Posts

Age-Related Macular Degeneration

eyeglasses-and-eye-chartWhat is AMD?

When given a checklist to rank their greatest health-related fears, most adults didn’t choose cancer or heart disease as number one. Of more than ten thousand people surveyed during an international study conducted by India’s Prasad Eye Institute, over ninety percent chose blindness (Giridhar, 2002). In a survey commissioned by Pfizer, twice as many respondents feared blindness as premature death (Pfizer, 2008).  But mere fear of something doesn’t make it go away. Taking action, though, could.

Age-related macular degeneration, or AMD, is a degenerative disease of the retina (the thin layer of nerve cells lining the back of the eyeball) that causes progressive loss of central vision, where the macula interprets details. Photoreceptor cells in the macula convert light into electrical messages that are transferred to the brain by the optic nerve.  If these cells degenerate, central vision does likewise. Risk for macular degeneration increases with age, and is the most common cause of vision loss in those over sixty.  It’s estimated that eight million people in the United States over age fifty-five have one or both eyes affected by intermediate AMD (Bressler, 2003). Because life expectancy has increased, the number of AMD cases is likely to rise to three million by 2020 (Friedman, 2004), thus becoming a major public health problem.

There are two types of AMD: dry and wet. The dry form accounts for more than 90% of all cases, and is characterized by yellowish-whitish deposits, called drusen, that accumulate behind the macula. Drusen are composed of the glycoprotein and glycolipid waste products of the photoreceptor cells, and they interfere with the blood supply to those cells.  In dry AMD, vision loss is gradual over the course of many years, often affecting only one eye. The wet form of AMD is identified by the appearance of newly created abnormal blood vessels growing under the macula. Unfortunately, these vessels leak, bleed and scar the macula, distorting or destroying central vision. Because the blood and fluid lift the macula out of position at the back of the eye, damage occurs rapidly. Wet AMD is the leading cause of irreversible legal blindness.

What Are The Risk Factors?

Age and race are common factors. As Caucasians age from their 60s to their late 70s, the risk changes from about 2% to almost 30%. No such increase is seen in other populations. Smoking reduces the amount of oxygen that reaches the eye—and other organs—and precludes the use of nutritional interventions that may prevent AMD in the first place. It’s been discovered that certain supplements related to vitamin A are causative of respiratory disease among smokers, including cancer. As with many diseases, family history plays a role, as well as a gene labeled CFH, compliment factor H, which is probably implicated in more than half the AMD cases in the United States (Chakravarthy, 2010) (Klein, 2005).

What Are The Symptoms?

The need for increasingly bright illumination (especially for close work), difficulty in adapting to lower levels of illumination (as when entering a dimly lit restaurant), increasing blurriness of printed material, reduced intensity of bright colors, and a blurred or blind spot combined with a loss of central visual sharpness are signs of dry AMD. Wet AMD may present as crookedness or waviness of lines known to be straight, a street sign that is out of focus, objects appearing farther away than they actually are, and a decrease in central vision, among others. Because a good eye can compensate for one affected by AMD, symptoms might not be noticed right away.

Pupil dilation by your eye doctor will enable him or her to see your retina through a tool called a slit lamp, which allows examination through a kind of microscope. The doctor will look for drusen and for other suspicious features. Because new blood vessels beneath the retina are hard to see, the doctor will look for other signs of wet AMD that may include bleeding, fluid behind the retina or elevation of the retina. Should these be identified, further evaluation is probably needed.

How About Treatment?

Lifestyle changes (and medications) can alter the progress of dry AMD. Antioxidant deficiencies, notably of zinc, and vitamins A, C, and E, have been noted in age-related macular degeneration (Age-Related Eye Disease Study [AREDS] Group, 2001). These substances prevent free radicals and unstable oxygen from damaging the retina, and are commonly found in leafy greens, colorful vegetables (oranges, yellows and purples), and fruits. A person diagnosed with AMD should look at diet anyway, so why not take the preventive route? Do it now. Lowering intake of animal fats and getting a little exercise to drop a few pounds is part of the regimen.

Early in this century the Dutch conducted a review of work that started in the 1990’s, examining an over-55 population of middle-class suburbanites who had at least one risk factor for AMD. Of almost six thousand at-risk subjects, all of whom had supplied a comprehensive dietary inventory, fewer than ten percent experienced incident AMD after an 8-year follow-up. It was noted that those with the highest intakes of all four antioxidant compounds (Zn, A, C, E) had a significant reduction in risk of disease (vanLeeuwen, 2005).

An earlier British study acknowledged the protective function of vitamins A, C, and E, concurrently citing the role of zinc in retinal metabolism and that of selenium as anti-oxidative. High serum levels of carotenoids, the yellow to red pigments in plants that are concentrated in the retina, are associated with reduced risk of AMD. A serendipitous discovery in this elderly group, though not directly related to its goal, found that the essential omega-6 fat, gamma-linolenic acid (GLA), helps in dry eye conditions. The value of the omega-3 fats in retinal development is reiterated (Brown, 1998).

Harvard investigations found that omega-3 fats from fish oil and fish consumption reduced risk for AMD, especially among smokers (Seddon, 2006), whose additional risks include uncontrolled cholesterol and diabetes (Tomany, 2004). Most recently, investigators at the University of Alberta found DHA, the omega-3 that partners with EPA in fish and fish oil, able to block the accumulation of toxic molecules behind the retina (Dornstauder, 2012). Keep in mind that DHA must be balanced with EPA, at a ratio of approximately 3:1, EPA:DHA. The reason? Alone, or in unbalanced supplementation, DHA can be excitatory, despite its known connection to eye and brain health.

A randomized trial recounted by Harvard Medical School says that markers of inflammation provide an environment conducive to AMD. Homocysteine and C-reactive protein are analytes that can be mitigated by the judicious use of vitamins B12, B6, and folic acid, all of which are related to the reduced incidence of coronary episodes. Together, these supplements proved effective in reducing incidence of AMD in a considerably large group enrolled in a women’s cardiovascular study (Christen, 2009).  That these markers are implicated in eye-related pathologies had been established earlier (Seddon, 2004).

Getting antioxidants from foods is held by traditional medicine to be the best route, but this may be a misguided stance. The general food supply has been denigrated by less-than-stellar corporate farming practices that use chemical soil enhancers and biocides that linger on food surfaces. Dousing stored seeds with pesticides that eventually appear in the stems, leaves, roots, and fruits of plants, followed by sloppy storage and shipping practices negate the veracity of obtaining all the nutrition we need from our food. It’s bad enough that much food lacks nutrition, but it’s an insult that our livers have to detoxify it, too. Add all this to what happens in a careless kitchen and we can establish the need for supplementation.

References

Age-Related Eye Disease Study Research Group.
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.
Arch Ophthalmol. 2001 Oct;119(10):1417-36.

Age-Related Eye Disease Study Research Group.
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9.
Arch Ophthalmol. 2001 Oct;119(10):1439-52.

Pia Allegri, Antonio Mastromarino, Piergiorgio Neri
Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up
Clinical Ophthamology. October 2010 Volume 2010:4 Pages 1201 – 1206

Beatty S, Koh H, Phil M, Henson D, Boulton M.
The role of oxidative stress in the pathogenesis of age-related macular degeneration.
Surv Ophthalmol. 2000 Sep-Oct;45(2):115-34.

Bressler NM, Bressler SB, Congdon NG, Ferris FL 3rd, Friedman DS, Klein R, Lindblad AS, Milton RC, Seddon JM; Age-Related Eye Disease Study Research Group.
Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.
Arch Ophthalmol. 2003 Nov;121(11):1621-4.

Brown NA, Bron AJ, Harding JJ, Dewar HM.
Nutrition supplements and the eye.
Eye (Lond). 1998;12 ( Pt 1):127-33.

Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C, Zlateva G, Buggage R, Pleil A, Mitchell P.
Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis.
BMC Ophthalmol. 2010 Dec 13;10:31.

Cho E, Hung S, Willett WC, Spiegelman D, Rimm EB, Seddon JM, Colditz GA, Hankinson SE.
Prospective study of dietary fat and the risk of age-related macular degeneration.
Am J Clin Nutr. 2001 Feb;73(2):209-18.

Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE.
Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study.
Arch Intern Med. 2009 Feb 23;169(4):335-41.

Delcourt C, Carrière I, Cristol JP, Lacroux A, Gerber M.
Dietary fat and the risk of age-related maculopathy: the POLANUT study.
Eur J Clin Nutr. 2007 Nov;61(11):1341-4. Epub 2007 Feb 14.

Dornstauder B, Suh M, Kuny S, Gaillard F, Macdonald IM, Clandinin MT, Sauvé Y.
Dietary Docosahexaenoic Acid Supplementation Prevents Age-Related Functional Losses and A2E Accumulation in the Retina
Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2256-65. Print 2012.

Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA.
Complement factor H polymorphism and age-related macular degeneration.
Science. 2005 Apr 15;308(5720):421-4. Epub 2005 Mar 10.

Friedman DS, O’Colmain BJ, Muñoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J; Eye Diseases Prevalence Research Group.
Prevalence of age-related macular degeneration in the United States.
Arch Ophthalmol. 2004 Apr;122(4):564-72.

Giridhar P, Dandona R, Prasad MN, Kovai V, Dandona L.
Fear of blindness and perceptions about blind people. The Andhra Pradesh Eye Disease Study.
Indian J Ophthalmol. 2002 Sep;50(3):239-46.

Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R.
A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32. Epub 2005 May 3.

Hodge WG, Schachter HM, Barnes D, Pan Y, Lowcock EC, Zhang L, Sampson M, Morrison A, Tran K, Miguelez M, Lewin G.
Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a systematic review.
Ophthalmology. 2006 Jul;113(7):1165-72; quiz 1172-3, 1178.

Johnson EJ, Schaefer EJ.
Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration.
Am J Clin Nutr. 2006 Jun;83(6 Suppl):1494S-1498S.

Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J.
Complement factor H polymorphism in age-related macular degeneration.
Science. 2005 Apr 15;308(5720):385-9. Epub 2005 Mar 10.

Pfizer
Twice as many people fear blindness more than premature death
Friday, 7 March, 2008
http://www.ncbi.ie/news/press-releases/2008-03-07_twice-as-many-people-fear-blindness-more-than-premature-death

Pratt S.
Dietary prevention of age-related macular degeneration.
J Am Optom Assoc. 1999 Jan;70(1):39-47.

Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, et al.
Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group.
JAMA. 1994 Nov 9;272(18):1413-20.

Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N.
Association between C-reactive protein and age-related macular degeneration.
JAMA. 2004 Feb 11;291(6):704-10.

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

Anxious About Anxiety?

mid-adult-male-portraitYou’re not anxious about going on vacation or performing a pleasant task. You’re enthusiastic (but not enthused). You could be anxious about going to the dentist or to defend your last income tax return. Here, you’re entertaining a feeling of dread or apprehension, probably lacking clear justification.  Anxiety results from a subjective way of looking at a situation in the absence of a clear and actual danger. Of course, the sweating, increased pulse, and tension coupled with self-doubt about being able to handle the matter tell a different story. Sometimes respirations increase, the mouth gets dry and the intestines gurgle. All this is part of a defense mechanism. Anxiety can be particular, such as a panic attack in a crowd of people, in which case the stimulus can be identified. Or it may be generalized, being a long-term experience with no explanation of its cause. Obsessive-compulsory disorder (OCD) is an anxious state characterized by quandaries of uncertainty and compulsions to act. If the act is frustrated, the uncertainty remains and anxiety is intensified. Anxiety is considered a normal, but transient, response to stress, encouraging a person to take action in order to deal with what is perceived to be a difficult situation.

What’s The Risk?

Women are twice as likely as men to become anxious, mostly because of hormones and the archaic expectations that women are supposed to take care of everybody else before themselves. Age plays a minor role, in that OCD, separation anxiety and social phobias that include panic disorder show up in childhood and the teenage years. Early identification and treatment can forestall later problems. Certain environmental factors, such as poverty, separation from family, overly strict parents, family conflicts, anxious family members and lack of support can induce anxiety disorders. That anxiety runs in families is accepted, but it’s not known if the onset is genetic or learned, or both.

Physiologically, anxiety may be prompted by faulty brain chemistry, where an imbalance of serotonin, for instance, may result in irregular moods and emotions. There may be a structural fault, too.  The amygdala is the part of the brain in charge of processing emotional reactions and memory consolidation, including the recollection of fear.  If it’s overactive, this structure will heighten the fear response and increase anxiety in social situations.   Non-structural physical concerns, such as health problems, can cause anxiety.  Diabetes, alcoholism, heart disease, odd sensations that have no apparent cause, and thyroid disease are a few.

How Do I Handle Anxiety?

Besides the traditional psychotherapy practices and anti-anxiety medications, there are a few things you can do to take charge. First, you need to know that withdrawal from a psychoactive drug can cause anxiety. So, weaning from benzodiazepines causes the thing for which you took the drug in the first place. But beta-blockers, typically used for blood pressure control, have no such effect. They’re used off label to control rapid heartbeat, nervousness, trembling voice and shaky hands that accompany anxiety attacks. Alcohol withdrawal causes anxiety in many people.

Alternative approaches to anxiety treatment include things you can do and things you can swallow. Some modalities that require active participation include music therapy, art therapy, aromatherapy and meditation. With these you have to turn the music on, wield a paintbrush, light a candle, or think about pleasant things. But many people are unwilling or unable to be so engaged because of time constraints, family and job obligations, or simple faineance. Deglutition is the answer.

Options to psychological interventions for anxiety were sought in order to overcome limitations on time and resources. Because of adverse side-effects, alternatives to anxiolytic drugs also were explored. There is a shrub from the South Pacific islands that’s been used for centuries to calm the nerves, Piper methysticum, commonly known as kava kava. In a meta-analysis performed by the Cochrane Database at England’s Exeter University, researchers found that anxious subjects who took kava extract as a sole constituent in their treatment experienced a substantial reduction in symptoms compared to those taking a placebo (Pittler, 2000, 2003). One of the differences between a natural substance and a synthetic one is the time it takes to demonstrate effectiveness.  With a natural substance—in this example, herbal—you get the active ingredient and all the supportive components of the plant. Many enjoy an unexplainable synergy.  With a synthetic one—a drug—you get an isolated chemical that is not toned down by collaborative elements. Although earlier study found kava to be effective at taming anxious moments, it took eight weeks for kava’s superiority to placebo to be displayed (Volz, 1997).

Benzodiazepines are the drugs commonly used to treat anxiety. Their side effects, besides excessive drowsiness and decreased alertness, include paradoxical consequences, such as aggression, impulsivity, and irritability. Cognitive impairment and tolerance can result, as well. Tapering off these medications requires deliberation and a watchful eye. Using kava kava during such an ordeal, patients who were weaned from the drugs while being introduced to the herbal showed good tolerance and improved symptoms over a period of two weeks in a five-week trial in Germany (Malsch, 2001).

Generalized anxiety disorder has responded well to another folk remedy, passion flower. In a study comprising three dozen individuals, half received passion flower plus placebo and half received a benzodiazepine plus placebo in a one-month trial. The outcome showed both the herb and the drug to be effective in controlling anxiety symptoms. The drug, with rapid onset of action, impaired job performance (Akhondzadeh, 2001). The herb did not. Pharmacologically, extracts of the upper parts of the passion flower plant are most dynamic (Dhawan, 2001).

If you’ve taken fish oil for heart and brain health, that’s good. It’s been discovered that low levels of omega-3 fatty acids play a significant role in a number of mental irregularities (Buydens-Branchley, 2008) and that mood disorders respond especially well to omega-3 supplementation, with EPA getting better press than its companion, DHA (Ross, 2007). With a ratio of 3 to I, EPA to DHA, a fish oil product called Kirunal appears more than adequate to satisfy the mono- or adjunctive therapy approach in treating mood anomalies. For decades it’s been given that omega-3 fats are effective in the treatment of major depressive disorders, so it is reasonable to submit that they be likewise in anxiety disorders (Ross, 2009). If the presence of a substance yields a specific result, then the absence of that substance should yield the opposite. A deficit of n-3 fats has been identified in the red cell membranes of anxious persons (Greena, 2006), specifically those with social anxieties. Overall, it’s been proposed that human foods be supplemented with omega-3 fats as a strategy to improve behaviors and cognitive functions (Vinot, 2011). This makes one wonder if the education community needs to sit up and take notice. If that’s an inflammatory statement, n-3 supplementation can ameliorate that while reducing self-induced anxiety (Kiecolt-Glaser, 2011).

A relative newcomer on the anti-anxiety supplement stage is curcumin, the active ingredient of the turmeric spice common to Southern Asian and Middle Eastern cuisine.  Known predominantly as an anti-inflammatory agent, curcumin was found to have antidepressant like activity similar to tricyclic antidepressants, such as fluoxetine and imipramine (Sanmukhani, 2011). Because it is a natural substance, doses of curcumin used in an Indian trial were extraordinarily high, at 100 mg per kilogram of body weight, which equates to about 6,800 mg (6.8 grams) for a 150-pound person. Lesser dosages, from 10 to 80 mg/kg, demonstrated a positive effect on serotonin and dopamine activity, acting similarly to commonly prescribed drugs (Kulkami, 2008).

If you maintain a healthy diet, making sure to get the full array of macro and micro minerals, especially magnesium and zinc, as well as sufficient B vitamins, focusing on B 12, you’ll be able to avoid at least one cause of anxiety. Cutting back on alcohol and caffeine, and getting ample sleep are others. A caveat: before embarking on a supplement regimen to address anxiety, check with a healthcare professional to look for interactions with medicines and foods.

References

Andreatini R, Sartori VA, Seabra ML, Leite JR.
Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study.
Phytother Res. 2002 Nov;16(7):650-4.

Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M.
Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam.
J Clin Pharm Ther. 2001 Oct;26(5):363-7.

Buydens-Branchey L, Branchey M.
n-3 polyunsaturated fatty acids decrease anxiety feelings in a population of substance abusers.
J Clin Psychopharmacol. 2006 Dec;26(6):661-5.

Buydens-Branchey L, Branchey M, Hibbeln JR.
Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusers.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):568-75. Epub 2007 Nov 1.

Dhawan K, Kumar S, Sharma A.
Anti-anxiety studies on extracts of Passiflora incarnata Linneaus.
J Ethnopharmacol. 2001 Dec;78(2-3):165-70.

Dhawan K, Kumar S, Sharma A.
Anxiolytic activity of aerial and underground parts of Passiflora incarnata.
Fitoterapia. 2001 Dec;72(8):922-6.

Ernst E.
The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto, and Kava.
Ann Intern Med. 2002 Jan 1;136(1):42-53.

Ernst E.
Herbal remedies for anxiety – a systematic review of controlled clinical trials.
Phytomedicine. 2006 Feb;13(3):205-8. Epub 2005 Aug 15.

G. Fontani, F. Corradeschi, A. Felici, F. Alfatti, S. Migliorini, L. Lodi
Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects
European Journal of Clinical Investigation. Vol 35, Iss 11, pages 691–699, Nov 2005

Pnina Greena, Haggai Hermeshb, Assaf Monselisec, Sofi Marom, Gadi Presburger, Abraham Weizman
Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder
European Neuropsychopharmacology. Feb 2006; 16(2): 107-113

Harauma A, Moriguchi T.
Dietary n-3 fatty acid deficiency in mice enhances anxiety induced by chronic mild stress.
Lipids. 2011 May;46(5):409-16. Epub 2011 Feb 7.

Jadoon A, Chiu CC, McDermott L, Cunningham P, Frangou S, Chang CJ, Sun IW, Liu SI, Lu ML, Su KP, Huang SY, Stewart R.
Associations of polyunsaturated fatty acids with residual depression or anxiety in older people with major depression.
J Affect Disord. 2012 Feb;136(3):918-25. Epub 2011 Nov 21.

Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Glaser R.
Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial.
Brain Behav Immun. 2011 Nov;25(8):1725-34. Epub 2011 Jul 19.

Kinrys G, Coleman E, Rothstein E
Natural remedies for anxiety disorders: potential use and clinical applications.
Depress Anxiety. 2009;26(3):259-65.

Kulkarni SK, Bhutani MK, Bishnoi M.
Antidepressant activity of curcumin: involvement of serotonin and dopamine system.
Psychopharmacology (Berl). 2008 Dec;201(3):435-42. Epub 2008 Sep 3.

Lakhan SE, Vieira KF.
Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review.
Nutr J. 2010 Oct 7;9:42.

Malsch U, Kieser M.
Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines.
Psychopharmacology (Berl). 2001 Sep;157(3):277-83.

McBride S, Graydon J, Sidani S, Hall L.
The therapeutic use of music for dyspnea and anxiety in patients with COPD who live at home.
J Holist Nurs. 1999 Sep;17(3):229-50.

Pittler MH, Ernst E.
Efficacy of kava extract for treating anxiety: systematic review and meta-analysis.
J Clin Psychopharmacol. 2000 Feb;20(1):84-9.

Pittler MH, Ernst E.
Kava extract for treating anxiety.
Cochrane Database Syst Rev. 2003;(1):CD003383.

Ross BM, Seguin J, Sieswerda LE.
Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid?
Lipids Health Dis. 2007 Sep 18;6:21.

Brian M. Ross
Omega-3 polyunsaturated fatty acids and anxiety disorders
Prostaglandins, Leukotrienes and Essential Fatty Acids. Nov 2009; 81(5): 309-312

Saeed SA, Bloch RM, Antonacci DJ.
Herbal and dietary supplements for treatment of anxiety disorders.
Am Fam Physician. 2007 Aug 15;76(4):549-56.
Sanmukhani J, Anovadiya A, Tripathi CB.
Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study.
Acta Pol Pharm. 2011 Sep-Oct;68(5):769-75.

Song C, Li X, Leonard BE, Horrobin DF
Effects of dietary n-3 or n-6 fatty acids on interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats.
J Lipid Res. 2003 Oct;44(10):1984-91. Epub 2003 Jul 1.

Vinot N, Jouin M, Lhomme-Duchadeuil A, Guesnet P, Alessandri JM, Aujard F, Pifferi F.
Omega-3 fatty acids from fish oil lower anxiety, improve cognitive functions and reduce spontaneous locomotor activity in a non-human primate.
PLoS One. 2011;6(6):e20491. Epub 2011 Jun 7.

Volz HP, Kieser M.
Kava-kava extract WS 1490 versus placebo in anxiety disorders–a randomized placebo-controlled 25-week outpatient trial.
Pharmacopsychiatry. 1997 Jan;30(1):1-5.

tYehuda S, Rabinovitz S, Mostofsky DI.
Mixture of essential fatty acids lowers test anxiety.
Nutr Neurosci. 2005 Aug;8(4):265-7.

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

The Super Enzyme Nattokinase

NattoThere probably is more than one way to skin a cat, but why would you do that in the first place? What do you do with the pelt, make a coat? or the flesh? Stew? Nah. Still there is more than one way to approach a job and to get it done. This philosophy applies to healthcare as well as to mechanical tasks. Long before there was what we now call conventional medicine, there was folk medicine, which today falls into the category of integrative, or complementary, or alternative medicine. To the surprise, and even chagrin, of the orthodox model, some of these folk remedies actually work—and they do so without side effects or contraindications. Take honey, for example. It’s been around since prehistory and has been used to ease sore throats and upper respiratory troubles since then. And…it’s making a comeback (Cohen, 2012) (Paul, 2007) (Fashner, 2012).

One of the Creator’s gifts to mankind is derived from a cultural food called natto, a traditional Japanese comestible made by fermenting boiled soybeans with Bacillus subtilis, a type of soil bacterium commensal to the human gut. This bacterial strain is noted for contributing to a healthy microflora and for enhancing the status of vitamin K2. The product extracted from natto is called nattokinase, an enzyme that is able to break the peptide bonds in proteins (Fujita, 1993) using a biochemical activity resembling trypsin, which is a proteolytic enzyme made by the pancreas to separate proteins into amino acids. Despite its name, nattokinase is not a kinase enzyme. That is a catalyst in phosphorus-related functions. Instead, it’s a subtilisin enzyme, as its name suggests. Because it can break apart proteins, it exhibits potent fibrinolytic characteristics (Fujita, 1993) (Sumi, 1987), hence its use in complementary and alternative medicine as a clot-buster. The term “fibrinolytic” means that a substance is able to liquefy coagulated blood by dissolving fibrin, the elastic, stringy protein that forms a kind of mesh to attract and hold platelets to make a clot. This is an activity we want when cut, but not inside a blood vessel.

People have used nattokinase to attend to cardiovascular matters, including stroke, angina, deep vein thrombosis, atherosclerosis, intermittent claudication, and even hemorrhoids and varicose veins. (Cesarone, 2003) (Fujita, 1993). Because of its fibrinolytic activity at the blood vessel wall, where a thrombus is likely to form, nattokinase is thought to be helpful in treating atherosclerosis (Suzuki, March 2003; July 2003).

Although nattokinase is not to be taken with aspirin or other blood thinners, including fish oil (separate by a two-hour window), it works differently. Aspirin inhibits an enzyme known as cyclo-oxygenase (COX). COX activates a chemical called thromboxane A2, which makes platelets stick together to form a plug over a damaged area of a blood vessel, as in a shaving nick. The work of aspirin cannot be undone because it lasts as long as a platelet is alive and working, about a week (Roth, 1975). This makes us wonder why aspirin is recommended every day instead of only once—or maybe twice—a week.  Clots are aggregates of platelets, red blood cells and fibrin. If a clot stays still, it’s a thrombus; if it moves, it’s an embolus. Nattokinase works by removing fibrin from the equation; aspirin prevents stickiness of platelets.

As promising as nattokinase can be, it is not without its critics—a common element with alternatives to allopathic medicine. There have been no definitive outcomes regarding this agent as an alternative to conventional treatments using aspirin, clopidogrel (Plavix) or warfarin (Coumadin). One factor is the dissolution and bioavailability of nattokinase. The effects of gastric acid on nattokinase are unknown, but the enteric coated form, at 1.3 grams three times a day, seems to increase measures of fibrinolytic activity for up to eight hours after ingestion (Sumi, 1990).

When fibrin accumulates in blood vessels, it almost always causes thrombosis, possibly leading to a cardiac event. You see, this is a property of wound healing. Insults to an arterial wall, as from chronic inflammation, reactive oxygen species or illness, may hasten the inflammatory cascade that demonstrates the activation of platelets and the eventual formation of plaque-producing macrophages, all in the name of damage repair. This is where anti-inflammatory agents and anti-oxidants get their celebratory publicity…and it isn’t mere hype. This also is where nattokinase gains attention as a potential functional food additive (Peng, 2005).

If arteries are clear, and if blood has the proper viscosity, elevated blood pressure will likely be a non-issue, but this appears to be more rare than common. At Yonsei University’s Institute of Science for Ageing, in Seoul, Korea, researchers wondered about the relevance of nattokinase to blood pressure homeostasis. Studying untreated hypertensive subjects, they found that 2000 fibrinolytic units (FU)—about 100 mg—of nattokinase for eight weeks effected a drop of almost 6 points in both diastolic and systolic readings (Kim, 2008). A similar finding was reported by the pharmacology department of Hiroshima University, in Japan, a few years later (Fujita, 2011). To add feathers to the cap, nattokinase activity may parallel that of the ACE inhibitors  commonly prescribed to treat hypertension (Murakami, 2012).

More study on this fermented soybean product is needed, but its future is promising. Nattokinase does not interact with any foods and does not interfere with blood tests. It should be avoided by pregnant women for lack of safety studies. Those scheduled for surgery are admonished to discontinue using nattokinase, or any other blood-thinning agent, a couple of weeks beforehand. But we’ll leave on an encouraging note:  nattokinase may have a place in Alzheimer’s treatment as a degradation agent for amyloid fibrils (Hsu, 2009).

References

Cesarone MR, Belcaro G, Nicolaides AN, Ricci A, Geroulakos G, Ippolito E, Brandolini R, et al
Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial.
Angiology. 2003 Sep-Oct;54(5):531-9.

Cohen HA, Rozen J, Kristal H, Laks Y, Berkovitch M, Uziel Y, Kozer E, Pomeranz A, Efrat H.
Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study.
Pediatrics. 2012 Sep;130(3):465-71. doi: 10.1542/peds.2011-3075. Epub 2012 Aug 6.

Fashner J, Ericson K, Werner S.
Treatment of the common cold in children and adults.
Am Fam Physician. 2012 Jul 15;86(2):153-9.

Fujita M, Nomura K, Hong K, Ito Y, Asada A, Nishimuro S.
Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan.
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1340-7.

Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S.
Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.
Biol Pharm Bull. 1995 Oct;18(10):1387-91.

Fujita M, Ohnishi K, Takaoka S, Ogasawara K, Fukuyama R, Nakamuta H.
Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.
Biol Pharm Bull. 2011;34(11):1696-701.

GUO Ting, YAO Wen-bing, GAO Xiang-dong
Study on the fibrinolytic activity and the mechanism of nattokinase
Chinese Journal of Biochemical Pharmaceutics 2004-04

Ruei- Amyloid-degrading ability if nattokinase from Bacillus subtilis Natto
Lin Hsu, Kung-Ta Lee, Jung_Hao Wang, Lily Y.L. Lee and rRta P.Y. Chen
J of Agr and Food Chem. 2009; 57: 503-508

Keiko Murakami, Naoki Yamanaka, Katsunori Ohnishi, Minoru Fukayama and Masataka Yoshino
Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food
Food Funct., 2012,3, 674-678

Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH.
Effects of nattokinase on blood pressure: a randomized, controlled trial.
Hypertens Res. 2008 Aug;31(8):1583-8. doi: 10.1291/hypres.31.1583.

Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM Jr.
Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents.
Arch Pediatr Adolesc Med. 2007 Dec;161(12):1140-6.

Peng Y, Yang X, Zhang Y.
Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo.
Appl Microbiol Biotechnol. 2005 Nov;69(2):126-32. Epub 2005 Nov 12.

G J Roth and P W Majerus
The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein.
J Clin Invest. 1975 September; 56(3): 624–632.

Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H.
A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet.
Experientia. 1987 Oct 15;43(10):1110-1.

Sumi H, Hamada H, Nakanishi K, Hiratani H.
Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.
Acta Haematol. 1990;84(3):139-43.

Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T, Umemura K.
Dietary supplementation with fermented soybeans suppresses intimal thickening.
Nutrition. 2003 Mar;19(3):261-4.

Suzuki Y, Kondo K, Matsumoto Y, Zhao BQ, Otsuguro K, Maeda T, Tsukamoto Y, Urano T, Umemura K.
Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery.
Life Sci. 2003 Jul 25;73(10):1289-98.

Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A.
The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1.
J Biol Chem. 2001 Jul 6;276(27):24690-6. Epub 2001 Apr 26.

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

You Expect Me To Believe That?

fishoil-hookSome things just belong together. Not too many of us eat only the meringue from the lemon pie. Sauerkraut on a bun without the sausage isn’t quite the same gustatory delight. And sometimes the aunt is more fun when in the company of the uncle. Such is the case with essential fatty acids. The omega-3’s can do their job without the omega-6’s, but the outcome will eventually be out of whack. It’s this imbalance that wrought the nefarious genius of a twisted, fear-huckstering fish oil report, so carefully crafted that the typical reader comes to believe that black is white.

The study reported in the Journal of the National Cancer Institute determined a positive relationship of non-vegetable sourced omega-3 fatty acids to prostate cancer. If non-vegetable, that leaves fish oil, known better for its downstream n-3 fats, EPA and DHA, than for the mother n-3, alpha-linolenic acid. The concern with this proposition is that the authors seem to have gone from home plate to home plate, in a 360-foot path without ever touching any of the bases. Healthy incredulity befits the reading of a ‘scientific’ paper. That leaves questions that most of us don’t ponder, including these:  Why would anyone take n-3 fats without also taking n-6 complements? Did any of the subjects bear a pre-existing pathology? Were the supplements, if used, of sufficiently high quality, as you would expect from a cGMP-obligated company? (The term “pharmaceutical grade” means only that toxins have been removed, and is otherwise unregulated, since many products that call themselves fish oil are not oils but ethyl esters instead of triglycerides.) Is it possible that individuals were removed from the study because they got healthy all of a sudden? Not to be too picky, but what were the capsules themselves made from, if supplements are to blame? Could the supplements have been combined with active pharmaceuticals or with contraindicated other supplements? Not finally, but at least additionally, why is it so that countries whose cuisine is dominated by fish—Scandinavia or Japan—do not also present a high level of prostate cancer? Funny thing:  this study failed to tell us where the men in this investigation got their omega-3 fats. The dollar store? Canned tuna? Maybe from the fish they ate an hour prior to the blood draw?

The Public Library of Science has a journal called PLoS One. It covers primary research in science and medicine, submissions of which are subjected to intense scrutiny and peer review. However, the Journal does invite post-publication discussion and critique. In its April, 2013 issue, it printed an Icelandic study on consumption of fish products and the risk of prostate cancer. There were almost 2300 men, aged 67 and up, in this four-year project. Except for processed fish that was salted or smoked, fish oil or very high fish consumption was determined not to be associated with early or midlife prostate cancer risk (Torfadottir, 2013). Hmm. Go figure. Earlier Canadian meta-analysis discovered a 63% reduction in prostate-cancer-specific mortality among fish eaters, but no incipient protective effect by fish ingestion (Szymanski, 2010). That means eating fish did not prevent disease. There are other causes, such as too much conventionally raised red meat.

There is a strong suggestion in a Harvard study that total fat and certain saturated fatty acids may be implicated in prostate disease incidence, but that, “Among all men, those with the highest omega-3 docosahexaenoic acid and total marine fatty acid intakes were 40% less likely to die from prostate cancer,” adding that “…high marine omega-3 fatty acid intake may improve disease-specific survival for all men” (Epstein, 2012). Although the source of DHA is not identified in the study in question, an Italian work cited the 22:6 n-3 as protective against physiological activities involved in the progression of prostate cancer cells (Bianchini, 2012).  Marshall University mice that were fed a high n-3 diet containing fish oil concentrate presented with a decreased expression of genes expected to increase proliferation of prostate cancer cells by virtue of lowering estradiol values (Akinsete, 2012).

What about the n-6 to n-3 ratio we mentioned earlier?  Glad you asked. In no particular order, try reading these authors  to get the picture that n-3 fats need the accompaniment of the n-6 fats: (vanJaarsveld, 1997) (Ramirez0Silve, 2011) (Caramia, 2008) (Wijendran, 2004) (Simopoulos, 2002, 2008) (Gomez, 2011) (Yehuda, 1993, 1996). The additional info you need to find these is at the end of this piece. The ideal omega-6 to omega-3 ratio is generally agreed to be 4 to 1. That’s four times the omega-6 as omega-3. How come?  The enzymes that desaturate and elongate fatty acids prefer to work along the n-3 pathway, and by the time they get to the n-6 fats, part of the n-6’s have been burned for energy. Also, the enzyme pathway could be interrupted by age, booze, trans-fats, disease and overdose of dietary cholesterol (which is a good thing that can be overdone).

If fish oil is held culpable, which form?  The ethyl ester form (EE) is made when the glycerol backbone of fish body oil is removed during molecular distillation and replaced by an ethanol, allowing the process to be completed at a lower temperature. It isn’t a fat any more, and really shouldn’t be allowed to be called an oil. This is now an ester that is not digested and absorbed by the body in the same manner as the original triglyceride. Once distilled, true fish oil has its triglyceride put back in a process called re-esterification, or re-concentration, a procedure that adds about 40% to the cost of the finished product. But this replacement of the glycerol—fish oil is a triglyceride—returns the substance to its natural state. Fish oil that has an alcohol head is metabolized just like an alcohol from liquor, and that’s not what we expect from a supplement that’s supposed to be a boon to health. Bioavailability of re-esterified triglycerides is superior to all other forms of fish oil (Dyerberg, 2010).

The study in question (Brasky, 2013) is of an observational nature, not experimental, such as a randomized, controlled, double-blinded trial would be.  Observational studies are not used as reliable sources, though they can help to formulate hypotheses to be used in subsequent experiments (Nahin, 2012). Additionally, cause-effect has not been established. The paper was quick to point the finger at a dietary supplement. True, many supplements are misused for lack of direction by a qualified health care practitioner, such as a dietitian or clinical nutritionist. But that can be resolved with a phone call and an appointment. Mega-doses of fish oil do not mix well with drugs or supplements that thin the blood. If a person doesn’t know that, he needs to. Though there is no established upper limit for fish oil, six grams might be too much, while two or three grams might just be on the mark for most adults. Actual dosage depends on the fish species and the levels of EPA and DHA in the product.

To balance the omega-3 fatty acids, evening primrose oil (EPO) is a good source of omega-6 fats, particularly of gamma-linolenic acid (GLA), which is the preferred launching point for conversion to the longer derivatives. Yes, borage oil has more GLA than EPO, but also contains alkaloids that can tax the liver.

An interesting comment from the University of Guelph in Ontario, Canada is, “I have no idea how this paper got accepted for publication.”  (Professor Gopinadhan Paliyath)

Refere

References

Akinsete JA, Ion G, Witte TR, Hardman WE.
Consumption of high ω-3 fatty acid diet suppressed prostate tumorigenesis in C3(1) Tag mice.
Carcinogenesis. 2012 Jan;33(1):140-8.

Astorg P.
Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence.
Cancer Causes Control. 2004 May;15(4):367-86.

Beckermann B, Beneke M, Seitz I.
Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers.
Arzneimittelforschung. 1990 Jun;40(6):700-4.

Bianchini F, Giannoni E, Serni S, Chiarugi P, Calorini L.
22 : 6n-3 DHA inhibits differentiation of prostate fibroblasts into myofibroblasts and tumorigenesis.
Br J Nutr. 2012 Dec 28;108(12):2129-37

Brasky TM, Crowe FL, Kristal AR.
n-3 Fatty acids and prostate cancer risk.
Br J Nutr. 2012 Nov 14;108(9):1721.

Theodore M. Brasky, Amy K. Darke, Xiaoling Song, Catherine M. Tangen, Phyllis J. Goodman, et al
Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial
JNCI J Natl Cancer Inst (2013) doi: 10.1093/jnci/djt174 First published online: July 10, 2013

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.

Chua ME, Sio MC, Sorongon MC, Morales ML Jr.
The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: A meta-analysis.
Can Urol Assoc J. 2013 May;7(5-6):E333-43.

Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB.
Bioavailability of marine n-3 fatty acid formulations.
Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3):137-41.

Epstein MM, Kasperzyk JL, Mucci LA, Giovannucci E, Price A, Wolk A, Håkansson N, Fall K, Andersson SO, Andrén O
Dietary fatty acid intake and prostate cancer survival in Örebro County, Sweden.
Am J Epidemiol. 2012 Aug 1;176(3):240-52.

Fradet V, Cheng I, Casey G, Witte JS.
Dietary omega-3 fatty acids, cyclooxygenase-2 genetic variation, and aggressive prostate cancer risk.
Clin Cancer Res. 2009 Apr 1;15(7):2559-66.

Edward Giovannucci, Eric B. Rimm, Graham A. Colditz, Meir J. Stampfer, Alberto Ascherio,
Chris C. Chute and Walter C. Willett
A Prospective Study of Dietary Fat and Risk of Prostate Cancer
JNCI J Natl Cancer Inst. Volume 85, Issue 19; Pp. 1571-1579.

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.

Richard Nahin, PhD, MPH
Observational Studies and Secondary Data Analyses to Assess Outcomes in Complementary and Integrative Health Care
NCCAM Research Blog. 25 June, 2012

Neubronner J, Schuchardt JP, Kressel G, Merkel M, von Schacky C, Hahn A.
Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.
Eur J Clin Nutr. 2011 Feb;65(2):247-54.

Pettersson A, Kasperzyk JL, Kenfield SA, Richman EL, Chan JM, Willett WC, Stampfer MJ, Mucci LA, Giovannucci EL.
Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death.
Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):428-36.

Ivonne Ramírez-Silva, Salvador Villalpando, Jessica E Moreno-Saracho and Daniel Bernal-Medina
Fatty acids intake in the Mexican population. Results of the National Nutrition Survey 2006
Nutrition & Metabolism 2011, 8:33

Reese AC, Fradet V, Witte JS.
Omega-3 fatty acids, genetic variants in COX-2 and prostate cancer.
J Nutrigenet Nutrigenomics. 2009;2(3):149-58.

Schuchardt JP, Neubronner J, Kressel G, Merkel M, von Schacky C, Hahn A.
Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial.
Prostaglandins Leukot Essent Fatty Acids. 2011 Dec;85(6):381-6.

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)

Sorongon-Legaspi MK, Chua M, Sio MC, Morales M Jr.
Blood level omega-3 Fatty acids as risk determinant molecular biomarker for prostate cancer.
Prostate Cancer. 2013;2013:875615.

Szymanski KM, Wheeler DC, Mucci LA.
Fish consumption and prostate cancer risk: a review and meta-analysis.
Am J Clin Nutr. 2010 Nov;92(5):1223-33.

Torfadottir JE, Steingrimsdottir L, Mucci L, Aspelund T, Kasperzyk JL, Olafsson O, Fall K, et al
Milk intake in early life and risk of advanced prostate cancer.
Am J Epidemiol. 2012 Jan 15;175(2):144-53. .

Torfadottir JE, Valdimarsdottir UA, Mucci L, Stampfer M, Kasperzyk JL, Fall K, Tryggvadottir L et al
Rye bread consumption in early life and reduced risk of advanced prostate cancer.
Cancer Causes Control. 2012 Jun;23(6):941-50.

Torfadottir JE, Valdimarsdottir UA, Mucci LA, Kasperzyk JL, Fall K, Tryggvadottir L, et al
Consumption of fish products across the lifespan and prostate cancer risk.
PLoS One. 2013 Apr 17;8(4):e59799.

P.J. van Jaarsveld, C.M. Smuts, H.Y. Tichelaar, M. Kruger, C.J. Lombard, A.J.S. Benadé
The influence of different ratios and dosages of an ω6:ω3 fatty acid supplement on the lipoprotein cholesterol and fatty acid profile in nonhuman primates on a western atherogenic diet
Nutrition Research. 17(11-12); Nov-Dec 1997: 1733-1747

Vasuki Wijendran and K.C. Hayes
DIETARY n-6 AND n-3 FATTY ACID BALANCE AND CARDIOVASCULAR HEALTH
Annual Review of Nutrition. July 2004; 24: 597-615

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.

*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.
Active rheumatoid arthritis: effect of dietary supplementation with omega-3 oils. A controlled double-blind trial.
Rev Med Chil. 1991 Mar;119(3):267-72.

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.
Scand J Rheumatol. 1985;14(2):97-101.
Tarp U.
Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis.
Dan Med Bull. 1994 Jun;41(3):264-74.

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.

Neuro-Transmission In Overdrive?

neuro-transmittersIf ever there was a commonality among the senior crowd, lack of sound sleep is a top contender. An enigma of the twenty-first century—based on hustle and bustle, multiple job and social obligations, and harried family life—is that the definition of senior now includes fifty-year-olds. Some people contend that fifty is the new thirty; others hold that it’s the new seventy, largely based on inflammatory markers not visible from the outside. Looks like both ends are meeting in the middle, eh? Sleep, or rather the lack of it, seems not to have been much of an issue in the 50’s and 60’s. If getting there is half the fun of a journey, it’s doubly so with sleep. The problem is that it sometimes takes too long to reach the realm of Morpheus.

To encourage sleep there are things to do and not to do. Depending on your personal guru, some to-do’s might include getting comfortable, adjusting room temperature to the mid-sixties (Onen, 1994), picking the right position and wearing loose night clothes. If you happen to be one of those adults afraid of total darkness, use a night light if the moon has too few lumens, but keep it in the hallway. Go for the glow, not the glare. If you’re of the opposite persuasion, try a mask. In either case, be happy you don’t live in Alaska. If you need music, use it. White noise can be helpful, too. If your partner is bothered by your needs, move.

Tense muscles will keep you awake. So will pondering the exciting events of the day. Tensing and then relaxing muscles, working from bottom to top, while focusing on a muscle group, can help you to sink into the mattress until you feel ready to get into your desired position. The head and torso are somewhat stubborn, which explains why you start at the bottom. If it’s hard to get rid of the day’s stimuli, picture items and events as being black, considered the most tiresome color. A brand new black Porsche, on the other hand, might undo all this effort. You could try breathing exercises, guided imaginations, thinking of relaxing activities like fishing or woodworking, or even getting out of bed and watching a dull movie or reading.

Eating a carbohydrate snack or a protein that contains tryptophan might make you sleepy. Taking a magnesium supplement (Abassi, 2012) or an herbal such as valerian has been helpful in some instances (Salter, 2010). Chemicals are the last resort—after the lighting and temperature have been adjusted, after the aromatherapy has proven ineffective, and after everything else.

Some things you don’t want to do before bed include exercising, eating a sizeable feast, and drinking coffee or alcohol. Smoking also interrupts the drowse. And taking a fish oil supplement could amp your rpm’s past the red line. What’s that?? Is my high DHA fish oil keeping me awake?  Yes, it is because it’s out of balance with EPA. While it’s true that DHA is needed by the brain and retina to stay at optimal function, like the gas tank in your car, once filled, you can turn off the pump. It appears that DHA stimulates brain neurons by impinging on receptors that react to the presence of glutamic acid, the non-essential amino acid abundant in the human body, most prominently in the brain, where it is the prime excitatory neurotransmitter. Glutamate receptors are implicated in excitotoxicity, a state linked to neurodegenerative diseases (Lau, 2010) (Heath, 2002) (Hynd, 2004).

There is more than one kind of glutamate receptor, but the one called NMDA-receptor is the trouble maker that opens calcium channels. Besides being found in bone, calcium is an electrolyte that turns things on and makes things happen. When these channels are kept open, calcium rushes into a cell and causes muscle contractions, excitation of neurons, and the release of hormones and neurotransmitters. This kind of physiological activity is exactly what you don’t need when you’re trying to go to sleep. DHA substantially potentiates the peak electrical activity of NMDA/glutamate receptors (Nishikawa, 1994).

The advancement of science has relied on the question, “why?”  There comes a point where there is no answer because that’s just the way it is. Why do two hydrogens and one oxygen atom make water instead of something spendable?  Long-term potentiation is initiated by the influence of DHA on NMDA/glutamate receptors. That’s just the way it is. At this time, magnesium offers a feasible blockade to the opening of the calcium channels. But you’d need lots of it. In the mean time, DHA is responsible for learning and memory. You don’t want to turn that off. You just want to tone it down at night.

NMDA is N-Methyl-D-aspartic acid, an amino acid derivative used to stimulate a receptor by mimicking glutamate, which is the normal visitor to that receptor. NMDA differs from glutamate in that it stimulates only the NMDA receptor, having no bearing on other glutamate receptors involved in synaptic transmissions. Sequestering NMDA/glutamate by avoiding high-DHA supplements prevents the opening of the calcium gates and the consequent stampede that disrupts sleep. That’s just the way it is.

References

Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B.
The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial.
J Res Med Sci. 2012 Dec;17(12):1161-9.

Bonin A, Khan NA.
Regulation of calcium signalling by docosahexaenoic acid in human T-cells. Implication of CRAC channels.
J Lipid Res. 2000 Feb;41(2):277-84.

Cao D, Kevala K, Kim J, Moon HS, Jun SB, Lovinger D, Kim HY.
Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function.
J Neurochem. 2009 Oct;111(2):510-21.

Connor S, Tenorio G, Clandinin MT, Sauvé Y.
DHA supplementation enhances high-frequency, stimulation-induced synaptic transmission in mouse hippocampus.
Appl Physiol Nutr Metab. 2012 Oct;37(5):880-7.

Hamano H, Nabekura J, Nishikawa M, Ogawa T
Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat.
J Neurophysiol. 1996 Mar;75(3):1264-70.

Heath PR, Shaw PJ.
Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis.
Muscle Nerve. 2002 Oct;26(4):438-58.

Hynd MR, Scott HL, Dodd PR.
Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease.
Neurochem Int. 2004 Oct;45(5):583-95.

Kathleen N. Kannass, John Colombo, and Susan E. Carlson
Maternal DHA levels and Toddler Free-Play Attention
Dev Neuropsychol. 2009; 34(2): 159–174.

Kauer JA, Malenka RC, Nicoll RA.
NMDA application potentiates synaptic transmission in the hippocampus.
Nature. 1988 Jul 21;334(6179):250-2.

Kim HY, Spector AA, Xiong ZM.
A synaptogenic amide N-docosahexaenoylethanolamide promotes hippocampal development.
Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):114-20.

Lau A, Tymianski M.
Glutamate receptors, neurotoxicity and neurodegeneration.
Pflugers Arch. 2010 Jul;460(2):525-42.

Miller B, Sarantis M, Traynelis SF, Attwell D.
Potentiation of NMDA receptor currents by arachidonic acid.
Nature. 1992 Feb 20;355(6362):722-5.

Nabekura J, Noguchi K, Witt MR, Nielsen M, Akaike N.
Functional modulation of human recombinant gamma-aminobutyric acid type A receptor by docosahexaenoic acid.
J Biol Chem. 1998 May 1;273(18):11056-61.

Nishikawa M, Kimura S, Akaike N.
Facilitatory effect of docosahexaenoic acid on N-methyl-D-aspartate response in pyramidal neurones of rat cerebral cortex.
J Physiol. 1994 Feb 15;475(1):83-93.

Onen SH, Onen F, Bailly D, Parquet P.
Prevention and treatment of sleep disorders through regulation] of sleeping habits
Presse Med. 1994 Mar 12;23(10):485-9.

Nina L. Salazar-Weber and Jeffrey P. Smith
Copper Inhibits NMDA Receptor-Independent LTP and Modulates the Paired-Pulse Ratio after LTP in Mouse Hippocampal Slices
International Journal of Alzheimer’s Disease Volume 2011 (2011), Article ID 864753, 10 pages.

Salter S, Brownie S.
Treating primary insomnia – the efficacy of valerian and hops.
Aust Fam Physician. 2010 Jun;39(6):433-7.

Saugstad LF.
A “new-old” way of thinking about brain disorder, cerebral excitability–the fundamental property of nervous tissue.
Med Hypotheses. 2005;64(1):142-50.

Michelle L. Schlief, Ann Marie Craig, Jonathan D. Gitlin
NMDA Receptor Activation Mediates Copper Homeostasis in Hippocampal Neurons
The Journal of Neuroscience, January 5, 2005. 25(1):239–246-239

Schlief ML, Gitlin JD.
Copper homeostasis in the CNS: a novel link between the NMDA receptor and copper homeostasis in the hippocampus.
Mol Neurobiol. 2006 Apr;33(2):81-90.

Vlachová V, Zemková H, Vyklický L Jr.
Copper modulation of NMDA responses in mouse and rat cultured hippocampal neurons.
Eur J Neurosci. 1996 Nov;8(11):2257-64.

Wurtman RJ, Cansev M, Ulus IH.
Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides.
J Nutr Health Aging. 2009 Mar;13(3):189-97.

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

Blood Pressure and…

bloodpressure-cuffThere is no naturally normal value for blood pressure (BP), but if yours is higher than that level deemed risky, you need to do something about it or face the possibility of some nasty consequences, such as stroke or cardiac episode, both of which can kill you—and are preventable. During each beat of the heart, pressure varies between a maximum, called systolic, and a minimum, called diastolic. The systolic pressure is the force that pushes blood out of the left ventricle; diastolic pressure refers to the heart at rest. The word diastole means dilation.

High blood pressure can cause arteries to become harder and thicker. Sometimes that can cause a bulge, an aneurysm, a weak spot in the artery that is subject to rupture, resulting in hemorrhage and probably death. Aneurysms don’t disappear by themselves, so some kind of invasive procedure might follow, depending on size and location. Copper deficiency is associated with aneurysm risk, so you might want to look at your diet, particularly if it’s high in zinc, the element some believe will improve male health and performance. But assuring copper sufficiency won’t necessarily prevent an aneurysm caused by elevated BP.

If the heart has to work harder to pump blood against the elevated pressures in the vessels, the heart muscle can get thicker, which makes it even more difficult to pump blood. This is the onset of heart failure, which may or may not be easily treated. In fortunate instances, a thickened heart can revert to normal size. Effects of continued high BP may involve the kidneys, brain and eyes. In polls, most people would rather die than face blindness (Giridhar, 2002) (Pfizer, 2008), which can result from hypertensive retinopathy.

There is no known cause of essential hypertension, but risks have been identified to include salt intake, obesity, race, physical activity, stress, heredity and diet. Secondary hypertension may be related to kidney, endocrine or neurological dysfunction. Medications, such as amphetamines and decongestants, can elevate blood pressure, as can alcohol. What is termed “normal” BP is a systolic pressure less than 120 mmHg and a diastolic pressure less than 80 mmHg (120/80). It takes a visit with your physician to determine your personal baseline and to work out a protocol if one is deemed necessary. That might include a medication besides a dietary intervention to address overweight.

Because cardiovascular disease is a leading cause of mortality in the economically developed world, much attention has been given to it. Diet and lifestyle are significant influences on cardiac risk, and may instigate abnormal lipid profiles, insulin resistance, diabetes and other pathologies suggestive of their impact. Of interest in the management of CVD risk factors are omega-3 fatty acids. Both omega-3 and omega-6 fats are considered essential; the body is unable to synthesize them. The conversion of the mother omega-3 and omega-6 fats, alpha-linolenic acid and linoleic acid, to longer-chain fatty acids, EPA/DHA and arachidonic acid, is terribly inefficient. Because omega-6 fats are held to be a dietary excess by virtue of a regimen high in processed foods and cheap supermarket oils, omega-3 fats, as fish oil, have received considerable interest. Fish oil is rich in EPA and DHA, the former having cardiovascular attributes and the latter having cerebral and retinal activity. Together, these fatty acids have induced moderate reductions in blood pressure at doses approximating 3 grams a day in both treated and untreated persons with elevated BP (Abeywardena, 2011). The mechanism explaining the activity is uncertain, but appears related to improvement in vascular endothelial function, one of these being reduction in stiffness. To address concerns about fish oil’s effect on LDL cholesterol, it is noted that the change in LDL particle size from small to large is a benefit (Ibid.).

One characteristic of hypertension is thickening of the arterial wall. In an animal model of hypertension, arterial thickening was attenuated with DHA treatment and the blood pressure decrease was compared to that induced by a beta blocker. Though only conjectural, other mechanisms by which fish oil lowers BP may involve activation of potassium channels (Toshinori, 2013). It is also possible that the anti-inflammatory compounds encouraged by fish oils ameliorate BP through a hormone-like effect that works in conjunction with the fatty acids’ blood-thinning character. Doses here approach 3 grams a day (Cabo, 2012).

In a twelve-week comparison/contrast trial pitting the omega-6 safflower oil against fish oil, the latter was found to offer significant benefit in reducing blood pressure in subjects with mild hypertension (Radack, 1991), while introducing no adverse changes in plasma lipid values. Including this with sixty-nine other random trials, researchers agree that available evidence indicates that inclusion of EPA/DHA in one’s diet reduces both systolic and diastolic BP at doses of at least 2 grams a day (Miller, 2014). Joining a fish oil protocol with a weight loss program, where applicable, wrought a 13 point drop in systolic and a 9 point drop in diastolic numbers in a cohort having a body mass index in excess of 31.0, the point at which obesity is defined (Bao, 1998).

If you take a prescription medication to keep your blood pressure controlled, don’t just stop it in favor of the fatty acids in fish oil. Doing so risks damage from BP rebound, which can cause serious damage to an artery. If you experience unwelcome side effects from your meds, talk with the doctor and look for an alternative drug. There certainly are enough of them on the market. Integrating fish oil with a BP drug is not generally a hazard, and may even be a boon. On the other hand, if BP falls too low, you can get dizzy, especially after standing from a sitting position. Essential fatty acids exist in the realm of complementary medicine, which is meant to complement, not necessarily to replace, conventional modalities in treating a variety of physical maladies. Hypertension is one that is relatively easy to manage.

References

Abeywardena MY, Patten GS.
Role of ω3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors.
Endocr Metab Immune Disord Drug Targets. 2011 Sep 1;11(3):232-46.

Bao DQ, Mori TA, Burke V, Puddey IB, Beilin LJ.
Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives.
Hypertension. 1998 Oct;32(4):710-7.

Biermann J, Herrmann W.
Modification of selected lipoproteins and blood pressure by different dosages of n-3-fatty acids.
Z Gesamte Inn Med. 1990 Sep 15;45(18):540-4.

Borghi C, Cicero AF.
Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management.
Heart Int. 2006;2(2):98.

Cabo J, Alonso R, Mata P.
Omega-3 fatty acids and blood pressure.
Br J Nutr. 2012 Jun;107 Suppl 2:S195-200.

Cicero AF, Ertek S, Borghi C.
Omega-3 polyunsaturated fatty acids: their potential role in blood pressure prevention and management.
Curr Vasc Pharmacol. 2009 Jul;7(3):330-7.

Margolin G, Huster G, Glueck CJ, Speirs J, Vandegrift J, Illig E, Wu J, Streicher P, Tracy T.
Blood pressure lowering in elderly subjects: a double-blind crossover study of omega-3 and omega-6 fatty acids.
Am J Clin Nutr. 1991 Feb;53(2):562-72.

Miller PE, Van Elswyk M2, Alexander DD3.
Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.
Am J Hypertens. 2014 Jul;27(7):885-96.

Mori TA.
Omega-3 fatty acids and blood pressure.
Cell Mol Biol (Noisy-le-grand). 2010 Feb 25;56(1):83-92.

Morris MC, Taylor JO, Stampfer MJ, Rosner B, Sacks FM.
The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial.
Am J Clin Nutr. 1993 Jan;57(1):59-64.

Radack K, Deck C, Huster G.
Arch Intern Med. 1991 Jun;151(6):1173-80.
The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects. A randomized controlled trial.

Toshinori Hoshia, Bianka Wissuwab, Yutao Tiana, Nobuyoshi Tajimaa, Rong Xua, Michael Bauerb, Stefan H. Heinemannc, and Shangwei Houd
Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels
PNAS March 4, 2013. Published online before print March 4, 2013

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

Understanding the Highs and Lows of Triglycerides

Triglycerides-choiceYou have triglycerides. So do we. Sometimes a lot, sometimes not, sometimes too many. They’re formed by combining glycerol with three molecules of fatty acid, which can be the same or different. Glycerol is a sugar alcohol that provides the backbone of many lipids. It’s an important intermediate in carbohydrate and fat metabolism. High levels of triglycerides have been linked to atherosclerosis and heart disease. They’re the natural molecular form that makes up virtually all fats and oils in both plants and animals. Most of us know our cholesterol levels, and we even know about the differences between HDL and LDL. But managing triglycerides (TG’s) is just as important to cardiac health. About a third of U.S. adults have borderline TG levels, between 150 and 199 milligrams per deciliter. Many of those with high TG’s are older whites who smoke, are overweight, and who get less than 150 minutes of exercise a week. Women have a lower risk than men, and blacks and Mexican Americans have even lower risks (Ford, 2009).

The body makes TG’s from carbohydrates and sends them to fat cells where they’re stored for energy. High TG levels often accompany low HDL, in a kind of lipid profile that may run in families. HDL cholesterol between 40 and 60 milligrams per deciliter, and LDL less than 100 are reasonable goals. Where TG’s store unused calories and provide energy, cholesterol is used to build cells and to make some hormones. Really high TG’s can be a sign that something else is amiss, like high blood pressure or high blood glucose. Low thyroid hormones, liver or kidney conditions, and some genetic missteps can affect how the body converts fat to energy, so TG readings will be elevated. But beta blockers taken for high blood pressure, some diuretics, steroids and birth control pills can raise TG levels, too.

Lifestyle changes are the first line of defense against high TG’s. Losing weight, cutting calories and avoiding excess sugars and refined foods are simple steps, although weight loss may initially be a challenge. It takes only a few pounds to make a difference, and light exercise and alcohol avoidance can help. But there is a supplement that can rescue high TG’s—fish oil. Of course, when Big Pharma realized this, they had to make a prescription form—Lovaza, Glaxo Smith-Kline’s omega-3 prescription. What makes it different from plain fish oil is the FDA’s blessing, which states that Lovaza is the only omega-3 medication so approved. No other fish oil product may be called a medication. The same effect, though, can be realized by taking multiple capsules of OTC product. But because one’s prescription plan pays for Lovaza, it’s cheaper for the patient…and GSK makes a ton of money.

Fish oil contains EPA and DHA, fatty acids that benefit the cardiovascular system and the eyes and brain, respectively. The fatty acids from fish oils are anti-inflammatory and anti-thrombotic; they compete successfully with substances that cause platelet aggregation and vasoconstriction. In hypertriglyceridemia, fish oil decreases the secretion of very low density lipoproteins (VLDL), increases VLDL clearance and reduces TG transport (Nestel, 2000) (Stark, 2000). It is held that fish oil can influence CVD risk factors to such an extent as to reduce risk of coronary heart disease by as much as twenty-seven percent (Stark, 2000).

Some products labeled as fish oil are not really oils at all, but rather alternate lipids known as fatty acid ethyl esters, differing from authentic fish oil triglycerides. Because free fatty acids are rapidly oxidized, the TG structure offers greater stability to the fatty acids and prevents breakdown and oxidation (Segura, 1988). Ethyl esters are derived from the reaction of free fatty acids with ethanol. Here, the glycerol backbone of the TG is removed and substituted with alcohol (Mogelson, 1984). The resulting ester allows for fractional distillation of the long-chain fatty acids at lower temperatures. At this point, the EPA and DHA can be manipulated to levels greater than those found in the fish (Saghir, 1997). Ethyl esters (EE’s) are uncommon in nature, so are not properly digested and absorbed by the body. The process can be reversed by using food grade enzymes, restoring the product to its rightful TG form with the glycerol backbone. Doing this is not common to the industry because of the cost. The fatty acid-ethanol bond is about fifty times more resistant to digestive enzymes (pancreatic lipase) as compared to the triglyceride form (Yang, 1990) (Yang, 1990). TG fish oil yields fifty percent more plasma EPA/DHA after absorption than the EE form (Beckerman, 1990) (Dyerberg, 2010). Over the long term, however, EE absorption seems to equal out after a few months’ intake (Sadovsky, 2009). It is conjectured that the slower activity of EE fish oil results in sustained inhibition of sodium and calcium channels, helping to prevent arrhythmia (Leaf, 2003) (Lavie, 2009).

There is no discernible health risk to EE fish oil, not even for a person sensitiveto alcohol. There are stories about EE being able to melt polystyrene. Alcoholand water are polar substances, having different electrical charges at oppositeends. They do not react with non-polar materials, such as Styrofoam. So, if you’veever heard that EE fish oil will dissolve a Styrofoam cup, dismiss the thought.When it comes to oxidation, though, EE will oxidize faster than the TG fish oil,making it less reliable (Song, 1997). The TG fish oil is naturally occurringand less likely to go rancid. Doubtless there are myriad studies to support andnegate the efficacy of each form, but if either one lowers your triglyceridelevels, there’s no debate.

References

Ackman RG.
The absorption of fish oils and concentrates.
Lipids 27:858-62, 1992.

Bays HE, et al.
Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications.
Expert Rev Cardiovasc Ther. 2008;  6:391-409

Bays H:
Rationale for prescription omega-3-acid ethyl ester therapy for hypertriglyceridemia: a primer for clinicians.
Drugs Today (Barc). 2008;  44:205-246

Breslow, JL.
Review: n-3 Fatty acids and cardiovascular disease.
Am J Clin Nutr. 2006;  83(s):1477s-82s

Beckermann B, Beneke M, Seitz I.
Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers.
Arzneimittelforschung. 1990 Jun;40(6):700-4.

Best CA, Laposata M.
Fatty acid ethyl esters: toxic non-oxidative metabolites of ethanol and markers of ethanol intake.
Front Biosci. 2003; 8: 202-17.

Breslow JL.
N-3 fatty acids and cardiovascular disease.
Am J Clin Nutr ;83(6 Suppl):1477S-1482S, 2006.

Carlier H., Bernard A, Caseli A.
Digestion and absorption of polyunsaturated fatty acids.
Reprod Nutr Dev.(1991). 31: 475-500.

J Dyerberg , P Madsen , JM Moller ,I Aardestrup ,EB Schmidt.
Bioavailability of marine n-3 fatty acid formations.
Prostaglandins Leutkot. Essent. Fatty Acids. 2010; 83 137-141.

El Boustani S, Colette C, Monnier L, Descomps B, Crastes de Paulet A, Mendy F.
Enteral absorption in man of eicosapentaenoic acid in different chemical forms.
Lipids. 1987; 10: 711-714.

Eritsland J, Arnesen H, Seljeflot I, Høstmark AT.
Long-term metabolic effects of n-3 polyunsaturated fatty acids in patients with coronary artery disease.
Am J Clin Nutr. 1995 Apr;61(4):831-6.

Fave G, Coste TC and Armand M.
Physicochemical properties of lipids: New strategies to manage fatty acid bioavailability.
Cellular and Molecular BiologyTM. 2004; 50 (7), 815-831

Finnegan YE, Minihane AM, Leigh-Firbank EC, Kew S, Meijer GW, Muggli R, Calder PC, Williams CM.
Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects.
Am J Clin Nutr. 2003 Apr;77(4):783-95.

Earl S. Ford, MD, MPH; Chaoyang Li, MD, PhD; Guixiang Zhao, MD, PhD; William S. Pearson, PhD; Ali H. Mokdad, PhD
Hypertriglyceridemia and Its Pharmacologic Treatment Among US Adults FREE
Arch Intern Med. 2009;169(6):572-578.

GISSI-Prevenzione.
Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction.
Lancet 354:447-55, 1999.

Habber TS., Wilson JS, Minoti VA, Pirola RC.
Fatty acid ethyl esters increase rat pancreatic lysosomal fragility.
J. Lab. Clin. Med. 1991; 121:75-764

Hansen JB, Olsen JO, Wilsgård L, Lyngmo V, Svensson B.
Comparative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on lipids, homeostasis and platelet function in normolipaemic men.
Eur J Clin Nutr; 1993; ,47: 497-507.

Hansen JB, Berge RK, et al.
Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids.
Lipids. 1998;  33:1129-9

Harris WS, Zucker ML, Dujovne CA.
Omega-3 fatty acids in hypertriglyceridemic patients: triglycerides vs methyl esters.
Am J Clin Nutr; 1988; 48: 992-997

Ikeda I, Sasaki E, Yasunami H, Nomiyama S, Nakayama M, Sugano M, Imaizumi K, Yazawa K. Digestion and lymphatic transport of eicosapentaenoic and docosahexaenoic acids given in the form of triacylglycerol, free acid and ethyl ester in rats.
Biochim Biophys Acta. 1995; 1259: 297-304.

Krokan HE, Bjerve KS, Mørk E.
The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta; 1993;  1168: 59-67.

Lambert MS, Botham KM, Mayes PA. .
Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants.
Br J Nutr. 199.;76:435-45

Lange, L. G., and B. E. Sobel.
Mitochondrial dysfunction induced by fatty acid ethyl esters, myocardial metabolites of ethanol.
J. Clin. Invest. 1983; 72: 724-731,1983.

Laposata EA, Lange LG.
Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse.
Science;1986; 231: 497–9.

Lavie CJ et al.
Omega-3 polyunsaturated fatty acids and cardiovascular disease.
J Am Coll Cardiol. 2009; 51:585-94

Lawson LD, Hughes BG.
Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters.
Biochem Biophys Res Commun, 1988; 52, 328-335.

Leaf A, et al.
Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils.
Circulation. 2003; 107:2646-52

Lee JH, O’Keefe JH, Lavie CJ, Marchioli R, Harris WS.
Omega-3 fatty acids for cardioprotection.
Mayo Clin Proc 83(3):324-32, 2008.

Mogelson S, Pieper SJ, Lange LG. .
Thermodynamic bases for fatty acid ethyl ester synthase catalyzed esterification of free fatty acid with ethanol and accumulation of fatty acid ethyl esters.
Biochemistry. 1984 Aug 28;23(18):4082-7.

Montori VM, Farmer A, Wollan PC, Dinneen SF.
Fish oil supplementation in type 2 diabetes: a quantitative systematic review.
Diabetes Care. 2000 Sep;23(9):1407-15.

Nestel PJ.
Fish oil and cardiovascular disease: lipids and arterial function.
Am J Clin Nutr. 2000 Jan;71(1 Suppl):228S-31S.

J Neubronner , JP Schuchardt, G Kressel, M Merkel, C von Schacky and A Hahn.
Enhanced increase of omega-3 index in response to long term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.
Eur. J. of Clin. Nutr.(2010),1-8.

Nordøy A, Barstad L, Connor WE, Hatcher L.
Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans.
Am J Clin Nutr. 1991;  53:1185-90.

Patti L, Maffettone A, Iovine C, Marino LD, Annuzzi G, Riccardi G, Rivellese AA.
Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia.
Atherosclerosis. 1999 Oct;146(2):361-7.

Reis GJ, et al.
Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease.
Am J Cardiol 66:1171-75, 1990.

Rupp H.
Omacor (prescription omega-3-acid ethyl esters 90): From severe rhythm disorders to hypertriglyceridemia.
Adv Ther. 2009; 26:675-90,

Sadovsky R, et al.
Prescription omega-3 acid ethyl esters for the treatment of very high triglycerides.
Postgrad Med 121:145-153, 2009.

Saghir M, Werner J, Laposata M.
Rapid in vivo hydrolysis of fatty acid ethyl esters, toxic nonoxidative ethanol metabolites.
Am J Physiol. 1997; 273:G184-90.

Segura R.
Preparation of fatty acid methyl esters by direct transesterification of lipids with aluminum chloride-methanol.
J Chromatogr. 1988:;441:99-113.

Shearer GC, Savinova OV, Harris WS.
Fish oil — how does it reduce plasma triglycerides?
Biochim Biophys Acta. 2012 May;1821(5):843-51.

Song JH, Inoue Y, Miyazawa T.
Oxidative stability of docosahexaenoic acid-containing oils in the form of phospholipids, triacylglycerols, and ethyl esters.
Biosci Biotechnol Biochem.1997;  61(12):2085-8

Stark KD, Park EJ, Maines VA, Holub BJ.
Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double-blind trial.
Am J Clin Nutr. 2000 Aug;72(2):389-94.

Szczepiorkowski, Z. RI., G. R. Dickersin, and M. Laposata.
Fatty acid ethyl esters decrease human hepatoblastoma cell proliferation and protein synthesis. GastroenteroZogy. 1995; 108: 515- 522.

Villani AM, Crotty M, Cleland LG, James MJ, Fraser RJ, Cobiac L, Miller MD.
Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature.
BMC Geriatr. 2013 May 1;13(1):41.

Visioli F, Rise P, Barassi MC, Marangoni F, Galli C.
Dietary intake of fish vs. formulations leads to higher plasma concentrations of n-3 fatty acids.
Lipids. 2003; 38: 415-418.

Werner J, Laposata M, Fernandez-del Castillo C, Saghir M, Iozzo RV, Lewandrowski KB, Warshaw AL. Pancreatic injury in rats induced by fatty acid ethyl ester, a nonoxidative metabolite of alcohol.
Gastroenterology; 1997; 113: 286–94.

Yang LY, Kuksis A, Myher JJ.
Lipolysis of menhaden oil triacylglycerols and the corresponding fatty acid alkyl esters by pancreatic lipase in vitro: a reexamination.
J Lipid Res. 1990; 31(1):137-47.

Yang LY, Kukis A, Myher JJ.
Intestinal absorption of menhaden and rapeseed and their fatty acid methyl and ethyl esters in the rat.
Biochem Cell Biol. 1990; 68:480-91

Yoshii H, Furuta T, Siga H, Moriyama S, Baba T, Maruyama K, Misawa Y, Hata N, Linko P.
Autoxidation kinetic analysis of docosahexaenoic acid ethyl ester and docosahexaenoic triglyceride with oxygen sensor.
Biosci Biotechnol Biochem. 2002; 66:749-753.

Yuan GJ, Zhou XR, Gong ZJ, Zhang P, Sun XM, Zheng SH.
Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury.
World J Gastroenterol, 2006; 12, 2375-2381.

Zuijdgeest van Leeuwen SD, et al.
Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions.
Br J Nutr. 1999; 82:481-8

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