markers of inflammation and decreases in AGE’s are among the goals in the management of blood glucose and coronary health. AGE’s affect the physiological profiles of proteins by creating cross-links, and they induce vascular dysfunction by stiffening blood vessels and myocardial tissue. Keeping HbA1c where your doctor wants it will keep you alive long enough to be chastised for decades.

References

Abiemo EE, Alonso A, Nettleton JA, Steffen LM, Bertoni AG, Jain A, Lutsey PL.
Relationships of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA).
Br J Nutr. 2012 Aug 30:1-8.

Afaghi A, Ziaee A, Afaghi M.
Effect of low-glycemic load diet on changes in cardiovascular risk factors in poorly controlled diabetic patients.
Indian J Endocrinol Metab. 2012 Nov;16(6):991-5.

Ajala O, English P, Pinkney J.
Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes.
Am J Clin Nutr. 2013 Mar;97(3):505-16.

Anastasios S Dontas, Nicholas S Zerefos, Demosthenes B Panagiotakos, and Dimitrios A Valis
Mediterranean diet and prevention of coronary heart disease in the elderly
Clin Interv Aging. 2007 March; 2(1): 109–115.

Barclay AW, Petocz P, McMillan-Price J, Flood VM, Prvan T, Mitchell P, Brand-Miller JC.
Glycemic index, glycemic load, and chronic disease risk–a meta-analysis of observational studies.
Am J Clin Nutr. 2008 Mar;87(3):627-37.

Bédard A, Riverin M, Dodin S, Corneau L, Lemieux S.
Sex differences in the impact of the Mediterranean diet on cardiovascular risk profile.
Br J Nutr. 2012 Oct 28;108(8):1428-34.

Chiu CJ, Liu S, Willett WC, Wolever TM, Brand-Miller JC, Barclay AW, Taylor A.
Informing food choices and health outcomes by use of the dietary glycemic index.
Nutr Rev. 2011 Apr;69(4):231-42.

Domínguez LJ, Bes-Rastrollo M, de la Fuente-Arrillaga C, Toledo E, Beunza JJ, Barbagallo M, Martínez-González MA.
Similar prediction of decreased total mortality, diabetes incidence or cardiovascular events using relative- and absolute-component Mediterranean diet score: The SUN cohort.
Nutr Metab Cardiovasc Dis. 2012 Mar 6.

Due A, Larsen TM, Mu H, Hermansen K, Stender S, Astrup A.
Comparison of 3 ad libitum diets for weight-loss maintenance, risk of cardiovascular disease, and diabetes: a 6-mo randomized, controlled trial.
Am J Clin Nutr. 2008 Nov;88(5):1232-41.

Ebbeling CB, Leidig MM, Sinclair KB, Seger-Shippee LG, Feldman HA, Ludwig DS.
Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults.
Am J Clin Nutr. 2005 May;81(5):976-82.

K. Eskesen, M. T. Jensen, S. Galatius, H. Vestergaard, P. Hildebrandt, J. L. Marott,
J. S. Jensen
Glycated haemoglobin and the risk of cardiovascular disease, diabetes and all-cause mortality in the Copenhagen City Heart Study
Journal of Internal Medicine. Vol 273, Iss 1, pp 94–101, January 2013

Hartog JW, Voors AA, Bakker SJ, Smit AJ, van Veldhuisen DJ.
Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications.
Eur J Heart Fail. 2007 Dec;9(12):1146-55.

Konstantinidou V, Covas MI, Sola R, Fitó M.
Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans.
Mol Nutr Food Res. 2013 Feb 18. doi: 10.1002/mnfr.201200613. [Epub ahead of print]

Kuhlmann M., Levin N.
Interaction between Nutrition and Inflammation in Hemodialysis Patients. in “Cardiovascular Disorders in Hemodialysis”
Ronco C. Vicenza and Brendolan A. Vicenza, editors. Basel, Karger, 2005, vol 149, pp 200-207

Lagiou P, Sandin S, Weiderpass E, Lagiou A, Mucci L, Trichopoulos D, Adami HO.
Low carbohydrate-high protein diet and mortality in a cohort of Swedish women.
J Intern Med. 2007 Apr;261(4):366-74.

Lagiou P, Sandin S, Lof M, Trichopoulos D, Adami HO, Weiderpass E.
Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study.
BMJ. 2012 Jun 26;344:e4026. doi: 10.1136/bmj.e4026.

Lajous M, Boutron-Ruault MC, Fabre A, Clavel-Chapelon F, Romieu I.
Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women.
Am J Clin Nutr. 2008 May;87(5):1384-91.

Talya Lavi, RD, Avraham Karasik, MD, Nira Koren-Morag, PHD, Hannah Kanety, PHD,
Micha S. Feinberg, MD, Michael Shechter, MD, MA
The Acute Effect of Various Glycemic Index Dietary Carbohydrates on Endothelial Function in Nondiabetic Overweight and Obese Subjects
College of Cardiology Vol. 53, No. 24, 2009: 2283-2287

Martínez-González MA, de la Fuente-Arrillaga C, Nunez-Cordoba JM, Basterra-Gortari FJ, Beunza JJ, Vazquez Z, Benito S, Tortosa A, Bes-Rastrollo M.
Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study.
BMJ. 2008 Jun 14;336(7657):1348-51

Martínez-González MA, García-López M, Bes-Rastrollo M, Toledo E, Martínez-Lapiscina EH, Delgado-Rodriguez M, Vazquez Z, Benito S, Beunza JJ.
Mediterranean diet and the incidence of cardiovascular disease: a Spanish cohort.
Nutr Metab Cardiovasc Dis. 2011 Apr;21(4):237-44.

Massaro M, Carluccio MA, De Caterina R.
Direct vascular antiatherogenic effects of oleic acid: a clue to the cardioprotective effects of the Mediterranean diet.
Cardiologia. 1999 Jun;44(6):507-13.

Peppa M, Raptis SA.
Advanced glycation end products and cardiovascular disease
Curr Diabetes Rev. 2008 May;4(2):92-100.

Rose Marie Robertson, MD; Lynn Smaha, MD, PhD
Can a Mediterranean-Style Diet Reduce Heart Disease?
Circulation. 2001; 103: 1821-1822

Valeria Tarabusi, Carla Cavazza, Francesca Pasqui, Alessandra Gambineri, Renato Pasquali
Quality of diet, screened by the Mediterranean diet quality index and the evaluation of the content of advanced glycation endproducts, in a population of high school students from Emilia Romagna
Mediterranean J Nutrition and Metabolism. Sep 2010, Vol 3, Iss 2, pp 153-157

Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Fuecker K, Hanefeld M.
Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level.
Diabetes Care. 2000 Dec;23(12):1830-4.

Uchiki T, Weikel KA, Jiao W, Shang F, Caceres A, Pawlak D, Handa JT, Brownlee M, Nagaraj R, Taylor A.
Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics).
Aging Cell. 2012 Feb;11(1):1-13.

Wolever TM, Gibbs AL, Mehling C, Chiasson JL, Connelly PW, Josse RG, Leiter LA, Maheux P, Rabasa-Lhoret R, Rodger NW, Ryan EA.
The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein.
Am J Clin Nutr. 2008 Jan;87(1):114-25.

Yurong Zhang, Gang Hu, Zuyi Yuan, Liwei Chen
Glycosylated Hemoglobin in Relationship to Cardiovascular Outcomes and Death in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
PLoS ONE 7(8): e42551

Ziaee A, Afaghi A, Sarreshtehdari M.
Effect of low glycemic load diet on glycated hemoglobin (HbA1c) in poorly-controlled diabetes patients.
Glob J Health Sci. 2011 Dec 29;4(1):211-6.

*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.
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.