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Aging and The Brain

coconut oil, fats oils, essential fatty acids

Our brains are 60% fat. In light of what we know of brain function and the essential fatty acids that are responsible, the term “fat-head” could now be a complement. Since our brains are in charge and require the right fats to run our thinking machinery, our first priority is to make sure we add the right ones into our diet, the omega 6s and omega 3s. They are essential and get the job done. First – let’s review some of the basics.

Fats and oils can be divided into two densities and two levels. The densities are not unlike the SAE oils, the Society of Automotive Engineers who organize the oils for our autos. But it is better to skip the details at the moment and divide them in two categories “thick” and “thin”. Fats are the thick ones and oils are thin, actually runny. It’s quite good to divide them in this simplistic way. The confusion about what we eventually eat is all over the lot and besides, our cells and membranes organize fats and oils as partners with each having a precise role. The membrane does not work without both, thick and thin, sluggish and active. We can begin with the ones we use in our kitchens because they wind up in our metabolism whether we like it or not.

You can think of the thick ones as butter or lard. We tend to look down on lard as being out of date. We regard it as a thing of the past. Our grandparents and great grandparents certainly didn’t think so. As cooking oil, lard has been with us for some time. It’s been a staple for centuries, probably hundreds of centuries, and we’ve survived and even flourished. It’s part of our evolutionary history. Those thick heavy oils were skimmed off the top of stews and saved, collected from roasts of pork, lamb, goose or turkey. It was regarded as valuable stuff. Before the light bulb, making candles was a basic part of life so the rendering of fat in the kitchen was universal. The plain fact is that lard is OK for cooking. However, just reminiscing, not pushing lard today.

Butter and olive oil are both excellent cooking oils, however, coconut is also marvelous for cooking. It’s not exactly a thick fat, for as you know, it quickly gets thin as the temperature rises. Castillo et al 1999, reports that “Supplementation of coconut oil produced a significant hypercholesterolemia after 7 days of treatment. However, supplementation of menhaden oil induced a significant decrease in total cholesterol after only 2 weeks of treatment”. The raising of cholesterol may sound sacrilegious; however, notwithstanding the loud din of media anti-cholesterol noise, there are those who have difficulty in doing just that – raising cholesterol. Cholesterol is an important fat for our cell membranes; it metabolizes up to our gonadal hormones — think sex. No necessity in elaborating on that subject. It’s also a precursor for our adrenal hormones, which produce our life saving impulses for fight or flight, and bile acids which shepherd the fats and oils around in the blood stream. Without further ado — cholesterol is necessary.

Castillo creates an interesting picture of coconut oil, or butter, as you prefer, and the essential oils that are part of our diet. By itself, coconut can raise cholesterol, but by introducing menhaden oil, it just as quickly reverses and lowers it. This feature of menhaden oil, basically an omega 3 essential fatty acid (EFAs), to lower cholesterol, is also duplicated with the omega 6 EFAs, and there is abundant research that corroborates it. We can regard all of the omega 6s and 3s as “thin oils” and cholesterol, when grouped together as a very “thick fat”.

The lesson here is more than casual. We need the thick ones and we desperately need the thin ones. The thin ones keep the thick ones from collecting to the degree where we tend to get into trouble that comes with aging, such as atherosclerosis, heart disease. In just these two words, thick and thin, we have covered half of all Fatty Acid biochemistry in human metabolism. But it may be just too simple to be looked at with the respect that it deserves. You may spend a third of your life getting a medical degree and half again practicing medicine, but if you do not see this simple relationship you will also retire as a failure from your chosen field of medicine.

Coconut used to be the preferred oil for making popcorn, but ADM and the other large oil producers chased it out of the movies over 30 years ago. It’s a shame we lost it. It was much healthier eating coconut oil than what is currently in use today. Most of the oils used for popcorn and fries are PUFAs, they are thin and should not be heated. They quickly degenerate and become partially hydrogenated and/or oxidize and become rancid.

Coconut oil is one of the most stable oils you can buy. It does not turn rancid easily. It does not attack your arteries. In fact, coconut oil was one of the foods Dr. Weston Price studied when he traveled the world searching for healthier people and their lifestyles. In his journeys he discovered that the coconut was considered a medicine food by the local populations. He found that those civilizations that consumed coconut regularly had no knowledge of cancer, heart disease, arthritis, or diabetes.

There are few other choices for cooking unless you think of the new GMO oils like high oleic soybean, sunflower or safflower oils, Canola also fits into that group because it was one of the first GMO oils to be converted. Canola contains erucic acid, a very long chain saturated fat. It is unhealthy for our membranes, it’s too long and slows the fluidity of the membrane. Think of erucic as a gawking fat blocking our healthy fats from doing what they want to do, running quickly in our membranes managing our cells. Please avoid canola. We simply do not like GMOs for anything we eat.

The thin oils, the PUFAs, come from seeds, nuts, and grains like olive, sunflower, corn, walnut, etc. They harbor the essential fatty acids which play a vital role when the time comes for them to reproduce new versions of themselves. Oils like olive are mostly Mono-Unsaturated Fatty Acids (MUFAs), and are OK, but do not stack up with the likes of the omega 6 and 3 PUFAs, the very healthy FAs. These Poly-Unsaturated Fatty Acids, with more than one double bond, are the stars in our choices of foods. They are predominantly made up of the essential oils, the omega 6s and the omega 3s and are exclusively made by plant seeds. They are important for life and especially the brain. When we use the term essential, we mean that the body cannot function without them. They are essential for life, our life. They hold the secret to Brain health, which we will delve into on Aging and the Brain: Part 2.

To learn more about one of the most important EFA discoveries of the last century, the ratio of 6s and 3s, which is 4: 1, 80% omega 6 (linoleic) to 20% omega 3 (linolenic), go tohttp://www.bodybio.com/BodyBio/docs/BodyBioBulletin-4to1Oil.pdf.

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

Longevity And Stress

hand-squeezing-stress-ballJust as oxidation causes iron to rust and brass to tarnish, it causes our cells to rust and tarnish, only figuratively and not literally…unless the Tin Man is part of the gene pool.  When you get stressed out—and there’s a litany of reasons for that—your body makes oxidative chemicals that hasten aging, increase cardiovascular risk, and set the stage for myriad chronic and acute illnesses, including relatively benign things like colds.

Vanderbilt University discovered that accurate and uncomplicated assessment of oxidative stress inside the body could be accomplished by the measurement of chemicals called isoprostanes.  These substances are derived from the action of free radicals on fatty acids, and can be found in plasma and urine.  Primarily associated with risk of atherosclerosis, isoprostanes levels are elevated by “cigarette smoking, hypercholesterolemia, diabetes mellitus, and obesity,” among other factors.  Additionally, “Enhanced oxidant stress occurring either locally in the vessel or systemically is implicated…in atherosclerosis in humans.”  (Morrow. 2005)   In circumstances not cardiac-related, isoprostanes are inflammatory mediators that augment the perception of pain.

As long as there is oxygen there will be oxidation, but most species have developed ways to deal with it.  What separates humans from other life forms is that we do things on purpose to increase the oxidative process.  We eat the wrong foods, we smoke, we are sedentary, and we worry about things that never happen, while fretting about things we cannot change.  We even worry about getting diseases that are not likely to attack us by virtue of genetic exclusion, but sometimes do get a start because we worried about them needlessly.  The body’s response to oxidative stress, which can be prompted by both mental and physical assaults, is tied to aging and life span.  (Finkel. 2000)

There is increasing evidence that psychosocial stress can cause system-wide derangement of cellular homeostasis, accompanied by heightened oxidative stress and pro-inflammatory activity.  (Marotta. 2011)  Persons under stress have elevated levels of malondialdehyde (MDA), a product that stems from the oxidation of fatty acids and that degrades the integrity of the cell.  This, in turn, can cause mutations of DNA.  That can initiate a plethora of unwelcome events.

Mental stress can incite physical responses, some of which may appear as gastrointestinal conditions, tension headaches, hypertension, irritable bowel syndrome, sexual dysfunction, alcoholism, fatigue, and skin conditions that include psoriasis, lichen planus, itching and hives.  Some or all of these may be related to increased cortisol production by the adrenal glands.  Stress can affect other hormones, as well, and is implicated in depression and impaired immune function.

Because the brain has high fatty acid content, it seems logical that fatty acids are involved in brain chemistry, physiology, and function.  Therefore, it follows that cognitive health and neuropsychiatric well-being are intertwined.  Omega-3 fatty acids, such as those from fatty fish and fish oil supplements, appear effective in the prevention of stress (and manufacture of cortisol) and in the regulation of mood.  (Perica. 2011)  In fact, the first consistent demonstration of the effect of dietary ingredients on the structure and function of the brain involved omega-3 fats.  (Bourre. 2005)

At the ends of our chromosomes are telomeres, pieces of DNA that are the equivalent of shoelace aglets (those plastic sheaths that help to thread the laces).  When telomeres start to fray because of continual cell replication, cells become senescent—they grow old.  Oxidative stress shortens telomeres, thus hastening aging and the onset of age-related diseases, none of which started yesterday.  (Epel. 2004)  If cortisol is one of the major hormones related to telomere shortening, then it is to our benefit to diminish it.  Stressors coming from outside the body are not so easy to handle.  But this does not mean that internalized stressors are more manageable.  Maintaining proper weight and controlling glucose are important stressors to consider.

The employment of functional foods and certain supplements can help to ease stress, to lighten the cortisol load, and to bolster immune defenses.  Telomeres may be preserved by a diet that reduces added sugars.  Essential fatty acids can ease the mental burdens of the daily grind.  Green tea polyphenols have shown to be effective in addressing a variety of oxidative, pro-inflammatory processes (Yang. 1998), while having a beneficial effect on nucleic acid and protein synthesis (Beltz. 2006).  The vitamin B complex is collectively known as the stress vitamins, and their utility as such has been reported often over past decades (Kennedy. 2011)  (Stough. 2011)  Intense Chinese research has discovered that telomeres may be rescued from senescence by epigallocatechin gallate (ECGC) in green tea, and by quercitin from apples, onions, citrus, and dark berries. (Sheng. 2011)

Stress-fighting, mood-lifting foods include such simple ingredients as oatmeal, pistachios, avocadoes, and wine.  Turkey, eggs, water, and almonds can affect your affect.  Chocolate can calm things by releasing endorphins, and walnuts can get rid of the blues by increasing uridine, which boosts communication among neurons.  Spinach helps maintain normal levels of serotonin, a mood enhancer that also deals with the sleep-wake cycle and pain perception.  If, on the other hand, you care little about stress and what it does to your body, go ahead and eat half a dozen bacon-fried doughnuts.

References

Morrow JD.
Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans.
Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86.

Finkel T, Holbrook NJ.
Oxidants, oxidative stress and the biology of ageing.
Nature. 2000 Nov 9;408(6809):239-47.

Marotta F, Naito Y, Padrini F, Xuewei X, Jain S, Soresi V, Zhou L, Catanzaro R, Zhong K, Polimeni A, Chui DH.
Redox balance signalling in occupational stress: modification by nutraceutical intervention.
J Biol Regul Homeost Agents. 2011 Apr-Jun;25(2):221-9.

Perica MM, Delas I.
Essential fatty acids and psychiatric disorders.
Nutr Clin Pract. 2011 Aug;26(4):409-25.

Bourre JM.
Dietary omega-3 Fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging
J Nutr Health Aging. 2005;9(1):31-8.

Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM.
Accelerated telomere shortening in response to life stress.
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5.

Yang F, de Villiers WJ, McClain CJ, Varilek GW.
Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model.
J Nutr. 1998 Dec;128(12):2334-40.

Beltz LA, Bayer DK, Moss AL, Simet IM
Mechanisms of cancer prevention by green and black tea polyphenols.
Anticancer Agents Med Chem. 2006 Sep;6(5):389-406.

Kennedy DO, Veasey RC, Watson AW, Dodd FL, Jones EK, Tiplady B, Haskell CF.
Vitamins and psychological functioning: a mobile phone assessment of the effects of a B vitamin complex, vitamin C and minerals on cognitive performance and subjective mood and energy.
Hum Psychopharmacol. 2011 Jul 12. doi: 10.1002/hup.1216.

Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA.
The effect of 90 day administration of a high dose vitamin B-complex on work stress.
Hum Psychopharmacol. 2011 Sep 8. doi: 10.1002/hup.1229.

Sheng R, Gu ZL, Xie ML
Epigallocatechin gallate, the major component of polyphenols in green tea, inhibits telomere attrition mediated cardiomyocyte apoptosis in cardiac hypertrophy.
Int J Cardiol. 2011 Oct 14.

Huk-Kolega H, Skibska B, Kleniewska P, Piechota A, Michalski Ł, Goraca A.
Role of lipoic acid in health and disease
Pol Merkur Lekarski. 2011 Sep;31(183):183-5.

Rios A, Delgado-Casado N, Cruz-Teno C, Yubero-Serrano EM, Tinahones F, Malagon MD, Perez-Jimenez F, Lopez-Miranda J.
Mediterranean diet reduces senescence-associated stress in endothelial cells.
Marin C, Delgado-Lista J, Ramirez R, Carracedo J, Caballero J, Perez-Martinez P, Gutierrez-Mariscal FM, Garcia-
Age (Dordr). 2011 Sep 6.

Lin J, Epel E, Blackburn E.
Telomeres and lifestyle factors: Roles in cellular aging.
Mutat Res. 2011 Aug 22.

Murillo-Ortiz B, Albarrán-Tamayo F, Arenas-Aranda D, Benítez-Bribiesca L, Malacara-Hernández J, Martínez-Garza S, Hernández-González M, Solorio S, Garay-Sevilla M, Mora-Villalpando C.
Telomere length and type 2 diabetes in males, a premature aging syndrome.
Aging Male. 2011 Aug 9.

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

Mighty Mitochondria… and Cardiolipin, Too

mitochondrion-cross-sectionMitochondria Are…

Suppose you were asked to name the most important part of your car?  Of course, without an engine you’re not going anywhere.  Without a transmission you’re not going anywhere, either.  So, which is it, the engine or the transmission?  Then, once you get moving, it’s nice to be able to stop.  Brakes, right?  Or perhaps you choose to steer around an obstacle.  Maybe there isn’t a most important part.  Ditto the cell, the unit of structure and function of living things, the smallest unit that can perform an essential life process.  Like your car, the cell has parts.  Considering that you have more than fifty trillion cells, the parts have to be tiny, really tiny.

Each cell is enclosed by a membrane that is made from proteins and a double layer of lipids.  The membrane is vital to the existence and function of the cell because it controls the flow of materials into and out of it, and it keeps the cell’s contents from spilling all over the place.  Not only does the cell have a membrane, but also do its components.  If we were to open and stretch out all the membranes of your body, they’d cover more than forty square miles.  But that’s nothing.  If we uncoiled all your strands of DNA and laid them end to end, they’d reach the sun and back more than once.  When the Psalmist said he was fearfully and wonderfully made, he didn’t realize how right he was.

A component of the cell that shares its architecture is the mitochondrion, sometimes referred to as the power plant of the cell because it makes most of the cell’s supply of adenosine triphosphate (ATP), used as a source of chemical energy.  Like the cell itself, the mitochondrion has an inner and an outer leaf to the membrane.  Mitochondria have other tasks besides making energy, including signaling, cell death, and control of the cell cycle. You already know that different cells have different jobs, each determined by what the nucleus says. Some cells do more work than others and require more energy.  Therefore, some have more mitochondria than others.  You would expect to find more mitochondria in a bicep than in the muscle that blinks an eye.  Each mitochondrion has an intermembrane space—found between the outer and inner membrane leaflets—that controls the movement of proteins. Small molecules have no problem crossing the outer membrane, but larger proteins need to be escorted by a specialized signaling sequence. (sorry about the alliteration)  A noted protein that is localized to the intermembrane area is called cytochrome c, the most abundant and stable cytochrome, principally involved in energy transfer.  Mitochondrial proteins vary depending on the tissue.  More than six hundred types have been identified in the human cardiac mitochondria, for example.  And, even though most of a cell’s DNA is in the nucleus, mitochondria have their own supply.

If there were no mitochondria, the higher animals could not exist.  Mitochondria perform aerobic respiration, requiring oxygen, which is the reason we breathe.  Without them we would have to rely on anaerobic respiration, without oxygen.  That process is too inefficient to support us.  Besides, the lack of mitochondria would reduce energy production by fifteen times, which is far too low to allow survival. A mitochondrion’s DNA reproduces independently of the cell in which it is found.  In humans, this DNA covers more than sixteen thousand base pairs, not very many compared to the whole organism.  Mitochondrial DNA holds thirty-seven genes, all of which are needed for normal function.  Thirteen of these supply information for making enzymes involved in oxidative phosphorylation, which is how ATP is made by using oxygen and simple sugars.  The other twenty-four genes help to make transfer RNA (tRNA) and ribosomal RNA (rRNA), which are chemically related to DNA.  These kinds of RNA are responsible for assembling amino acids into functioning proteins.

Mitochondria are passed on through maternal lineage.  Just as a car’s energy supply from gasoline is in the rear, so is a sperm’s mitochondrial energy—in the tail, which falls off after the sperm attaches to the egg.  This means that any problems, like mitochondrial diseases, necessarily come from the female.  Mitochondrial DNA (mtDNA) does not get shifted from generation to generation, while nuclear DNA does.  It is mtDNA that sends some diseases down the line.  mtDNA, though, is also subject to non-inherited mutations that cause diseases.  Fortunately, these are not passed on, but are accountable for various cancers, such as breast, colon, stomach and liver, diseases that have been attributed to reactive oxygen species.  mtDNA has limited capability to repair itself, so the inherited changes may cause problems with the body’s systems, where the mitochondria are unable to provide sufficient energy for cells to do their work.  The inherited consequences may present as muscle wasting, movement problems, diabetes, dementia, hearing loss, or a host of other maladies.

Some mitochondrial functions are performed only in specific cells.  In the liver, for example, they are able to detoxify ammonia, a job that need not be accomplished anywhere else in the body.  Other metabolic tasks of mitochondria include regulation of membrane potential, apoptosis, calcium signaling, steroid synthesis, and control of cellular metabolism.  You can see that mitochondria are vital to life, and their malfunction can change the rules.  In some mitochondrial dysfunctions there is an interaction of environmental and hereditary factors that causes disease.  Such may be the case with pesticides and the onset of Parkinson’s disease—cellular damage related to oxidative stress.  In other dysfunctions, there may be mutations of certain enzymes, such as coenzyme Q10 deficiency, or aberrations in the cardiolipin molecules that are found inside mitochondria, causative of Barth syndrome, which is often associated with cardiomyopathy.  Mitochondria-mediated oxidative stress may also play a role in Type 2 diabetes.  In cases where misconstrued fatty acid uptake by heart cells occurs, there is increased fatty acid oxidation, which upsets the electron transport chain, resulting in increased reactive oxygen species.  This deranges the mitochondria and elevates their oxygen consumption, resulting in augmentation of fatty acid oxidation.  Merely because oxygen consumption increases does not necessarily mean that more ATP will be manufactured, mostly because the mitochondria are uncoupled.  Less ATP ultimately causes energy deficit, accompanied by reduced cardiac efficiency.

Mitochondria can become involved in a vicious cycle of oxidative stress leading to mitochondrial DNA mutations, which leads to enzyme irregularities and more oxidative stress.  This may be a major factor in the aging process.

Rescue My Mitochondria, Please

The neurodegeneration of Parkinson’s disease is characterized by a loss of dopaminergic neurons and a deficit in mitochondrial respiration.  Exposure to some neurotoxins can present with both characteristics.  In a Parkinson’s model provoked by a drug that was produced to mimic the effects of morphine or meperidine (Demerol), but which interferes with oxidative phosphorylation in mitochondria instead, causing depletion of ATP and cell death, scientists at Columbia University’s Center for Neurobiology and Behavior found that the administration of ketone bodies akin to those used in the treatment of epilepsy were able to attenuate the dopaminergic neurodegeneration and motor deficits induced by the drug (Tieu, 2003).  From this and other studies it has been determined that ketones may play a therapeutic role in several forms of neurodegeneration related to mitochondrial dysfunction (Kashiwaya, 2000).

Moving across the mitochondrial membrane, phosphatidylcholine (PC) limits the phospholipid turnover in both the inner and outer leaflets that epitomizes the membrane defect identified in neurological diseases (Dolis, 1996), including Alzheimer’s, a disease in which impairment of mitochondrial function is part of the pathophysiology.  Substances that inhibit mitochondrial function also activate an enzyme called phospholipase A2 (PLA2) that degrades PC in the membrane (Farber, 2000), but reparation to mitochondria may be realized by administering PC liposomes, as evidenced by Russian studies performed in the early 1990s (Dobrynina, 1991).

Cardiolipin is an important component of the inner mitochondrial membrane, where it makes up about 20% of the lipid composition.  Its operational character is critical to the optimal function of numerous enzymes essential to mitochondrial energy metabolism.  Mitochondrial cardiolipin is distinguished from other phospholipids by the presence of linoleic acid derivatives (Schlame, 1990).  The formation of cardiolipin is dependent upon molecules donated by PC, but because it contains 18-carbon fatty alkyl chains with two unsaturated bonds, it bespeaks a linoleic acid heritage.   The need for linoleic acid, an omega-6 fat, was announced by the American Heart Association several years ago (Harris, 2009).

In the aforementioned Barth syndrome there exist cardiolipin abnormalities and resultant defects in the electron transport chain proteins and the architecture of the mitochondrion.   The electron transport chain (ETC) moves electrons from one cytochrome to another during the production of ATP, terminating at oxygen through a series of increasingly strong oxidative activities.  Those few electrons that fail to make it through the entire process leak and form superoxide, a substantially reactive molecule that contributes greatly to oxidative stress and aging.

Since the heart is rich in cardiolipin, it is more than appropriate to maintain its stores.  And linoleic acid is just the thing to do that.  Dutch researchers found that linoleic acid, readily available from sunflower, hemp, grape seed and other oils, restores and even increases cardiolipin levels (Valianpour, 2003).   Chronic over-consumption of omega-3 fats, such as those from fish oils, creates a deficit of omega-6 fats that interferes with the rate of oxygen use by mitochondria, with consequent decrease of cardiolipin (Yamaoka, 1999) (Hauff, 2006).

Coronary heart disease is a major health issue that may be addressed by supporting cardiolipin integrity, but other conditions likewise respond to such support.  Besides maintaining membrane potential and architecture, cardiolipin provides sustainment to several proteins involved in mitochondrial energy production.  If cardiolipin activity is interrupted or deranged, either through oxidative stress or alterations in acyl chain composition, we may anticipate contending with other pathological conditions, such as ischemia and hypothyroidism, and accelerated aging (Chicco, 2007).  These concerns can be allayed by attending to the status of the tafazzin protein that partly underlies cardiolipin metabolism (Xu, 2006).  Superheroes have long been associated with a sidekick, occasionally with role reversal for the nonce.  Working with linoleic acid to bolster cardiolipin is phosphatidylcholine (PC), which assists protein reconstitution by its ability to transfer acyl groups (Xu, 2003) (Schlame, 1991) and enhance protein signaling.  PC exists in every cell of the body, occupying the outer leaflet of the membrane.  Throughout the course of life, PC levels become depleted and may drop as low as 10% of the membrane in elderly people.  Being so, supplementation is warranted, not only to maintain cardiolipin levels and mitochondrial stability body-wide, but also to retard senescence and to improve brain function and memory capacity.

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Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues.
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Xu Y, Kelley RI, Blanck TJ, Schlame M.
Remodeling of cardiolipin by phospholipid transacylation.
J Biol Chem. 2003 Dec 19;278(51):51380-5. Epub 2003 Oct 9.

Xu Y, Malhotra A, Ren M, Schlame M.
The enzymatic function of tafazzin.
J Biol Chem. 2006 Dec 22;281(51):39217-24. Epub 2006 Nov 2.

Yamaoka S, Urade R, Kito M.
Cardiolipin molecular species in rat heart mitochondria are sensitive to essential fatty acid-deficient dietary lipids.
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Zeisel SH.
Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones.
Mutat Res. 2011 Oct 20. [Epub ahead of print]

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

Growing Old With Zinc

zinc-supplementsIf you read—and were enlightened by—the newsletter about aging and omega-3 fatty acids, you’ll likely be interested in this one about zinc and its relationship to aging and disease. For a long time, zinc has been associated with a strong immune system, but its connection to aging is a relatively new exploration. Whether zinc deficiency promotes aging or results from it matters little to those who endure its aftermath in their “golden” years.

What Is This Stuff?

Zinc is a mineral essential to all life. In humans, it plays a functional role in immunity, in growth and development, in neurological mechanisms, and in reproduction, as well as in several avenues of cellular metabolism. It performs a structural role in some proteins as a stabilizer and in cell membranes as a guard against oxidative insults and functional impairment (O’Dell, 2000). Additionally, zinc is a component of “zinc fingers,” which are structural domains that are wrapped around a zinc ion and regulate gene expression by acting as transcription factors by cleaving to DNA. Zinc has been found to be integral to programmed cell death, called apoptosis (Truong-Tran, 2000).

Do I Have Enough?

Possibly not. The World Health Organization (WHO) suggests that zinc deficiency is widespread and affects the health and well-being of populations worldwide. The International Zinc Nutrition Consultative group (IZiNCG) has determined that zinc intake is inadequate based on the presence and bioavailability of this micro-nutrient in each country’s food supply. Deficiency in children, especially, raises the risk for diarrheal diseases, pneumonia and malaria, the latter a defined danger for populations so exposed (WHO, 2008). Conservative estimates posit that one-fourth of the world’s population is deficient in zinc (Maret, 2006).

Although zinc deficiency is typically diet-related, it can spring from malabsorption, chronic liver and kidney disease, sickle-cell disease, diabetes, malignancy, and as a result of bariatric surgery, heavy metal exposure and possibly the ingestion of FD&C Yellow #5, known as tartrazine (GPN, 2012). The problem of zinc deficiency has been known for decades, but has received scant attention because it was believed that it could never occur in humans (Prasad, 2003). Yet its burden is outstanding and simply resolved with supplementation. The bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because meat is not part of the vegan regimen. The legumes and plants common to vegetarian diets contain phytates that bind zinc and inhibit its absorption (Hunt, 2003) (Sandstrom, 1997) (Wise, 1995). Considering that poor agricultural, storage, shipping and kitchen practices can take a toll on any food’s nutritional profile, it can readily be seen that deficit is not the impossibility it once was thought to be. Eleven milligrams a day for an adult male and nine for a female is enough to meet nutritional requirements. Doses for children and pregnant women may be retrieved from the Office of Dietary Supplements at the National Institute of Health website (IOM, 2001).

What About Aging?

As we age, our DNA replication may become increasingly undependable because of shortened telomeres, possibly setting the stage for chronic, debilitating diseases, including cancer. There is a substantial body of evidence suggesting that a significant percentage of cancer deaths could be avoided by paying attention to proper nutrition.  Only in this century has zinc been tagged as a vital element in host defense against the initiation and progression of this disease, based partly on zinc’s character as supporting more than three hundred mammalian proteins (Ho, 2004). Because cancer is a disease mostly of the middle and older years, it is fitting to maintain a healthy nutritional intake, including supplementation if needed, noting that the elder population is vulnerable to zinc deficiency.

The pertinence of zinc to the entire immune system is well-documented. The presence of chronic inflammation, whether from physical illness, oxidative stress or the mental challenges of daily asperities, may induce sub-optimal zinc levels for most of us. From this was born the recommendation that zinc be supplemented to at-risk populations, notably the aged (Mocchegiani, 2006). It has been proposed that genetic screening for response to zinc intake be considered in order to maintain a healthy immune system, to ensure the activity of anti-oxidant proteins, and to avoid the frailty and degeneration that often accompany old age (Mocchegiani, 2007).

Among the environmental bombardments suffered by the immune system is cadmium exposure, largely from fossil fuels combustion, but also from some fertilizers, metal refining, and tobacco use. Smokers have four times the cadmium levels as non-smokers, and this may be causative of early atherosclerosis and hypertension, both being risk factors for CVD, but also attenuated by high zinc concentrations (Messner, 2009). The long biological half-life of cadmium only compounds the concerns by presenting a cumulative effect, resulting in sterilizing, teratogenic and carcinogenic ramifications (Bin, 1994). The physical attack from cadmium and cohort environmental insults may lead to a state termed immunosenescence, the gradual deterioration of the immune system brought on by natural age advancement. As soon as you agree that, “Hey, this is just the way it is,” you have already decided to lose the race by a considerable margin. A large part of the aging drama can be explained by an imbalance between pro- and anti-inflammatory complexes, most often resulting in low-grade chronic inflammation. This condition is a driving force behind the frailty and the more common conditions associated with aging (Franceschi, 2007).  The Third Zinc Age Meeting in Madrid offered that zinc supplementation presents a strong case in the management of healthy aging (Mocchegiani, 2006), since  zinc deficiency is constantly observed in the chronic inflammation of old age (Vasto, 2007) (Fabris, 1995).

The absolute requirement for zinc is not known to be higher in the elderly, buttheir intake tends to be low. There are social factors that can interfere withsound dietary habits, loneliness being paramount. Insufficient intake of zinc(from food or supplements) may lead to loss of taste sensation, which leads tounwillingness to eat, which continues the vicious cycle. Drugs that promote zincexcretion (including some diuretics), poor absorption and chronic diseases contributeto the deficit. Although it might not turn back the clock, zinc may be able toslow its forward progression.

References

Bin QH, Garfinkel D.
The cadmium toxicity hypothesis of aging: a possible explanation for the zinc deficiency hypothesis of aging.
Med Hypotheses. 1994 Jun;42(6):380-4.

Daaboul D, Rosenkranz E, Uciechowski P, Rink L.
Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells.
Metallomics. 2012 Oct 1;4(10):1088-97. Epub 2012 Sep 14.

Fabris N, Mocchegiani E.
Zinc, human diseases and aging.
Aging (Milano). 1995 Apr;7(2):77-93.

Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S.
Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans.
Mech Ageing Dev. 2007 Jan;128(1):92-105. Epub 2006 Nov 20.

Garfinkel D.
Is aging inevitable? The intracellular zinc deficiency hypothesis of aging.
Med Hypotheses. 1986 Feb;19(2):117-37.

GPN–General Practice Notebook–a UK Medical reference
http://www.gpnotebook.co.uk/simplepage.cfm?ID=886046736
Accessed 15 October, 2012

Emily Ho
Zinc deficiency, DNA damage and cancer risk
The Journal of Nutritional Biochemistry. Vol 15, Iss 10 , PP 572-578, Oct 2004

Andrea Hönscheid, Svenja Dubben, Lothar Rink, Hajo Haas
Zinc differentially regulates mitogen-activated protein kinases in human T cells
The Journal of Nutritional Biochemistry. Vol 23, Iss 1 , Pp 18-26, Jan 2012

Hunt JR.
Bioavailability of iron, zinc, and other trace minerals from vegetarian diets.
Am J Clin Nutr. 2003 Sep;78(3 Suppl):633S-639S.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001.
http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/#en2

Mahoney MG, Brennan D, Starcher B, Faryniarz J, Ramirez J, Parr L, Uitto J.
Extracellular matrix in cutaneous ageing: the effects of 0.1% copper-zinc malonate-containing cream on elastin biosynthesis.
Exp Dermatol. 2009 Mar;18(3):205-11.

Maret W, Sandstead HH.
Zinc requirements and the risks and benefits of zinc supplementation.
J Trace Elem Med Biol. 2006;20(1):3-18. Epub 2006 Feb 21.

Messner B, Knoflach M, Seubert A, Ritsch A, Pfaller K, Henderson B, Shen YH, Zeller I, Willeit J, Laufer G, Wick G, Kiechl S, Bernhard D.
Cadmium is a novel and independent risk factor for early atherosclerosis mechanisms and in vivo relevance.
Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1392-8.

Mocchegiani E, Malavolta M, Marcellini F, Pawelec G.
Zinc, oxidative stress, genetic background and immunosenescence: implications for healthy ageing.
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Mocchegiani E.
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O’Dell BL.
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Prasad AS, Fitzgerald JT, Hess JW, Kaplan J, Pelen F, Dardenne M.
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Prasad AS.
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Sandström B.
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Truong-Tran AQ, Ho LH, Chai F, Zalewski PD.
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Vasto S, Mocchegiani E, Malavolta M, Cuppari I, Listì F, Nuzzo D, Ditta V, Candore G, Caruso C.
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Carmen P. Wong, Kathy R. Magnusson, Emily Ho
Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation
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Childhood and maternal undernutrition
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Laura E. Caulfield and Robert E. Black
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Good News About Coffee

cup-of-coffee-on-saucerThe inveterate coffee drinkers among us will appreciate the good news about one of our favorite beverages. After all the flak we took about the vices of coffee, now’s the chance to respond. After water and tea, coffee is the next most popular drink on the planet, having a starring role in the history of several cultures. It came from the Muslim world, travelled to Italy and then to the rest of Europe, finally landing in the New World. At one time, it was limited only to religious observances.

The coffee bean is contained inside a “cherry” that grows on a small evergreen bush.  The Arabica strain is the more highly regarded of the two chief varieties, but the robusta strain is more resistant to the diseases peculiar to this plant, though less flavorful and more bitter. Arabica prefers the coolness of the mountainside; robusta will grow at lower elevations and in warmer climates. Since the best tasting coffee really is mountain grown, the sales talk of a particular brand is true. But Mrs. Olsen never told us that other brands also use mountain grown beans. She merely capitalized on a little-known fact.

One effect of coffee consumption is moderately elevated blood pressure, which is not surprising because caffeine is a stimulant. Italian studies done in the early 1990’s found that 200 milligrams of caffeine, about two cups’ worth, could raise systolic blood pressure by 10% and diastolic by 5% for up to two hours after consumption. The mechanism points to vasoconstriction (which has its own benefits), but researchers found no variation in heart rate or cardiac contractility (Casiglia, 1991), leading to an assumption that this temporary state is not a major concern, especially in light of later studies that reported no association between long-term coffee consumption and increase of cardiovascular complications (Mesas, 2011) or risk of hypertension (Geleijnse, 2008) (Klag, 2002).

Vitamin B6, known as pyridoxine, is a nutrient occasionally used to tame morning sickness in pregnancy and the throes of PMS. It’s also been used to address homocysteine imbalance, carpal tunnel syndrome, immunity deficiencies, and various behavioral/psychiatric issues. However, careless dosing of vitamin B6 can cause medical concerns that outweigh the benefits of producing the monoamine neurotransmitters, serotonin and dopamine. Large doses of B6 over a period of time can cause nerve fiber damage, particularly auditory neuropathy. You’d never think that coffee can prevent and treat this malady, but it does (Hong, 2008). One active coffee component is called trigonelline (Hong, 2009), an alkaloid also found in pumpkin that is able to modulate blood glucose (van Dijk, 2009) (Yoshinari, 2009). Because auditory neuropathy may be attenuated by trigonelline, why can’t the peripheral neuropathy of diabetes or physical trauma likewise be eased? It’s worth a look (Zhou, 2012).

Late-life dementia and Alzheimer’s disease (AD) are concerns shared by an aging population across the globe. Finnish studies followed a number of middle-agers for more than twenty years, documenting their coffee (and tea) consumption along the way.  Focusing more on caffeine than on coffee’s lesser-known constituents, researchers found that, over the long haul, those who drank three to five cups of coffee a day at midlife had a lower risk of dementia and AD in old age (Eskelinen, 2009, 2010).  American studies later found that long-term coffee consumption protects against cognitive impairment by reducing the formation of amyloid beta, the protein that forms the plaques associated with AD. Here it was inferred that caffeine is part of a synergy that affords the desired effect, with many coffee constituents not yet identified (Cao, 2011).

Because early research had indicated that coffee may be protective against conditions other than neurological, scientists took the trigonelline link a little further. It’s accepted that people with diabetes are at risk for cognitive dysfunction. Initially, it was proposed that coffee was merely to be explored as a tool in the management of diabetes and related sequelae (Biessels, 2010). It was realized, however, that caffeine can decrease the risk of type 2 diabetes and consequent cognitive decline (Salazar-Martinez, 2004) (Tuomilehto, 2004).

In general, coffee increases plasma antioxidant capacity, possibly because of the contribution, bioavailability and activity of its particular group of polyphenols, including chlorogenic acid, one component linked to a reduction of type 2 diabetes risk by virtue of delaying intestinal glucose absorption and the inhibition of gluconeogenesis (Ong, 2010) (Tunnicliffe, 2011). Other medical conditions are purported to be influenced by coffee’s mechanisms, including gastrointestinal diseases (Inoue, 1998), gallstones (Leitzmann, 1999), and Parkinson’s disease (Checkoway, 2002) (Blanchette, 2000).

If coffee has a down side, it’s that it can interact with some drugs, most notably quinolone antibiotics, such as ciprofloxacin and its kin, which increase caffeine concentrations by inhibiting its clearance (Harder, 1989). Coffee’s popularity cannot be ignored. Just look at all the coffee options that run the gamut from hot to cold, from sweet to sweeter, and from low-cal to mega-cal. Since the 1989 expiration of a global agreement to stabilize supply, availability has fluctuated—and so has the price. You can’t even get the cup for a dime any more.

References

Biessels GJ.
Caffeine, diabetes, cognition, and dementia.
J Alzheimers Dis. 2010;20 Suppl 1:S143-50.

Campdelacreu J.
Parkinson disease and Alzheimer disease: environmental risk factors.
[Article in English, Spanish]

Neurologia. 2012 Jun 13. [Epub ahead of print]

Cao C, Wang L, Lin X, Mamcarz M, Zhang C, Bai G, Nong J, Sussman S, Arendash G.
Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice.
J Alzheimers Dis. 2011;25(2):323-35.

Casiglia E, Bongiovì S, Paleari CD, Petucco S, Boni M, Colangeli G, Penzo M, Pessina AC.
Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study.
J Intern Med. 1991 Jun;229(6):501-4.

Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD.
Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.
Am J Epidemiol. 2002 Apr 15;155(8):732-8.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M.
Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study.
J Alzheimers Dis. 2009;16(1):85-91.

Eskelinen MH, Kivipelto M.
Caffeine as a protective factor in dementia and Alzheimer’s disease.
J Alzheimers Dis. 2010;20 Suppl 1:S167-74.

Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, Boeing H
Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.
Am J Clin Nutr. 2012 Apr;95(4):901-8.

Yoichi Fukushima, Takashi Ohie, Yasuhiko Yonekawa, Kohei Yonemoto, Hiroki Aizawa, Yoko Mori, Makoto Watanabe, Masato Takeuchi, Maiko Hasegawa, Chie Taguchi and Kazuo Kondo
Coffee and Green Tea As a Large Source of Antioxidant Polyphenols in the Japanese Population
Journal of Agricultural and Food Chemistry 2009 57 (4), 1253-1259

Gelber RP, Petrovitch H, Masaki KH, Ross GW, White LR.
Coffee intake in midlife and risk of dementia and its neuropathologic correlates.
J Alzheimers Dis. 2011;23(4):607-15.

Geleijnse JM.
Habitual coffee consumption and blood pressure: an epidemiological perspective.
Vasc Health Risk Manag. 2008;4(5):963-70.

Harder S, Fuhr U, Staib AH, Wolff T.
Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations.
Am J Med. 1989 Nov 30;87(5A):89S-91S.

Head KA.
Peripheral neuropathy: pathogenic mechanisms and alternative therapies.
Altern Med Rev. 2006 Dec;11(4):294-329.

Hermansen K, Krogholm KS, Bech BH, Dragsted LO, Hyldstrup L, Jørgensen K, Larsen ML, Tjønneland AM.
Coffee can protect against disease
Ugeskr Laeger. 2012 Sep 24;174(39):2293-2297.

Hong BN, Yi TH, Park R, Kim SY, Kang TH.
Coffee improves auditory neuropathy in diabetic mice.
Neurosci Lett. 2008 Aug 29;441(3):302-6. Epub 2008 Jun 22.

Hong BN, Yi TH, Kim SY, Kang TH.
High-dosage pyridoxine-induced auditory neuropathy and protection with coffee in mice.
Biol Pharm Bull. 2009 Apr;32(4):597-603.

Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, Grobbee DE, Batty D, Woodward M.
Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis.
Arch Intern Med. 2009 Dec 14;169(22):2053-63.

Inoue M, Tajima K, Hirose K, Hamajima N, Takezaki T, Kuroishi T, Tominaga S.
Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan.
Cancer Causes Control. 1998 Mar;9(2):209-16.

Kaiser permanante Division of Research
Coffee Drinking and Caffeine Associated with Reduced Risk of Hospitalization for Heart Rhythm Disturbances
3/2/2010

Klag MJ, Wang NY, Meoni LA, Brancati FL, Cooper LA, Liang KY, Young JH, Ford DE.
Coffee intake and risk of hypertension: the Johns Hopkins precursors study.
Arch Intern Med. 2002 Mar 25;162(6):657-62.

Leitzmann MF, Willett WC, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E.
A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.
JAMA. 1999 Jun 9;281(22):2106-12.

Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E.
The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis.
Am J Clin Nutr. 2011 Oct;94(4):1113-26. Epub 2011 Aug 31.

Oba S, Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Shimizu H.
Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women.
Br J Nutr. 2010 Feb;103(3):453-9. Epub 2009 Oct 12.

Ong KW, Hsu A, Tan BK.
Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes.
PLoS One. 2012;7(3):e32718. Epub 2012 Mar 7.

Richelle M, Tavazzi I, Offord E.
Comparison of the antioxidant activity of commonly consumed polyphenolic beverages (coffee, cocoa, and tea) prepared per cup serving.
J Agric Food Chem. 2001 Jul;49(7):3438-42.

Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR.
Association of coffee and caffeine intake with the risk of Parkinson disease.
JAMA. 2000 May 24-31;283(20):2674-9.

Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FB.
Coffee consumption and risk for type 2 diabetes mellitus.
Ann Intern Med. 2004 Jan 6;140(1):1-8.

Tunnicliffe JM, Eller LK, Reimer RA, Hittel DS, Shearer J.
Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats.
Appl Physiol Nutr Metab. 2011 Oct;36(5):650-9. Epub 2011 Oct 6.

Tuomilehto J, Hu G, Bidel S, Lindström J, Jousilahti P.
Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women.
JAMA. 2004 Mar 10;291(10):1213-9.

van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM.
Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.
Diabetes Care. 2009 Jun;32(6):1023-5. Epub 2009 Mar 26.

Yoshinari O, Sato H, Igarashi K.
Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.
Biosci Biotechnol Biochem. 2009 May;73(5):1033-41. Epub 2009 May 7.

Zhou J, Chan L, Zhou S.
Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.
Curr Med Chem. 2012 Jul 1;19(21):3523-31.

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

OMEGA-3’S Effect On Aging

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

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

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

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

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

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

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

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

References

Adler N, Pantell M, O’Donovan A, Blackburn E, Cawthon R, Koster A, Opresko P, Newman A, Harris TB, Epel E.
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Burghardt PR, Kemmerer ES, Buck BJ, Osetek AJ, Yan C, Koch LG, Britton SL, Evans SJ.
Dietary n-3:n-6 fatty acid ratios differentially influence hormonal signature in a rodent model of metabolic syndrome relative to healthy controls.
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Epel E.
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

What Everyone Should Know About Black Tea

black-teaFor a long time we’ve heard that green tea does this and green tea does that and green tea has this and that benefit, while poor old black tea sits in the cupboard waiting for its chance on the stage. There’s little question that green tea and its army of polyphenols have distinct nutritional value. It promises to reduce the risk of cardiovascular disease, kidney stones, tooth decay and cancer, while it improves bone density and cognitive function. Now we know that black tea has its own virtues.

Tea doesn’t start out being black. It’s just more oxidized than the others, and that gives it a stronger taste. Green tea will lose its flavor in a year, but black will endure. Like most leafy plants, tea leaves start to wilt and oxidize soon after being picked, and then darken as the chlorophyll breaks down and tannins are released. The enzymes that cause the darkening are interrupted by heating the leaves at the appropriate time, controlling moisture to prevent mold from growing. The tannins that give tea its astringency are not peculiar to that plant, but appear in a wide variety of flora. They’re perhaps best known for use in tanning leather. But a lesser known property is tannin’s ability to inhibit the action of some viruses (Lu, 2004), bacteria such as Staphylococcus aureus (Akiyama, 2001), and flagellate protozoans (Kolodziej, 2005).

An interesting and welcome finding is that black tea may have the potential to stimulate insulin response and reduce blood sugar levels. Keeping those levels steady throughout the day can regulate appetite and reduce the tendency to snack, a definite asset in the battle of the bulge. Although green tea contains a higher percentage of polyphenols, the 5% – 10% found in black tea is sufficient to evoke the insulin response. Subjects who drank either 1.0 or 3.0 grams of black tea, contrasted to those who drank either glucose-laden or caffeine-laden water, experienced significantly lower glucose concentrations after two hours. Insulin levels had increased after ninety minutes (Bryans, 2007). Analysis of the tea discovered substantial polyphenol values.  Almost twenty years earlier, reports showed that polyphenols from any source, in this case legumes, present a negative correlation with glycemic response (Thompson, 1984). The result held true for both diabetes and non-diabetes individuals.

With the exception of water, tea is the most popular beverage worldwide. Despite this, not much is known about the biological availability of black tea polyphenols or the molecular targets that mediate the glycemic effects. Aging and its related attributes appear to be linked to dietary cues, the complexity of gluconeogenesis among them. This metabolic pathway results in the generation of glucose from non-carbohydrate sources, such as from amino acids, including glycine, serine, arginine and glutamine, among others. In fact, only leucine and lysine are not glucogenic. Gluconeogenesis is a target for therapy in type 2 diabetes, which is address by metformin (Glucophage), a hypoglycemic agent that potentiates the action of insulin and inhibits glucose formation (Hunadl, 2000). The active polyphenols in black tea are identified as theaflavins and thearubigins.

Theaflavins are formed as green tea ferments into black or oolong tea. Already known to support lipid metabolism (Maron, 2003) (Lin, 2006), these compounds work with other polyphenols to present additional benefits, including attenuation of inflammation and oxidation (Aneja, 2004) (Leung, 2001). Thearubigins are likewise created, but also offer a reddish tone to a cup of brewed tea. If tea is poorly stored, thearubigins continue to form and adversely affect flavor while simultaneously reducing catechins, which control the qualities of green tea cited in the first paragraph. It is these components that boost the healthful properties of black tea. As they ply their talents, they prevent the glycation that lends itself to the formation of deleterious products that follow the heating of proteins in the presence of sugars, known in the culinary world as the Maillard reaction, or caramelization (Tan, 2008). Glycation risks the manufacture of a compound called methylglyoxal, an element that inhibits insulin signaling and contributes to the pathophysiology of diabetes (Riboilet-Chavey, 2006) (Tan, Apr 2008). By interfering with the production of one element in the process, we just might be able to forestall the ultimate villain—diabetes.

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Amy R. Cameron, Siobhan Anton, Laura Melville, Nicola P. Houston, Saurabh Dayal Gordon J. McDougall, Derek Stewart, Graham RenA
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Methylation And Age: How Old Are You, Really?

innocence-and-experienceHave you noticed that medicine is called a practice? Maybe that’s because everybody isn’t the same. What works for you possibly won’t work for your neighbor, despite that the same doctor prescribes the same medicines for the same reason in the same doses for both of you. The age of individualized medicine is upon us, a time when what goes into your body, whether food or medication or supplement, will be geared toward your individuality. One size will not fit all. This makes sense—finally, as it becomes increasingly evident that our bodies don’t do things at the same rate…like age. Some of us age gracefully; others just get old. Aging can be managed. Getting old can strike out of nowhere, but some scientists think it’s controllable. Attitude matters.

Biologically, our clocks tick at a different rhythm. Once in a while a 70-year-old looks 50; often it’s the reverse. Science has tried to identify markers that quantify the actual rate of aging. First, it looked at telomeres, those aglet-like caps at the ends of chromosomes that shorten with age. (Aglets are the plastic sheaths at the ends of shoelaces that keep them from raveling.)  Telomeres might be part of the picture, but are not the sole influence on aging. DNA methylation is now a target of exploration, where researchers are examining the methylome, the whole set of methylation markers across the genome that almost predictably changes over time. This inquiry is expected to determine a person’s biological age from a single drop of blood. A methylation site gets fuzzier as people age, and the differences between the young and the old become more clearly defined.

Much of what extended life writers and websites would have us believe is bogus. If not backed by hard science, discount most of what you read.  On the other hand, the measurement of human age from recognized molecular profiles has merit, especially in preventing and treating disease and possibly even in the extension of human life. The process of methylation can be inhibited or hastened, depending on what we do and what we swallow.

What is methylation?

Methylation is a biological process in which a methyl group (CH3) is added to one of the amino acids in DNA. The result can suppress harmful activity and help to ensure proper DNA replication by replacing a single hydrogen atom with the whole group. Abnormalities in this process are linked to genetic defects. If it happens to a gene that controls cell division, for example, cell division may be uncontrolled and result in cancer. Methylation is typically brought about by vitamin B12-dependent enzymes, such as methionine synthase, which uses methylcobalamin as a co-factor to turn homocysteine back into methionine and to prevent some forms of anemia. Recently, researchers at the U of CA, San Diego School of Medicine measured more than 485,000 genome-wide markers of methylation in the blood of 656 people, aged from 19 to 101, noting that the process weakens with age, and that different organs within the same body methylate at different rates and efficacies (Hannum, 2012).  The hypomethylation of old age is far separated from the normal methylation of neonates and teenagers. This phenomenon can be seen in a parallel comparison of like sectors of the genome Heyna, 2012). The implications are that lifestyle modifications can prolong the methylation ability of the genome, thus promoting longevity and health.

DNA?

This is the stuff that determines the makeup of all living cells. It consists of two long strands of compounds that are the building blocks of the nucleic acids that eventually control cellular function and heredity. The two strands coil around each other in what is called a double helix, which is a spiral that resembles that of a school notebook. Imagine a pencil inserted into the notebook’s spiral backbone. That pencil represents a material called histone, which forms a spool around which the DNA can wrap itself. It sort of helps to keep the spirals from getting kinked, like what happened to the old slinky you had to throw away. Histones are important because they keep the DNA under control by compacting it. Otherwise, the strand would be about six feet long. It’s tantamount to the modern telephone cords that coil to save space on the floor. Old-fashioned cords were straight, uncoiled wires that always got in the way of whatever you wanted to do. Methylation keeps histones in good shape. It is felt that histones influence the signaling pathways that may extend longevity (Han, 2012). If so, the inference is simple—keep histones well, live longer, or at least live healthier.

How Do I Do This?

The answer is too simple to ignore, but often is. For some obscure reason, humans look for the complicated way of doing things. Diet is an important element of genome methylation; maybe even paramount in the support of the process. Practically nothing is easier to implement, but keep in mind that all food is not created equal. Grass-fed meat, for example, is lower in total fat than grain-fed. A sirloin from a grass-fed steer has about half the fat of a grain-fed steer. It also contains conjugated linoleic acid, an omega-3 fat found in the chloroplasts of grass that may play a role in weight management (Whigham, 2007) and protect against some cancers (Ip, Aug, 1994) (Ip, Mar, 1994). Pastured hens lay eggs with goodly amounts of n-3 fats in contrast to factory-raised. Simply, the vitamin B12 from animal products supplies a methyl molecule.

Eating raw nuts and seeds gets you about 6 grams of protein an ounce, plus the polyunsaturated fats you need to fight inflammation and to prevent cardiovascular issues. Adding green leafy vegetables and legumes supplies additional folate, which is a noteworthy methyl donor. Supplementation with B12 and folinic acid or methyltetrahydrofolate is not out of place, and is a prudent move if one’s diet is less than wholesome. The promise of long-term health, well-being and extended life might be more real than we imagined. And it requires little effort.

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*These statements have not been evaluated by the FDA.
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Mood Boosts Elder Brain Power

pleased-manWhen you’re in a good mood, it’s almost amazing what you can accomplish. This has little to do with emotions and even less with temperament. The former are short-lived and specific, and may be turned on by a single stimulus. The latter are characteristics that are seemingly innate rather than learned. Moods may be disarrayed, as in depression and bipolar disorder, and are subjective, although they may be inferred by conduct or body language. Many things can trigger a bad mood, and what disturbs one person might be ridiculous to another. In some circles, bad mood is believed to originate when one’s ego becomes threatened by a situation, event or condition beyond his control. Foul moods can interfere with many of our individual enterprises and ventures, not the least of which are the mental acrobatics that have seen us through thick and thin from youth to the extremes of middle-age. With age there may come decline, physically, emotionally and mentally. But we may have more control over this than previously thought. Is it possible that we can improve physical health, which will improve mood, which will improve mental faculties?

We already know that diet and exercise can enrich physical well-being and probably extend life…and the quality of life as we live it. Newspapers, magazines, the internet, television programs, and even the beauty parlor help to deliver information about longevity and agelessness. With a little thought, it’s possible to separate the wheat of the message from the chaff. The time at which old age begins is subjective, and ranges from sixty-five to the mid seventies, depending on whom you ask. Most of us believe that old age is for other people. That attitude will bless you with almost-eternal youth.

A vagary of aging is the diminution of working memory and instant decisiveness. The invincibility of youth gives way to the deliberations of middle-age and eventually to the tentativeness of senior citizenship. The culmination of this time line puts us on the game board square labeled “moody” or “testy” or “cranky.”  Modern research tells us that good mood can counterbalance these vagaries, and that trivial gestures, like giving a person a small bag of candy, can help to improve performance on tests of decision making and working memory.

In an interesting work done at Decision Research, in Oregon, good mood in twenty-three seniors was engendered with a bag of candy and a Thank-you card as a reward for agreeing to take part in the study. An equal number of seniors received no reward, and were considered the control group. Both groups were assigned to individual computers. The candy group saw happy faces and smiling suns on their sky-blue backgrounds. The control group saw neutral round images with no facial features. In tests of speed and accuracy that entailed experiential, sequenced learning, the candy group made significantly better choices than the neutral group. An extension of this mode to real life is analogous to meeting a person for the first time, and having to decide if she or he is trustworthy. What the study suggests is that people in a good mood are able to make such a determination faster and more accurately.

Working memory is linked to learning outcomes, encompassing the recall of instructions and the ability to complete an activity based on them. It boils down to how much information you can hold onto at one time. This function is important to decision making. The seniors in the happy group fared better than the others (Carpenter, 2013). It can be such that those who are suddenly elated forget their aches and pains and their trials and tribulations, thus vouching for the promises of a good mood. If good mood improves memory, then being able to remember might just improve mood, particularly for those beleaguered with cognitive interruptions.

Lots of factors can throw the body out of balance, but if you are chemically balanced, your moods will also be. It has been established that positive feelings facilitate working memory and decision making. Nutrients can do the same, especially if they are proportioned to maintain stable blood sugar. Because some seniors are prone to the loss of gustatory sensation, eating may be a chore rather than a pleasure, in which case nutrient supply may be shallow. Supplementation with at least one nutrient–vitamin B6, for example—has been found to improve storage of information (Deijen, 1992).

When the elderly are able to cheer each other on, as in a community setting, they are more apt to comply with those dietary interventions aimed at physical and mental maintenance. That flavor enhancement induces appetite by overcoming perceptual losses has been demonstrated at home and institutional settings (Schiffman, 1993), and the inclusion of essential fatty acids, whether from foods or supplements, has been found to enhance cognitive function (Yehuda, 2012) and, thereby mood (Parker, 2006) (Stahl, 2008).

Keeping Grandpa or Grandma in a good mood is essential to family serenity. In a time when several generations might live together, this could be as simple as letting them control the remote. Trading Ed Sullivan reruns for peace of mind is probably worth it if Gramps can simultaneously offer a compelling review of last Sunday’s pot roast dinner.

References

Burt, Diana Byrd; Zembar, Mary Jo; Niederehe, George
Depression and memory impairment: A meta-analysis of the association, its pattern, and specificity.
Psychological Bulletin, Vol 117(2), Mar 1995, 285-305.

Carpenter SM, Peters E, Västfjäll D, Isen AM.
Positive feelings facilitate working memory and complex decision making among older adults.
Cogn Emot. 2013;27(1):184-92. doi: 10.1080/02699931.2012.698251. Epub 2012 Jul 6.

Carlson LE, Sherwin BB.
Steroid hormones, memory and mood in a healthy elderly population.
Psychoneuroendocrinology. 1998 Aug;23(6):583-603.

J. B. Deijen, E. J. van der Beek, J. F. Orlebeke, H. van den Berg
Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort
Psychopharmacology. December 1992, Volume 109, Issue 4, pp 489-496

Eric Eich
Searching for Mood Dependent Memory
Psychological Science March 1995 vol. 6 no. 2 67-75

Parker G, Gibson NA, Brotchie H, Heruc G, Rees AM, Hadzi-Pavlovic D.
Omega-3 fatty acids and mood disorders.
Am J Psychiatry. 2006 Jun;163(6):969-78.

Schiffman SS, Warwick ZS.
Effect of flavor enhancement of foods for the elderly on nutritional status: food intake, biochemical indices, and anthropometric measures.
Physiol Behav. 1993 Feb;53(2):395-402.

Stahl LA, Begg DP, Weisinger RS, Sinclair AJ.
The role of omega-3 fatty acids in mood disorders.
Curr Opin Investig Drugs. 2008 Jan;9(1):57-64.

Teasdale, John D.; Fogarty, Sarah J.
Differential effects of induced mood on retrieval of pleasant and unpleasant events from episodic memory.
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Wells AS, Read NW, Laugharne JD, Ahluwalia NS.
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Yehuda S.
Polyunsaturated fatty acids as putative cognitive enhancers.
Med Hypotheses. 2012 Oct;79(4):456-61. doi: 10.1016/j.mehy.2012.06.021. Epub2012 Jul 15.

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

When Does Old Age Begin?

pensiveThe boundary between seniors and old people has shifted over the years. Some people are deemed old because they are grandparents—even at forty-five. Others become old when they retire, regardless of age or circumstance. Despite getting a seniors’ discount at age 50, or 60 or 65, some folks don’t fit the definition because of their mindset, Social Security or not. Now that Social Security eligibility in the United States is headed toward 70 and a whole lot of folks are still working, old age might never be attainable. The physical and mental changes can sneak up on us, though. Wrinkles and liver spots, gray hair (if you have hair), reduced lung capacity and voice changes wrought by loss of elasticity are signs of aging. But the mental changes, namely forgetfulness and full-blown dementia, are the more frightening. Depressed mood is common.

Because “out of sight is out of mind” may be truer than we like to think, grandma and grandpa may be among the forgotten, especially if they live more than a few hours distant from the rest of the family. If still a couple, the septuagenarian or octogenarian pair might fare quite well. But if left alone, by death or incapacitation, faring well might be history. Those over age 75 may not be as helpless as they were a decade ago, but their nutrition status is probably the same—miserable. Were it not for assisted living facilities or equivalent communal arrangements, or for home care organizations, or even for dedicated family, many seniors would be categorically undernourished or malnourished. One reason is being alone at the table. The isolated person waits for hunger to drive him to eat, often being satisfied with a bowl of high-carb-low-protein cereal, a can of super-salty soup, or a questionably prepared frozen something. Being alone, regardless of age, has been likened to smoking fifteen cigarettes a day (Cresswell, 2010).

Geriatrics is not the same as gerontology, the latter being the study of the aging process itself, which looks at the psychological and biological aspects. Geriatrics is a sub-specialty of adult medicine that focuses on the aged, which is a time of life determined more by need than by years. An aged body will show a decline in organ systems, some of which can be blamed for choices made earlier in life, including smoking, sedentary lifestyle and poor dietary habits. It’s possible that these can be overcome by quitting, moving and choosing foods wisely.

Nutrient deficiency is common in the elderly because of several factors:  reduced food intake, lack of variety, medications that cause nutrient depletions, financial insecurity, poor oral condition, loss of gustatory sensation, and other dreadful conditions, among which are an uncaring family and a desolate social life. There are some things a single senior can do to help ensure more wholesome intake. Eating away from the kitchen, as on a porch or patio, might excite appetite. Setting the table with a placemat and flowers to brighten things up can make a difference. Inviting neighbors or sharing cooking time helps to encourage mindful eating. The bottom line is that nutrition is a major determinant in aging well because it promotes health and functionality.

Meals have often added a sense of security and meaning to life. That’s hard to get when alone. A single who is sedentary also has a reduced energy need. If a comparable reduction in energy intake is not made, body fat will increase, partly because of choosing foods that are energy-dense instead of nutrient-dense.  This concern requires closer attention than at any other time of life.

Dehydration is a form of malnutrition that is a major problem among those over eighty. Blunted thirst sensation is partly the cause, but so too are medications, cognitive decline and fear of incontinence. Besides constipation, cognitive decline can worsen and death can result from inadequate hydration.

Without enough protein, frailty, lowered immune function and impaired wound healing are issues to face. The RDA of 0.8 grams of protein per kilogram of body weight still holds true in old age. In fact, a little more protein can help to prevent sarcopenia, the wasting of muscle mass attributed to aging. Up to twice as much is still healthy.

The depression that is known to accompany bereavement causes malnutrition and leads to unfavorable outcomes. Loss of appetite in such a situation is common, but the encouragement to eat by a caring family or empathic social network can stave off negative consequences.  Measurement of depressive symptoms using accepted diagnostic tools indicate that as many as forty percent of seniors fit the category, with a considerable number being malnourished, the two states being reciprocal (Ahmadi, 2013) (Mokhber, 2011).

Maintaining nutrition homeostasis is a challenge in the elderly to begin with. Those who are homebound by choice or by chance don’t realize their dietary needs. Some don’t care. But it’s necessary to provide enough protein to maintain tissue integrity, muscle mass and immune function.  We mistakenly think that old age translates to limited kidney function and that protein will unnecessarily tax kidneys. That’s not always the case, especially if hydration is adequate. Someone needs to be there to lead the parade. Loneliness is a complex response to lack of company or to feelings of being disconnected. It can occur even in a household filled with people. As odd as it may sound, loneliness interferes with good health by increasing susceptibility to viral attacks and by intensifying inflammatory responses to stressors (Jaremka, Aug 2013, Jul 2013). The prospect of eating alone reduces appetite, but the opposite is true. Being with family and friends is the best appetite stimulant for the elderly.

References

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Adam Cresswell, Health editor
Isolation as harmful as smoking 15 a day
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http://www.theaustralian.com.au/news/health-science/isolation-as-harmful-as-smoking-15-a-day/story-e6frg8y6-1225898190216#sthash.5x6gP5ky.dpuf

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