In aging and many disease states, the energy production capacity of the body’s cells is diminished. The mitochondria are the structures within the cell responsible for generating energy from oxygen and nutrients. If their number is reduced or their function is impaired, free radicals are produced and damaging toxins accumulate in the cells. These toxins further damage the mitochondria and impair other aspects of cellular function. Many of the most common health problems, such as obesity, diabetes, and many problems associated with aging, arise from problems in cellular energy production. As one group of researchers has put this, "[a]ging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan."¹ Another has observed, "[m]itochondrial biogenesis [the creation of new mitochondria] is a key physiological process that is required for normal growth and development and for maintenance of ongoing cellular energy requirements during aging."² These observations link two key aspects of mitochondrial health, preventing and removing damaged mitochondria (mitophagy) and creating new mitochondria (mitogenesis).

Although the importance of the mitochondria as a central point of health has been accepted for decades, over the last few years the understanding of the mechanisms involved has changed significantly. Twenty or ten years ago, antioxidants and the free radical theory of aging largely dominated thinking. Today, the importance of mitochondrial biology linking basic aspects of aging and the pathogenesis of age-related diseases remains strong, yet the emphasis has changed. The focus has moved to mitochondrial biogenesis and turnover, energy sensing, apoptosis, senescence, and calcium dynamics.³

What Promotes Mitochondrial Biogenesis?
The body maintains a complex network of sensors and signaling functions to maintain stability despite a constantly changing environment and numerous challenges. Of special note is the concept of hormesis, meaning a state in which mild stress leads to compensation that improves the ability of the body to respond in the future to similar challenges. It turns out that many of the approaches that are associated with longevity and healthy aging promote hormesis. In terms of mitochondria biogenesis, these include caloric restriction, certain nutrient restrictions or shortages, caloric restriction mimetics, and exercise.

Many of the mechanisms that activate mitochondrial biogenesis in the face of hormesis have been elucidated. Keeping in mind that there always must be a balance between the elimination of worn-out and defective mitochondria and the generation of new ones, the activators of both actions can overlap. For instance, low energy levels (caloric restriction) and increased reactive oxygen species/free radicals can promote the activity of special cellular control points. These include activating metabolic sensors such as AMP kinase/ AMPK (adenosine monophosphate kinase) and the protein known as SIRT1 (sirtuin 1, i.e., silent mating type information regulation 2 homolog 1). Activated AMPK is an indicator that cellular energy is low and serves as a trigger to increase energy production. It inhibits insulin/IGF-1/mTOR signaling, all of which are anabolic and can lead not just to tissue production, such as muscle growth, but also to fat storage. Along with SIRT1, AMPK activates the biogenesis of new mitochondria to enable the cell to generate more energy. At the same time, activated AMPK and SIRT1 increase the activity of a tumor suppressor that induces mitophagy. The balance of the dual activations replaces defective mitochondria with newly formed functionally competent mitochondria.

A key to health and healthy aging is to regulate the catabolic processes via controlled amounts and types of stressors such that worn out mitochondria are removed without overshooting the mark and reducing overall cellular and tissue functionality. The most successful way to maintain this balance is to follow the body’s own natural metabolic signals rather than to attempt to override the body’s checkpoints. AMPK and SIRT1 ultimately are energy/nutrient sensors or control points. Hence rather than attempting to manipulate these directly, it likely is safer and ultimately more effective to address the factors in the cell that these sensors sense. The recent attention in the issue of aging to the role of NAD+ (the oxidized form of nicotinamide adenine dinucleotide) is a good example of this principle. Directions coming from the nucleus of the cell that help to regulate the normal production of NAD+ and the ratio between distinct pools found in the cytoplasm and in the mitochondria decline with age. The changes in the NAD+ from the nucleus lead to a disruption on the mitochondrial side. In terms of energy production, it is a bit like losing a link or two in the timing chain on your car engine with a resultant reduction in engine efficiency. To date, attempts to increase NAD+ in cells via supplementation with precursors have not proven particularly successful. Major benefits have been demonstrated in animal models only in the already seriously metabolically impaired or the relatively old. Recent research on oral supplementation has led to at least one extremely difficult article which, at least in this author’s opinion, delivers more smoke than heat.4,5 There is, however, an argument to the effect that supplementing together both nicotinamide riboside (a NAD+ precursor) and a sirtuin activator, such as pterostilbene, may prove to be more successful.

It turns out that there are key points in normal cellular energy generation processes that strongly influence the NAD+ pools available for the cell to draw upon and the rate at which NAD+ can be replaced in these pools. Aging has been shown to promote the decline of nuclear and mitochondrial NAD+ levels and to increase the risk of cancer along with components of the metabolic syndrome. It is significant that the risks of these conditions can be reduced in tandem. Three places to start are 1) the pyruvate dehydrogenase complex, 2) the tricarboxylic acid cycle (TCA cycle) also known as the Krebs Cycle, and 3) the malate shuttle. A fourth junction is Complex I of the electron transport system, again, in the mitochondria.6 Manipulation of steps (1) and (2) already is being used in cancer treatment.7 Readily available dietary supplements can influence all four of these metabolic bottlenecks.

Supplements for Promoting Mitochondrial Biogenesis
Medicine has started to pay a great deal of attention to effecting mitochondrial biogenesis through not just drugs, but also dietary supplements. Those interested should go online and look up "Mitochondrial Biogenesis: Pharmacological Approaches" in Current Pharmaceutical Design, 2014, Vol. 20, No. 35. Quite a few options are mentioned, including well known compounds, such as R-lipoic acid (including with L-carnitine), quercetin and resveratrol, along with still obscure supplements, including various triterpenoids and the Indian herb Bacopa monnieri.

Pomegranate, French White Oak and Walnuts
The pomegranate, with its distinctive scarlet rind (pericarp) and vibrantly colored seed cases (arils), is one of the oldest cultivated fruits in the world. This exotic fruit features prominently in religious texts and mythological tales and has been revered through the ages for its medicinal properties. An image of a pomegranate even can be found on the shield of the British Royal College of Medicine. Numerous studies have demonstrated the benefits of the fruit for cardiovascular health with other benefits suggested in areas ranging from arthritis to stability of cell replication to bone health. Now a study in Nature Medicine (July 2016) has uncovered perhaps the most important benefit of all, the ability of pomegranate compounds (ellagitannins) transformed by gut bacteria to protect the mitochondria of the muscles and perhaps other tissues against the ravages of aging. The mitochondria are the energy generators of the cells and the weakening of this energy generating function in an increasing percentage of mitochondria as we age is a primary source of physical decline over the years. Urolithin A, a byproduct of gut bacterial action on pomegranate compounds, allows the body to recycle defective mitochondria and thereby slow or even reverse for a time some of the major aspects of aging. The lifespan in a nematode model of aging was increased by more than 45 percent. Older mice in a rodent model of aging exhibited 42 percent better exercise endurance. Younger mice also realized several significant benefits.⁸

Beginning almost three decades ago, there were numerous speculations in the research world regarding the so-called "French Paradox" in which the French consumed quite large amounts of saturated fat in the form of butter and cheese, yet consistently experienced much lower rates of cardiovascular disease than did Americans. Not only that, the French, especially in the southwest of the country, typically led longer lives even in the areas noted for consuming large amounts of goose fat and pate de foie gras, which is to say, not just the Mediterranean diet based on olive oil, etc. One hypothesis put forth very early on was that it was the French consumption of red wine that protected them. It was thought that red wine components, including anthocyanidins, proanthocyanidins and resveratrol, are the protective compounds. Not considered until recently is that French red wines traditionally have been aged in casks made from white oak (Quercus robur). White oak contains roburin A, a dimeric ellagitannin related chemically to punicalagin. Human data show relatively good absorption and conversion of roburins into substances including urolithin A and ellagic acid—as compared with ellagitannins in general, which evidence only poor absorption. Hence, the benefits of good red wine traditionally produced and good cognac (also aged in oak barrels) involve urolithin A. Notably, the benefits of roburins, most likely derived from the conversion to urolithin A, go beyond mitophagy to include ribosomes, referring to cell components that translate DNA instructions into specific cellular proteins.^9,10,11,12

Other sources of ellagitannins have been shown to lead to the production of urolithin A by bacteria in the human gut. Not surprisingly, sources of ellagitannins are foods long associated with good health longevity, including not just pomegranate and oak-aged red wine, but also walnuts (and a smattering of other nuts), strawberries, raspberries, blackberries, cloudberries and even black tea in small amounts.

Exercise and Pyrroloquinoline Quinone (PQQ)
Peroxisome proliferator-activated receptor gamma coactivator (PGC-1á) is the master regulator of mitochondrial biogenesis.¹³ Exercise is perhaps the most significant activator of PGC-1á that most individuals can access. Exercise, furthermore promotes mitochondrial biogenesis through a number of other pathways, especially endurance and interval training.¹⁴

There are non-exercise options. You can’t take PGC-1á orally because it is a large protein molecule which does not survive digestion. PQQ is a small molecule that is available when ingested and that increases circulating PGC-1á. PQQ supplementation leads to more mitochondria and more functional mitochondria.¹⁵

Fasting, Ketogenic Diets and Fasting-Mimicking Supplements As already discussed, fasting promotes mitochondrial biogenesis by AMPK activation.¹⁶ AMPK senses the energy status of the cell and responds both to acute shortages, such as that induced by exercise, and to chronic shortages, such as from fasting. Probably due to an overall reduction in metabolic rate, chronic caloric restriction (as opposed to intermittent fasting) contributes to the health of mitochondria rather than biogenesis.¹⁷ The robustness of AMPK response decreases with age.¹⁸

Ketogenic diets (very low carbohydrate diets) also promote increases in mitochondria.¹⁹ Few individuals are willing or able to follow ketogenic diets chronically just as few individuals are willing to undergo routine fasts. Fasting-mimicking supplements offer an alternative approach. The dietary supplement (-)–hydroxycitric acid (HCA) is the best researched of these compounds. (Keep in mind that there is a vast difference in the efficacy of commercially available forms.²⁰) Researchers have proposed that HCA used properly can activate mitochondrial uncoupling proteins and related effects.²¹

Furthermore, according to a study published in the journal Free Radical Research in 2014, HCA improves antioxidant status and mitochondrial function plus reduces inflammation in fat cells.²² Inflammation is linked to the metabolic syndrome at the cellular level by way of damage to the antioxidant enzyme system (e.g., superoxide dismutase, glutathione peroxidase, glutathione reductase) and mitochondria. This damage, in turn, propagates further production of pro-inflammatory mediators (e.g., TNF-á, MCP-1, IFN-ã, IL-10, IL-6, IL-1â). HCA protected fat cells from ER stress by improving the antioxidant status to reduce oxidative stress (i.e., reduce ROS) and improve the function of the mitochondria to short circuit an ER stress—inflammation loop in these cells. Reducing TNF-á is important in that doing so removes a major impediment to mitochondrial biogenesis.²³

Other Supplements to Promote Mitochondrial Biogenesis

Scholarly reviews looking at natural compounds such as those that are found in anti-aging diets suggest yet other supplements to promote mitobiogenesis. For instance, it turns out that hydroxytyrosol, the most potent and abundant antioxidant polyphenol in olives and virgin olive oil, is a potent activator of AMPK and an effective nutrient for stimulating mitochondrial biogenesis and function via what is known as the PGC-1á pathway.²⁴ Another herb with anti-aging effect, this time by activating the malate shuttle mechanism mentioned above, is rock lotus (Shi Lian Hua). This herb has been described in detail in this magazine in the article, "Uncovering the Longevity Secrets of the ROCK LOTUS."²⁵

Conclusion
It is possible to improve the functional capacity of the mitochondria through dietary practices, exercise and supplements. Indeed, a number of compounds have been identified by researchers as mitochondrial nutrients. These compounds work together to increase the efficiency of energy production, to reduce the generation of free radicals, and so forth and so on. Likewise, these nutrients have been shown to improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the ageassociated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. Perhaps best of all, the body can be encouraged both to remove damaged mitochondria (mitophagy) and to create new ones, which is to say, mitochondrial biogenesis.

References:

1. López-Lluch G, Irusta PM, Navas P, de Cabo R. Mitochondrial biogenesis and healthy aging. Exp Gerontol. 2008 Sep;43(9):813–9.
2. Stefano GB, Kim C, Mantione K, Casares F, Kream RM. Targeting mitochondrial biogenesis for promoting health. Med Sci Monit. 2012 Mar;18(3):SC1-
3. Gonzalez-Freire M, de Cabo R, Bernier M, Sollott SJ, Fabbri E, Navas P, Ferrucci L. Reconsidering the Role of Mitochondria in Aging. J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1334-42.
4. Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948.
5. Mitteldorf J. Nicotinamide Riboside —Where’s the Beef? http://joshmitteldorf.scienceblog.com/2014/11/17/nicotinamide-riboside-wheres-thebeef/.
6. Yang Y, Sauve AA. NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta. 2016 Dec;1864(12):1787– 1800.
7. Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: intermediate results of a prospective case series. Anticancer Res.2014 Feb;34(2):973–80.
8. Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med.2016 Aug;22(8):879-88.
9. Pellegrini L, Belcaro G, Dugall M, Corsi M, Luzzi R, Hosoi M. Supplementary management of functional, temporary alcoholic hepatic damage with Robuvit® (French oak wood extract). Minerva Gastroenterol Dietol. 2016 Sep;62(3):245–52.
10. Vinciguerra MG, Belcaro G, Cacchio M. Robuvit® and endurance in triathlon: improvements in training performance, recovery and oxidative stress. Minerva Cardioangiol. 2015 Oct;63(5):403–9.
11. Országhová Z, Waczulíková I, Burki C, Rohdewald P, Ïuraèková Z. An Effect of Oak-Wood Extract (Robuvit®) on Energy State of Healthy Adults-A Pilot Study. Phytother Res. 2015 Aug;29(8):1219–24.
12. Natella F, Leoni G, Maldini M, Natarelli L, Comitato R, Schonlau F, Virgili F, Canali R. Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study. J Agric Food Chem. 2014 Jan 15;62(2):443–53.
13. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res. 2008 Jul 15;79(2):208–17.
14. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem. 2007 Jan 5;282(1):194–9.
15. Bauerly K, Harris C, Chowanadisai W, Graham J, Havel PJ, Tchaparian E, Satre M, Karliner JS, Rucker RB. Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS One.2011;6(7):e21779.
16. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15983–7.
17. Lee CM, Aspnes LE, Chung SS, Weindruch R, Aiken JM. Influences of caloric restriction on age-associated skeletal muscle fiber characteristics and mitochondrial changes in rats and mice. Ann N Y Acad Sci. 1998 Nov 20;854:182–91.
18. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2010;47:69–84.
19. Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007 Jan;48(1):43–58.
20. Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG. Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats. Nutr Metab(Lond). 2005 Sep 13;2:23.
21. McCarty MF. High mitochondrial redox potential may promote induction and activation of UCP2 in hepatocytes during hepatothermic therapy. Med Hypotheses.2005;64(6):1216–9.
22. Nisha VM, Priyanka A, Anusree SS, Raghu KG. (-)–Hydroxycitric acid attenuates endoplasmic reticulum stress-mediated alterations in 3T3-L1 adipocytes by protecting mitochondria and downregulating inflammatory markers. Free Radic Res.2014 Nov;48(11):1386-96.
23. Valerio A, Cardile A, Cozzi V, Bracale R, Tedesco L, Pisconti A, Palomba L, Cantoni O, Clementi E, Moncada S, Carruba MO, Nisoli E. TNFalpha downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents. J Clin Invest. 2006 Oct;116(10):2791–8.
24. Liu J, Shen W, Zhao B, Wang Y, Wertz K, Weber P, Zhang P. Targeting mitochondrial biogenesis for preventing and treating insulin resistance in diabetes and obesity: Hope from natural mitochondrial nutrients. Adv Drug Deliv Rev. 2009 Nov 30;61(14):1343–52.
25. http://www.totalhealthmagazine.com/Anti-Aging/Uncovering-the-Longevity-Secrets-of-the-ROCK-LOTUS.html.

Everything that lives requires enzymes; humans, plants and animals.

Enzymes are protein-based substance found in every living cell. Enzymes can be likened to the starter in your automobile; they ignite the process into action and the speed is dependent on the amount of power under the hood (a full-spectrum of enzymes for specific jobs, working in powerful synchronicity to enhance performance).

In today’s diet of over processed and overcooked food, we can expect to be enzyme deficient. High temperature food preparations can lead to lessened activity or the destruction of many innate food related enzymes. As well, a poor intestinal tract environment which affects most Americans can lead to reduced production of our own enzymes. Therefore, digestive disorders may get their start because of the body’s inability to produce enzymes sufficiently for optimal digestion, absorption, and elimination leading to chronic disorders or discomfort.

Trivialized, untreated, over self-medicated and misunderstood, weak gastrointestinal conditions chronically plague more than 95 million Americans. Avoiding or overcoming digestive enzyme deficiencies is imperative to overall health and longevity.

We suggest establishing a health reserve is dependent upon supplementation with full spectrum enzymes that act as the engines to carry the load for our digestive well-being.

Trends

by Karen DeFelice, M.S.

My experience in tracking results with typical families using quality enzyme supplements in daily life and following the guidelines developed for enzymes since 2001, show around 93 percent of all individuals across all age groups see success of some kind.

This means most people can see improvements by the time they get to the end of one bottle of a quality enzyme product.

You do not have to change any diet, supplement, medication, or therapy to try enzymes. One bottle, one month, and typically under $40—that is your investment in trying enzymes.

The following are typically reported improvements, often dramatic in degree, seen in both children and adults, when following the relatively new guidelines.

• Improvement in foods tolerated, eating patterns, and weight regulation
• Improvement in digestive function and bowel regularity
• Improvement in energy levels, stamina, and overall health
• Improvement in quality of sleep and moods
• Improvement in cognitive awareness, problem solving, and memory
• Improvement in language, socialization, and general behavior
• Improvement in transitioning, sensory processing, and attention
• Decrease in general anxiety, obsessive compulsions, and hyperactivity
• Decrease in acid reflux problems
• Decrease in autoimmune problems
• Decrease in chronic pain and joint stiffness
• Decrease in chronic viral-related problems
• Decrease in harmful bacteria and yeast problems

Another general improvement is that enzymes enhance the effectiveness of other supplements, diets, and therapies. You may see your overall program become much more effective when you start enzymes. Given how relatively inexpensive, easy to take, and fast acting enzymes are, it is generally worth at least a trial especially considering the wide range of potential improvements.

Many people find the longer they take enzymes, the fewer enzymes are needed to maintain the same level of health. Taking higher doses of enzymes for the first few months may improve health substantially so lower amounts of enzymes are necessary later. In addition, as the gut heals and the intestinal cells return to proper function, your own natural enzyme production improves. Various therapeutic enzyme programs have been extremely successful recommending high-doses of particular enzyme blends for designated periods of time, especially in the cases of persistent health problems. As with most measures, always consult with your health care professional whenever you have major health concerns.

Karen DeFelice, M.S. is the author of Enzymes: Go With Your Gut. DeFelice works in education and the sciences and is available for speaking, workshops, or teaching. www.enzymestuff.com.

Overview

Enzymes are substances that occur naturally in all living things, including the human body. If it’s an animal or a plant, it has enzymes. Enzymes are critical for life. At present, researchers have identified more than 3,000 different enzymes in the human body. Every millisecond of our lives these enzymes are constantly changing and renewing at an unbelievably fast speed.

Every life process depends on the action of enzymes, protein “go-betweens” that control the fueling and energy output of each cell in the body. Bodies rich in enzymes function at their best, with high energy levels, and full powers of disease resistance.

Each activity that occurs within the body involves enzymes. Examples include: 1) the beating of the heart, 2) the building and repairing of tissue, 3) the digestion and absorption of food. Nothing can take place without energy and energy cannot be used or produced without enzymes. Enzymes are involved in all bodily functions. In fact, the very existence of each living cell depends on complicated chemical reactions that require a constant supply of energy and enzymes. Without energy, cells become disorganized, resulting in illness and death. It is for this reason that the body’s energy needs to take precedence over all other body requirements.

Enzymes are very specific. Each enzyme promotes one type of chemical reaction and one type only. Some enzymes break down large nutrient molecules (the proteins, carbohydrates, and fats in our foods) into smaller molecules for digestion and aids the human body incorporating the raw material from food or supplements.

Without enzymes, our bodies cannot process and use the vitamins, minerals, and other nutrients present in our food and supplements. It is also important to remember enzymes are not nutrients themselves but rather work with the nutrition that is in the food or supplements you are consuming. Taking enzyme supplements does not replace a good healthy diet of quality food. Additional enzymes are responsible for different functions, such as the storage and release of energy or the processes of respiration, reproduction, vision, and others.

Without enzymes, none of the body’s chemical reactions would take place. Without enzymes, there would be no breathing, no digestion, no growth, no blood coagulation, no perception of the senses, and no reproduction. Our bodies contain trillions of enzymes, which continually renew, maintain, and protect us. No person, plant or animal could exist without them.

The body’s ability to function, to repair when injured, and to ward off disease is directly related to the strength and numbers of our enzymes. That’s why an enzyme deficiency can be so devastating.

It is the energizing, staying power of enzymes that helps start the day and keeps you going. Enzymes may be the way to recover faster from injuries, relieve back pain and circulation problems, and combat viruses.

Each process consists of a complex series of chemical reactions. These reactions are referred to as metabolism.

Metabolism includes all the physical and chemical processes involved in the activities of life. Enzymes are the catalysts that make metabolism possible. Consequently, enzymes are involved in every metabolic activity in the body—from digesting and assimilating food to catalyzing the thousands of reactions that are necessary for the body to function in the activities of life. Enzymes are the means within the cells by which the building-up and breaking-down processes of metabolism take place. Nature has devised a brilliant procedure to supply the constant demand for energy, called biologic oxidation.

Enzymes are involved in the synthesis and repair of DNA; in the production of proteins, and connective tissue necessary to grow and regenerate cells; and in the breakdown and detoxification of cellular wastes that are a by-product of normal metabolism.

This process allows us to obtain energy from food without burning up body tissue at the same time. Because of the catalytic activity of enzymes, food can be burned at low temperatures which are compatible with the life of the cell.

Because enzymes are catalysts, their effectiveness can be greatly influenced by their environment. An acid or alkaline environment will affect their activity, as will temperature, concentration of substrate (the substance upon which they work), coenzymes or cofactors, and inhibitors.

Cells obtain energy from the protein, carbohydrates, and fats we eat. They do this only with the assistance of enzymes. Before they reach the cell, all proteins are converted into amino acids, fats are converted into fatty acids, and carbohydrates are changed to sugars, such as glucose. The cells oxidize these nutrients, releasing large quantities of energy in the process. We need this energy to enable mechanical muscle movement and other body functions to occur. To produce this energy, chemical reactions must be “coupled” with the systems responsible for these physiological functions. This coupling is achieved through special energy transfer systems and cellular enzymes.

Enzymes are also important for your nervous system. Nervous system function is regulated by various neurotransmitters, such as serotonin, the catecholamines (dopamine and norepinephrine), and acetycholine. These neurotransmitters are manufactured by the action of enzymes in the brain on the precursor amino acids, tryptophan, tyrosine, and choline, respectively. Because the brain cannot make adequate quantities of the various precursors, it must obtain these precursors from the bloodstream.

However what if your digestive system hasn’t properly broken down the protein you eat into its component amino acids, thus leading to a deficiency state in your bloodstream?

Enzymes and Aging

As we grow older our bodies are faced with an array of age-related disorders. If you study societies as they age and their corresponding disease rates, you can see a clear parallel between increase in age and the occurrence of diseases.

Enzymes are the most powerful weapon we have against these diseases of age, and possibly a significant factor in avoiding age-related diseases.

The benefits of enzymes can be verified by solid scientific data, including clinical studies. We also know that systemic enzyme therapy is helpful in supporting the immune system and the immune system is affected by every disease.

Enzymes are active throughout and benefit the entire body, not just the immune system. Generally speaking, aging is a dehydration of the body’s protein supply–sometimes referred to as protein polymerization.

This is actually why we wrinkle as we age. These dehydrated proteins lose their flexibility, specifically under the skin. Proteases, such as those in systemic enzymes, hydrate the proteins by depolarizing them. This is a very important anti-aging mechanism and may actually prevent or repair the skin’s wrinkled look.

Taking protease enzymes orally may help reduce the pain, swelling and overall discomfort of varicose veins, phlebitis and post-thrombotic syndrome. Enzymes improve blood circulation and therefore reduce the risk of thrombosis.

With regular use of enzymes people can enjoy a better quality of life. As more of our aging population realizes the benefit of enzymes, more 90-year-olds will enjoy life in good health.

Life is aging and aging is a process. Aging is relative. Compared to the drosophila fly, the human life span is long; compared to the redwood tree, the human life span is short.

Aging is a variable parameter. The rate at which you age is determined by three factors: your genetic background, your life style and your nutritional habits. We can only influence aging by changing our life style and our nutrition.

Sources of Enzymes

Traditionally, foods have been the primary source. Uncooked foods (such as fruits and vegetables) are usually high in enzyme activity and, fortunately, taste good, too.

In theory, it works—absorbing enzymes from the food we eat. However, in practice, with the magnitude of food additives, preservatives, radiation, long-term storage, canning, freezing and drying, the actual enzymatic activity level of foods can be grossly reduced. Because of this there is an energy drain. As we age, the quantity of our body’s enzymes decreases and so does the quality. The speed with which this happens is greatly influenced by our life style and diet. An enzyme-poor diet can overtax an already deficient system.

The Solution

What’s the solution to an energy drain? Daily supplementation in addition to foods may ensure an adequate supply of enzymes.

We can’t produce energy without catalysts, and enzymes are those catalysts. You can’t jump start your day and feel young, with energy and vitality, if your body has lost its enzyme punch.

Life is similar to walking on a tightrope. Like everything else, there is a beginning and an end on the tightrope called life. As we move along on our journey, we must balance our bodies (this is known as homeostasis) or we can fall off the tightrope before our time, before reaching our scheduled end. This balancing act involves the total body (mind and spirit), yin and yang, temperature, pH, vitamins, minerals, anabolic-catabolic ratio, the oxidation of body cells, and importantly enzymes. All must be in harmony and enzymes help us maintain that balance.

Jump Start Digestion

Some people can eat nutritious foods and yet be continually tired, develop chronic diseases, and/or age prematurely.

Quite possibly it could be poor digestion and/or absorption of foods. In other words, an individual could be eating a healthy diet, but the nutrients aren’t getting to the cells. Literally, one can eat the best and yet the body is starving.

One way to support an overworked digestive system is to take natural digestive enzymes. Pepsin is probably the best known and is essential for protein digestion. Enzyme preparations contain many enzymes capable of breaking down proteins, fats, and carbohydrates. Some sources of digestive enzymes include papain, amylase, protease, and lactase.

Today’s scientific research indicates large enzyme molecules can be absorbed from the intestines, passing into the circulatory and lymphatic systems and, ultimately, to every cell of the body. For a long time people didn’t think we could absorb supplemental enzymes. We now know that we can absorb enzymes in a number of ways, primarily through a mechanism known as pinocytosis. Pinocytosis is actually a system whereby enzymes, after connection to a receptor in the mucosa of the intestinal wall, are absorbed into that wall, guided through the intestinal cells, and finally released into the blood, much like an elevator going from one floor to the next.

Researchers are now able to produce enzymes to treat specific acute and chronic disorders. This technique is called systemic enzyme therapy. Since many chronic disorders involve disturbed enzyme function, it seems logical to take supplemental enzymes.

It is also important to be apprised of the potency details of every individual enzyme so you know exactly what you’re getting. Enzyme strength is measured in terms of activity (not weight).

Enzymes may be present, but unless they are functional, they will not do any good. Instead of weight (such as milligrams) the important measurement with enzymes is the activity and potency of the enzyme. A product label should list enzyme strength in standard activity units rather than by weight.

DIGESTIVE ENZYMES

Digestive enzymes provide optimal support for healthy digestion of proteins, carbohydrates and fats.

Benefits of Microbial Enzyme Supplementation
Enzyme supplementation promotes enhanced digestion and delivery of vital nutrients to the body. This benefits good health in many ways, including better elimination, support for healthy energy levels and maintenance of healthy body weight. Enzymes also help prevent accumulation of undigested foods in the large intestine, which may disrupt the normal healthy bacterial balance in the bowel.

Overeating can lead to incomplete digestion. Occasional heartburn, bloating, belching, discomfort, and a “sour stomach” is often a result of this.

The nature of the digestive process in the human body is such that it is highly energy-intensive. The pancreas is the organ that produces most of the digestive enzymes required for food breakdown and secretes them into the small intestine. The lower the efficiency of digestion in the stomach, the higher the requirement of newly produced pancreatic digestive enzymes. This process can place a burden on the pancreas, which may, in turn, place a large burden on other parts of the body. If the pancreas is working overtime to support our body’s digestive process, it is diverting crucial resources from normal repair functions the body may need to perform in diverse organs and systems.

However, the body has developed a compensation method for dealing with this undue burden. The body smartly recycles enzymes that it produces as the unused portions enter the bloodstream into systemic circulation. Research has shown this recycling is facilitated by pancreatic secretory cells themselves. These cells, which normally secrete enzymes produced by the pancreas into the small intestine, serve as collectors of unused enzymes that are circulating in the bloodstream and can then re-secrete these enzymes into the intestines when needed for digestion. This reduces the burden on the pancreas to produce new enzymes in increasingly large amounts. What is most interesting, however, is research shows this mechanism is used by the body not only for the endogenous (produced by the pancreas) enzymes that are in circulation, but also for exogenous (i.e., supplemental) enzymes taken in from an outside source.

Supplementing with enzyme formulations containing a full-spectrum of digestive capacity, can reduce the need for the pancreas to manufacture enzymes and reduce the need for the body to devote large amount of resources for this purpose. This frees up the body to devote its energies to the daily maintenance of other critical bodily organs and systems, potentially maintaining and enhancing overall health.

Choosing a Digestive Enzyme Supplement

Microbial-derived enzymes have distinct advantages over animal-sourced enzymes such as pancreatin and have been shown to be more effective at supporting the digestive physiology of the human body when supplemented. Animal-derived standard enzyme preparations are active only in a narrow pH range and the activity of these enzymes is destroyed by acidic conditions in the stomach. By contrast, microbial-derived enzymes have higher activity levels (less enzyme has to be used for the same purpose) and are active over a wide pH range, with some reports showing activity from pH two to ten. This means while over 90 percent of animal-derived enzymes may be inactivated in the stomach and thus useless for digestive purposes, microbial-derived enzymes would begin digesting food in the acidic conditions of the stomach and continue this process well into the small intestine, increasing the efficiency of the digestive process.

Profile of Digestive Enzymes, which Provide Support or Carbohydrate and Fiber Digestion

Alpha-galactosidase—An enzyme that facilitates the breakdown of carbohydrates such as raffinose and stachyose. This enzyme is especially helpful in supporting the digestion of vegetables and beans. A study published in 1994 showed alpha-galactosidase supplementation was effective at reducing indigestion and flatulence in healthy individuals consuming a high-fiber diet consisting of grains, beans and other vegetables.

Amylase—This enzyme functions to break down carbohydrates such as starch and glycogen (rice and potatoes), a storage form of glucose.

Beta-glucanase—An important enzyme that facilitates the digestion of beta-linked glucose bonds associated with whole grains such as barley, oats and wheat.

Cellulase—This enzyme helps free the nutrients found in both fruits and vegetables by breaking down cellulose, a plant fiber.

Glucoamylase—This enzyme complements the function of amylase for the complete digestion of carbohydrate rich foods by further breaking down starches and dextrins into glucose.

Hemicellulase—This enzyme assists in the breakdown of carbohydrates (fruits) and is most useful for enhancing the efficiency of polysaccharide digestion from plant foods.

Invertase—This enzyme facilitates the breakdown of carbohydrates and is especially effective at helping to digest sucrose, common table sugar.

Lactase—This enzyme is necessary for the proper utilization and digestion of lactose, the predominant sugar found in milk and other dairy products.

Phytase— This enzyme (found in flax seed) breaks down plant carbohydrates and is especially helpful at breaking down phytic acid found in leafy vegetables. Because it breaks down phytic acid it frees the minerals in plants and aids in their absorption.

Xylanase—This enzyme is a sub-type of hemicellulase and functions to break down soluble fiber from food sources.

Support for Protein Digestion Bromelain—An enzyme that is derived from pineapple, this nutrient also facilitates the digestion of proteins. Bromelain has also been associated with the wide range of diverse health benefits on its own.

Papain—This enzyme is derived from papaya and serves to enhance the digestion of proteins, facilitating nutrient absorption.

Proteases—This grouping of enzymes support the digestion of protein and protein-containing foods, breaking them into absorbable units of amino acids, the building blocks for the body’s regenerative purposes.

Support for Fat Digestion
Lipase—The main enzyme that functions to break down lipids and improve fat utilization. In this capacity, it supports the function of the gall bladder. The microbial-derived lipase used in this formulation has been shown to have much higher activity levels than animal-derived lipase enzyme, enhancing the efficiency of fat digestion. Microbial lipase is resistant to inactivation by stomach acid and can digest dietary fat beginning in the stomach and continuing into the small intestine. A study in animals showed that microbial-derived lipase was as effective at digesting fat as a 25 times larger dose of conventional pancreatin.

PROTEOLYTIC ENZYMES

Proteolytic enzymes function throughout the body to digest and break down proteins into their amino acid components. When taken as supplements, studies show that various proteolytic enzymes, including bromelain (from pineapple), papain (from papaya), serratiopeptidase (from bacteria), and fungal protease (from a non-pathogenic fungus medium), are absorbed through the lining of the digestive tract and into the circulation. These enzymes, once in the bloodstream, are available to facilitate chemical reaction throughout the body and have a wide range of applications.

A potent, high-quality proteolytic enzyme formula should include a broad spectrum of proteolytic enzymes from a variety of plant, bacterial, and fungal proteases. The goal is to create a blend that works at a variety of pH levels to support the body’s native enzymatic needs. Maintaining optimal enzymatic function is a key factor in supporting the foundation for health and wellness of numerous individuals. For example:

Papain—A proteolytic enzyme derived from the sap (also called latex or milk) of unripe papaya, traditionally used with bromelain.

Fungal amylase—An enzyme derived from the fungus Aspergillus oryzae it breaks down carbohydrates, such as starch, and glycogen.

Lipase—The main enzyme responsible for breaking down fats, lipases hydrolyze triglycerides (fats) into their component fatty acid and glycerol molecules.

Protease (bacteria, fungal, neutral)—A group of enzymes whose catalytic function is to hydrolyze (breakdown) peptide bonds of proteins. Proteases differ in their ability to hydrolyze various peptide bonds. Bacteria proteases are optimally active in alkaline conditions, fungal proteases in more acidic conditions, and neutral proteases (from bacteria) are optimally active at a neutral pH.

Serratiopeptidase (aka Serrapeptase)—The “Miracle Enzyme” according to Dr. Hans Nieper, a legendary medical doctor known for his extensive use of proteolytic enzymes. This proteolytic enzyme has been shown to be more powerful than the pancreatic proteolytic enzymes chymotrypsin and trypsin. Serrapeptase appears to thin mucus and modulate molecules involved in both the immune and blood clotting systems. Studies thus far suggest Serrapeptase is a promising, safe and useful supplement to help support the immune system and thin mucus. Other double-blind studies have shown Serrapeptase supports the body’s immune response to infections and that it modulates the body’s immune response after surgery.

Bromelain—A general name for a family of proteolytic enzymes derived from the pineapple plant. Bromelain effects various systems in the body through a variety of physiological mechanisms, including inhibiting the formation of bradykinin, limiting the generation of fibrin, increasing the breakdown of fibrin, modulating prostaglandins, and decreasing platelet aggregation.

Nattokinase—This proteolytic enzyme is extracted from a Japanese food called Natto. Is has been identified to be a potent fibrinolytic enzyme, showing as ability to break down fibrin, a blood clotting protein. Supported by strong research and historical anecdotal use, Nattokinase shows promise in supporting areas such as cardiovascular well-being, stroke, angina, thrombosis, atherosclerosis, fibromyalgia/chronic fatigue, varicose veins, and other conditions of chronic inflammation.

totalhealth magazine is committed to keeping our readers up-to-date as more information is released on the benefits to human health of these and other existing or newly introduced enzymes. In the interim we suggest you seriously consider including digestive and proteolytic enzymes as an integral inclusion in your personal natural health regimen.

Dear Readers,

Welcome to the February 2019 issue of TotalHealthOnline Magazine. We wish everyone a Happy Valentines Day.

Charles K. Bens, PhD, in “Changing Your Age Equation” gives us a heads up with general strategies and to be adjusted based on factors such as age, sex, general health, metabolism, genetics and income. We all can only do the best that we can given our personal circumstances. Bens is clear on there being no excuse for not paying attention to the scientific facts that are included in this article.

“Stress Hormone #2—Insulin,” by Ann Louise Gittleman, PhD, CNS. Long-time weight loss, detox, and anti-aging expert alerts us that insulin is the one hormone that you have the most control over. It is controlled primarily by what you put in your mouth. All foods trigger a hormonal response. Gittleman shares details on how excess production of insulin can result in too much blood sugar being stored as fat, interfering with weight loss efforts. Another reminder on the influence of stress on the body.

Gene Bruno, MS, MHS, in “An Overview of Vitamin C.” This is one vitamin the human body is unable to make. The source of vitamin C is your diet and supplements. Broccoli and potatoes (not French fries) in addition to orange juice and grapefruit juice are good sources. There are some exceptions based on prescriptions you may be taking. Bruno also discuses dosages of supplements and where there may be restrictions. We always recommend consulting with your healthcare provider.

“BEMER For Circulation Health,” by Ross Pelton, RPh, CCN, recommends and discusses a product, which helps blood circulation, including even the tiniest vessels in the body. BEMER stands for Bio-Electro-Magnetic Energy Regulation. BEMER Pro is an FDA-approved Class 1 medical device that dramatically improves circulation to micro-capillaries throughout the body. BEMER is not a “therapy” for any disease or health condition. However, many functions in the body start to improve when cells receive more oxygen, more nutrients and generate more energy.

Gloria Gilbère, CDP, DAHom, PhD, offers “Menestra de Lentejas (Lentil Stew).” Another of Gilbère’s fabulous recipes from her test kitchen in Ecuador. “If you visit this unforgettable country (my new chosen homeland) of amazing people, spectacular scenery, celebratory festivals, diverse music, and colorful ancient customs, the one thing you’ll find everywhere is the national dish—menestra.” Menestra is made with lentils, you may also see it with chickpeas, red or pinto beans, it can be made with or without meat for vegetarians.

Shawn Messonnier’s, DVM, topic this month is “Liver Disease in Pets.” Beginning with, “liver disease is the catch-all term that is applied to any medical disorder affecting the liver and usually causing elevated blood levels of liver enzymes. It can be divided into both acute and chronic disease.” Read on for a thorough discussion of liver disease in pets. Thanks to you our readers, the authors and advertisers.

Best in health,

TWIP—The Wellness Imperative People

Click here to read the full February 2019 issue.

• Changing Your Age Equation
  Charles Bens, PhD
• Stress Hormone #2—Insulin
  Anne Louise Gittleman, PhD, CNS
• An Overview Of Vitamin C
  Gene Bruno, MS, MHS
• BEMER For Circulation
  Ross Pelton, RPh, CCN
• Menestra de Lentejas (Lentil Stew)
  Gloria Gilbère, CDP, DAHom, PhD
• Liver Disease In Pets
  Shawn Messonnier, DVM

Click here to read the full February 2019 issue.

Meditation, yoga, tai chi and other practices often are mentioned in passing as being good for health. However, it is surprising how little medical research has been devoted to testing such claims. Perhaps equally surprising is that until recently little work had been undertaken to quantify the impact of stress on aging. Of course, people often talk about reducing stress and note that too much stress is not good for us, but how much is too much and what, exactly, is the impact on the length of life? It took the interest of a Nobel Prize Winner finally to direct research at medical schools towards these questions. A paper by Epel and Blackburn on the impact of stress on the length of telomeres, a direct cellular measure of successful aging, only appeared in the Proceedings of the National Academy of Sciences in December 2004.¹ More than a decade later, meditation has begun to be accepted as a low cost /no cost approach to health benefits.

Stress and Adrenal Fatigue

In medical circles, two syndromes often are discussed with regard to what laymen consider to be the consequences of stress. The first is adrenal insufficiency. Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; it also may include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common. Adrenal insufficiency is a medical condition that requires intervention beyond dietary supplements.

Adrenal fatigue occupies a bit of a nether world in many medical circles, meaning that allopathic medicine is not quite sure that it is real. According to the Mayo Clinic, adrenal fatigue is a term often applied to a collection of nonspecific symptoms, such as body aches, fatigue, nervousness, sleep disturbances and digestive problems. However, it also is used as a catch-all for the exhaustion caused by placing demands upon the body that are beyond its normal recovery capacity. Very important in this picture is cortisol, a hormone manufactured in the adrenals, but also exhibits a metabolism that is regulated strongly in various peripheral tissues, such as in fat stores.

The counter-regulatory or "stress" hormone cortisol plays crucial everyday roles in the regulation of blood sugar levels, inflammation and the circadian rhythm. Cortisol should be relatively low late in the day as we unwind and prepare for sleep and should rise quite significantly starting an hour or two before waking. The circadian pattern of cortisol release generally is considerably more important than is its total 24-hour level.

Acute demands outside the normal range and chronic stress alter this picture. Recurrent increases in stress levels, both from psychological and physiological sources, can result in excess cortisol production or alterations in cortisol release timing leading to a disrupted homeostasis and directly affecting the hypothalamic-pituitary-adrenal (HPA) axis, the nervous system, and an array of other body systems.

Immediate responses to stress
Typical acute phase reactions to stress are increases in heart and respiratory rates, elevations in blood pressure and blood sugar, and a general increase in cellular metabolism.

Post-stress reactions
Those in good health, especially younger individuals, quickly recovery equilibrium. However, stress in excess of immediate recovery capacity can lead to bouts of hyperglycemia, fatigue, insomnia, irritability, anxiety, etc.

Poor recovery from stress
Chronic stress disrupts the normal equilibrium of the body. Chronic elevations of cortisol and the neurotransmitters epinephrine and norepinephrine initially cause people to feel energetic, yet unable to rest. Indeed, there is increasing dysregulation of an array of hormonal systems, including growth hormone, glucocorticoids, adrenocorticotropic hormone (ACTH), mineral corticoids, angiotensin, and others. Ultimately a number of vicious cycles can be set in motion. These include set points involving mineral corticoids and insulin. One example of this is a cycle involving blood sugar, insulin and cortisol:

chronic ↑ blood sugar => ↑ insulin + ↑ leptin => insulin resistance + leptin resistance => ↑ cortisol => ↑ blood sugar

Depending on the individual's starting constitution and habits, this can lead to elevations of blood sugar and lipids, water retention, mood swings, a loss of lean tissue followed by a gain in fat tissue, generalized fatigue and other symptoms.

The goal of any program aimed at controlling stress and reducing adrenal fatigue is to promote adaptation. One classic way of thinking about this issue is to consider the medical concept of allostasis, the process of achieving stability, or homeostasis, through physiological or behavioral changes. This can be carried out by means of alterations in HPA axis hormones, the autonomic nervous system, cytokines, or a number of other systems, and is generally adaptive in the short term. This adaptation calls upon mediators such as adrenalin, cortisol and other chemical messengers with the obvious corollary of increasing demands on precursor substrates and the production of downstream metabolites.

Repeated episodes of allostasis increase allostatic load. This means that repeated episodes of stress increase the demands that are placed on the body. Even the body's attempts at rebalancing can lead to cumulative damaging effects. The burden of the level of responses required either repeatedly or chronically itself becomes an insult (stressor) in its own right.^2,3

Meditation, Stress and Telomeres
The pioneering work of Epel and Blackburn linked perceived stress to shorter telomeres in healthy women as well as in Alzheimerfs caregivers, victims of domestic abuse and earlylife trauma, and people with major depression and posttraumatic stress disorder. Telomeres are a repeating DNA (deoxyribonucleic acid) sequence that "caps" or shields the ends of the chromosomes each time that cells divide and the DNA is copied. With successive cell divisions, the protective caps wear down. Blackburn received a Nobel Prize for discovering an enzyme called telomerase that can protect and rebuild telomeres. This enzyme slows the slide towards telomeres becoming too short to protect the chromosomes and leading to a loss of the ability of cells to divide. The length of telomeres thus is one measure of how many cycles the cells have left, a measure of aging. The key finding regarding stress and aging is that stress and our ability to cope with stress strongly affect telomere length. Subsequent work in other labs revealed that the stress hormone cortisol reduces the activity of telomerase. Oxidative stress and inflammation—the physiological fallout of stress—appear to erode telomeres directly.^4,5

There are various ways of attempting to control stress its negative effects, including exercise, social support groups, eating advice, and so forth. One of the most successful in trials is meditation. As reported in an excellent 2104 BBC review,⁶

In one ambitious project, Blackburn and her colleagues sent participants to meditate at the Shambhala mountain retreat in northern Colorado. Those who completed a three-month-long course had 30 percent higher levels of telomerase than a similar group on a waiting list. A pilot study of dementia caregivers, carried out with UCLA's Irwin and published in 2013, found that volunteers who did an ancient chanting meditation called Kirtan Kriya, 12 minutes a day for eight weeks, had significantly higher telomerase activity than a control group who listened to relaxing music. And a collaboration with UCSF physician and self-help guru Dean Ornish, also published in 2013, found that men with low-risk prostate cancer who undertook comprehensive lifestyle changes, including meditation, kept their telomerase activity higher than similar men in a control group and had slightly longer telomeres after five years.

Western style research thus increasingly is validating meditation as a tool for combatting known markers for aging. The next issue is whether meditation improves individual conditions, such as high blood pressure and high blood sugar.

Meditation and Specific Conditions
Telomere length and the production of telomerase to regenerate telomeres are indirect measurements of health. Impacts on these markers can suggest anti-aging benefits, but true clinical findings involve endpoints, not markers, i.e., were subjects followed long enough to demonstrate an actual increase in longevity? With long-lived animals such as human beings, this type of follow-through is difficult. However, meditation has been tested in regard to specific medical conditions, including blood pressure, blood sugar and mental aging. Results have been positive in all three.

Blood Pressure
Although statistical reviews typically have found that clinically meaningful changes in health related to blood pressure usually take place only when systolic blood pressure (SBP, the upper figure) exceeds 140 and diastolic blood pressure (DBP) exceeds 90, in recent years increasing attention has been paid to the category of prehypertension. Nearly 60 million Americans have blood pressure (BP) in the prehypertensive range (SBP of 120– 139 and/or DBP of 80–89). These numbers do not yet warrant medication, yet may signal that changes in diet, exercise and other habits should be undertaken to prevent the emergence of the clinical condition that does require treatment.

Mindfulness-based stress reduction (MBSR) is a change in habits that has been tested under controlled conditions. In a trial published in 2013, it involved body scanning exercises, sitting meditation and yoga exercises performed in eight supervised group sessions totaling 2½ hours per week. Subjects also were encouraged to practice at home. The trial examined 56 men and women averaging 50.3 years of age with BP in the prehypertensive range randomized to eight weeks of either MBSR or active control conditioning consisting of progressive muscle relaxation training (PMR) (the control arm).⁷

Patients in the MBSR group exhibited significant reductions in blood pressure measurements; systolic blood pressure decreased by an average of 4.8 millimeters of mercury (mm Hg) compared to 0.7 mm Hg with the control group, which did not receive the mindfulness intervention. Diastolic blood pressure also was lower in the mindfulness-based intervention group with a reduction of 1.9 mm Hg compared to an increase of 1.2 mm Hg in the control group.

Blood Sugar
As is true of blood pressure, in free-living populations meditation and other mind-body practices long have been associated with better body mass index and blood sugar regulation.⁸ Nevertheless, without prospective clinical trials, such benefits cannot be definitively claimed to be due to any given factor. Over the last handful of years, studies have gone some way towards remedying this issue.

In 2015, the Endocrine Society presented information on the effects of MBSR on fasting blood glucose in overweight and obese women. The NIH National Center for Complementary and Alternative Medicine (NCCAM) and the NIH National Center for Research Resources and the National Center for Advancing Translational Sciences funded the study.⁹ A pilot randomized controlled trial of 86 overweight or obese women (similar in age and body mass index) tracked eight weeks of either MBSR or health education control (HEC) with tests of fasting blood work and completed questionnaires at baseline, eight weeks and then at 16 weeks. The MBSR group's mindfulness scores significantly increased and its perceived stress scores significantly decreased compared to the HEC group's scores. Fasting glucose dropped significantly and quality of life improved significantly in the MBSR group, but not in the HEC group. Other measures were similar between the two groups.

Results with the MBSR intervention were good with regard to blood sugar just as with blood pressure. A different form of meditation may be even more successful. Traditional Buddhist walking meditation in a 2016 trial improved not only fasting blood glucose and blood pressure, but also glycosylated hemoglobin (HbA1c, a measure of long term blood sugar control) and other factors above the results found with walking alone in diabetic test groups.¹⁰ Twenty-three type 2 diabetics were split into two groups that performed a 12-week exercise program that consisted of walking on the treadmill at an exercise intensity of 50–70 percent maximum heart rate for 30 min/session, 3 times/week. In the Buddhism-based walking meditation exercise (WM) training program, the participants performed walking on the treadmill while concentrating on foot stepping by voiced "Budd" and "Dha" with each footstep that contacted the floor to practice mindfulness while walking.

Both arms in this trial improved. After 12 weeks, maximal oxygen consumption increased and fasting blood glucose level decreased significantly in both groups. In contrast, walking meditation exceeded simple treadmill exercise in other areas. There were significant decreases in HbA1c and both systolic and diastolic blood pressure only in the WM group. Again, arterial stiffness was improved only in the WM group and blood cortisol levels were reduced only in the WM group.

Brain Aging
Another area, one that concerns all of us who are getting a bit older, is brain aging. Observational studies and a number of studies have indicated that meditation can exert a positive influence, yet the question of "how" remains poorly determined. Does it involve telomeres, inflammation, stress regulation, macroscopic brain anatomy or other mechanisms? Answers suitable to the Western allopathic medical model only now are beginning to be uncovered.

A review published in 2017 attempts to survey the relevant issues.¹¹ It judges that "preliminary evidence for possible age-defying effects of meditation mostly stems from cross-sectional studies and/or from using indirect markers associated with aging. In contrast, controlled longitudinal studies between meditation and diminished brain aging are still missing." Nevertheless, "[w]ithout a doubt, the accumulating scientific evidence is very encouraging, especially given that meditation is relatively easy to integrate in everyone's every-day life."

Conclusions
A philosophical person—a lover of wisdom—indulges his appetites neither too much nor too little, but just enough to lay them to sleep and prevent them from interfering with higher activities. He collects himself in meditation to pursue spiritual investigations, seeking and discovering unrealized realities of the past, present, and future. Through identifying with his Higher Self in meditation he avoids being the victim of fantastic and uncivilized vagaries and most effectively attains Truth.

We tend to think of meditation as an "Eastern" tradition, but, in fact, very similar practices existed in the ancient Greco-Roman world until the closure of the Platonic Academy in 529 AD by Justinian I. A major goal of meditation is to attain inner balance neither by indulging the passions nor by stifling them. Many different techniques exist. Overall, the goal of classic meditation exercises was and remains spiritual benefit. Modern research has discovered that even those not directly interested in religious or philosophical paths can obtain quite real and tangible benefits from meditative practices. These benefits include stress reduction, a balancing of blood pressure and blood sugar and, perhaps, greater longevity.

References:

1. 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 USA. 2004 Dec 7;101(49):17312–5.
2. McEwen BS, Seeman T. Protective and damaging effects of mediators of stress. Elaborating and testing the concepts of allostasis and allostatic load. Ann N Y Acad Sci. 1999;896:30–47.
3. McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol. 2008 Apr 7;583(2–3):174–85.
4. Marchant J. Can Meditation Help Prevent the Effects of Aging? July 1, 2014. http://www.bbc.com/future/story/20140701-canmeditation- delay-ageing
5. Epel E, Daubenmier J, Moskowitz JT, Folkman S, Blackburn E. Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Ann N Y Acad Sci. 2009 Aug;1172:34–53.
6. Marchant (op. cit.)
7. Hughes JW, Fresco DM, Myerscough R, van Dulmen MH, Carlson LE, Josephson R. Randomized controlled trial of mindfulness-based stress reduction for prehypertension. Psychosom Med. 2013 Oct;75(8):721–8.
8. Younge JO, Leening MJ, Tiemeier H, Franco OH, Kiefte-de Jong J, Hofman A, Roos-Hesselink JW, Hunink MG. Association Between Mind-Body Practice and Cardiometabolic Risk Factors: The Rotterdam Study. Psychosom Med. 2015 Sep;77(7):775–83.
9. The Endocrine Society. "Stress reduction may reduce fasting glucose in overweight and obese women." ScienceDaily, 6 March 2015. www.sciencedaily.com/releases/2015/03/150306181815.htm
10. Gainey A, Himathongkam T, Tanaka H, Suksom D. Effects of Buddhist walking meditation on glycemic control and vascular function in patients with type 2 diabetes. Complement Ther Med. 2016 Jun;26:92–7.
11. Kurth F, Cherbuin N, Luders E. Promising Links between Meditation and Reduced (Brain) Aging: An Attempt to Bridge Some Gaps between the Alleged Fountain of Youth and the Youth of the Field. Front Psychol. 2017 May 30;8:860.
12. An admittedly idiosyncratic, yet helpful translation found at http://www.hermes-press.com/meditation0.htm

For the last billion years or so life on planet Earth has evolved with remarkable diversity, filling every niche, even those that seem unlivable. Included within this diversity of life are creatures that are essentially immortal, for example, the hydra, a fresh-water polyp that can live as long as 1400 years¹. Even more incredible is an immortal jellyfish² (Turritopsis dohrnii) that potentially, has been alive for the last 65 million years! If they had a memory, they could tell us what wiped the dinosaurs out! Recently, researchers re-animated a Bdelloid rotifer, a tiny animal that had been frozen in the Siberian permafrost for more than 24,000 years³.

Yet, for mammals, lifespan is much shorter. Human beings have a potential lifespan of more than 120 years⁴ which is much shorter than the amazing animals mentioned above but is still remarkable when others, like the common mouse gets only three years⁵. This hardly seems fair to the humble house mouse when its distant relative, the naked mole rat gets closer to 30 years⁶.

Can we change the speed we age?
The deeper you look the clearer it becomes that just like the diversity of life there is a diversity of longevity. And with that realization researchers have rushed to investigate the difference between short and long-lived species to identify and perhaps even develop interventions translating the lessons we learn from research and harnessing them to prolong the years we spend youthful and healthy on this planet.

In 2013 scientists published a paper called the Hallmarks of Aging in a research journal called Cell⁷. This paper identified nine hallmarks or causes of aging that ranged from DNA damage to mitochondrial dysfunction to cellular senescence. Each hallmark qualified as being involved in aging by the results of laboratory experiments. If you made a hallmark worse, it accelerated the aging process and if you protected it, you slowed down the aging process. This paper was important because it gave researchers targets to investigate to see if they could impact aging, and in so doing, they unleashed a phenomenal level of research to find compounds that positively affect each hallmark. And the size of the prize is huge. When a company solves the question of slowing the aging process, it will disrupt a trillion-dollar industry and give birth to a brand new one overnight.

Measuring the speed at which we age
Recently researchers have discovered that we have a biological clock that sits on our DNA with time being recorded by the number of methyl groups attached to our DNA⁸. Using machine learning they identified patterns of methylation that are closely correlated with our chronological age. And in the process discovered that different people age at different speeds not just outwardly but on the inside as well, and measurably so by looking at their DNA methylation patterns. Of course, we already knew that people age at different rates because we see some people fit and healthy into the 10th decade whereas some are not so lucky and seem to get the diseases of old age as early as their 5th decade. But to have a simple test to confirm this and allow people to assess the age their cells are acting compared to their chronological age is an incredible breakthrough.

What is exciting is that your biological age does not need to be your destiny and can be changed. If you have turned 50 and your DNA methylation is at a level that is usually seen with someone in their 70s then by making lifestyle changes like exercise and diet and taking new supplements you can bring your biological age into line with your chronological age. And perhaps even more exciting is that if your results are similar you can take the same actions to slow down your biological aging. It is entirely possible in your chronological 50s or 60s that you could celebrate your 40th or 30th decade again! And it is available to everyone, today, right now with simple actions.

Moving from luck to strategy in aging
For the first time in human history we are about to take the luck out of getting old with health and vitality and make healthy aging with an extended healthspan accessible to us all. In my book, "Harnessing the Nine Hallmarks of Aging," I have distilled the very latest in research and created a lifelong healthy aging plan for people who want to age better and arrive at a more mature age with more health and vitality than any previous generation of humans have obtained. I describe specific strategies for those who are in their 30s, 40s, 50s and beyond and share breakthroughs in our understanding of what molecules and supplements can impact and slow the aging process.

For example, molecules like Hobamine (2-HOBA)⁹, an extract from Himalayan Tartary Buckwheat, has recently been isolated and shows incredible potential to slow the aging process by protecting our delicate DNA and other cellular components and machinery from the damage associated with oxidative stress throughout our lifetime. Also, NAD, nicotinamide adenine dinucleotide, is an important co-enzyme that fuels our mitochondria and our cellular repair and maintenance mechanisms. NAD levels decline in our cells as we age, so by restoring this vital co-enzyme via supplements like NMN¹⁰ (nicotinamide mononucleotide) researchers have seen changes in our cells that are associated with levels of health seen in cells that are considerably younger.

In the future, there will be significant advances in our ability to slow the aging process beyond what we have available to us today. For now however, adopting the strategies outlined in "Harnessing the Nine Hallmarks of Aging" will help you slow the speed of aging that your cells experience, and with this you are taking affirmative action to delay the diseases associated with old age. The sooner you start the better shape your cells will be in and this will be reflected in how you feel, how you look and increase your healthspan - the amount of time you spend in your body while experiencing amazing health.

1. This Tiny Animal Can Live an Estimated 1,400 Years - Scientific American
2. Science of the immortal jellyfish, Earth's longest living animal - Science Focus
3. A living bdelloid rotifer from 24,000-year-old Arctic permafrost - ScienceDirect
4. Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit | Nature Communications
5. House mouse (Mus musculus) longevity, ageing, and life history - senescence.info
6. Naked mole rat may hold the secret to long life - phys.org
7. The Hallmarks of Aging: Cell
8. Epigenetic clock - Wikipedia
9. 2-hydroxybenzylamine - Search Results - PubMed
10. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice - nih.gov
11. Fisetin is a senotherapeutic that extends health and lifespan - PubMed
12. Senolytics reduce coronavirus-related mortality in old mice | Science
13. COVID-FISETIN: Pilot in SARS-CoV-2 of Fisetin to Alleviate Dysfunction and Inflammation - ClinicalTrials.gov

This article is the fourth in the series that began with “Solving the Mystery of the Multivitamin.” The focus now shifts to reasons for taking a multivitamin/mineral as we enter the second half of life and, more importantly, the overall approach to nutrition that should inform any anti-aging program. Readers will discover that some, but not all of the gender-specific nutritionaln needs covered in earlier articles become less meaningful in later life. As individuals approach 60, overall physiology changes in ways that tend to lead to a convergence of nutritional requirements.