• The President’s Desk  — Bill Threatens Health Freedom

• Healthy Aging  — Four Keys to Successful Weight Management

• LDL Oxidation  — The Smoking Gun Behind Heart Disease?

• Adrenal Fatigue  — Natural Support for Burned Out Adrenals

• Inflammation  — Its Cognitive-Destroying Effect

• Pet Corner  — Which Fatty Acids Are the Best for Pets?

• Digestive Health:  — Natural Support for E. Coli, H. Pylori and Other Digestive Concerns

• Vitamin D Important for Colon Health  — 
• Evidence Supports Adaptogenic Botanicals for Stress  — 
• Natural Immune Modulator Supports the Health of Allergy Sufferers  — 
• Low Omega-3 Fatty Acids Associated with Aging  — 
• Antioxidant Supports Healthy Lipids  — 
• More Research Supports Green Tea Intake  — 
• Vitamin Deficiency Associated with Increased Fat Deposition  — 

• Joint Support
• Menstrual Issues
• Fibromyalgia
• Shingles
• Folliculitis
• Anxiety
• Vitamin D Optimal Levels
• ADD, Kidney Stones
• Interstitial Cystitis
• Heart Health
• Hormonal Balance
• Thyroid Nodules

Once again, Congress is mounting an attack against dietary supplements by introducing a bill that purports to help monitor supplements’ “safety,” a bill that makes this industry a scapegoat for steroid use by professional athletes. If passed into law, “The Dietary Supplement Safety Act of 2010” will dramatically limit your access to safe dietary supplements.

Introduced by Republican Senators John McCain and Byron Dorgan, S. 3002 was crafted under the guise of supplement safety in order to hide its flaws. First, the bill is regulatory overkill, threatening existing legislation, namely the Federal Food, Drug, and Cosmetic Act and the 1994 Dietary Supplements and Health Education Act (DSHEA), which already ensure dietary supplements’ safety.

Another flaw? The bill overestimates the occurrence of steroid contamination in dietary supplements. The National Football League and Major League Baseball support the bill after Senator McCain said one of the bill’s purposes was to combat sports supplements contamination. However, the dietary supplement industry shouldn’t be blamed because sporting regulatory bodies have failed to correct their drug testing policies. Why should millions of Americans who safely and successfully use supplements be punished for sports leagues’ inefficiencies?

Third, this legislation places new burdens on dietary supplements not required for any other food. It requires companies to report non-serious adverse events to the Food and Drug Administration (FDA), which could stretch the FDA’s resources beyond the breaking point. The FDA would be buried under an avalanche of non-serious events, while serious event reports would be lost in the shuffle.

Instead of creating a new law blocking consumers’ access to safe nutritional supplements, why not enforce existing laws and regulations? In the 15 years since its passing, DSHEA hasn’t been adequately enforced. Furthermore, the recent implementation of Good Manufacturing Practices (GMPs) already helps ensure nutritional supplements’ safety. Our company has even taken GMPs one step farther, obtaining NSF sports registration guaranteeing our facility will produce products free from contaminants banned due to drug-testing criteria.

I urge you to contact your Senators today. Ask them to vote against senate bill S. 3002.

In the January issue of the newsletter I began a series of articles addressing the most critical health concerns as we age and my recommended protocols. In this issue, I will discuss a topic that is relevant to many of us as the summer bathing suit season approaches: weight management.

Yet, weight gain is more than a cosmetic issue. Elevated body mass index is a major risk factor for chronic diseases such as cardiovascular disease (mainly heart disease and stroke), diabetes, musculoskeletal disorders (especially osteoarthritis) and some cancers (endometrial, breast and colon).¹

The key to successful weight loss revolves around finding the cause—or causes—of the weight gain. In my clinical experience I have found that when excess fat stubbornly refuses to go away it is often caused by one or more of the following factors: 1) Imbalanced leptin and adiponectin levels combined with insulin resistance; 2) A tendency to put on pounds in the abdominal region (visceral fat); 3) High cortisol levels due to chronic stress; and/or 4) Low thyroid function (hypothyroidism).

In this article, I will discuss each of these causes of weight gain and offer strategies for addressing these four factors that are crucial to weight management.

Leptin: The Appetite-Regulating Hormone

Adipocytes (fat cells) synthesize and secrete leptin. Leptin’s presence in blood serum occurs proportionately to the amount of adipose (fat) tissue because fat cells, as they become enlarged in obesity, secrete more leptin.

This important hormone normally communicates with the central nervous system to regulate energy intake and energy stores in the body so that the hypothalamus can efficiently maintain a stable body weight. Leptin suppresses food intake² and increases thermogenesis³ and metabolic rate.⁴ Evidence also exists that leptin can mimic some of insulin’s actions. Accordingly, leptin increases glucose uptake in skeletal muscle and adipose tissue in vivo,^5-6 and normalizes blood glucose levels in diabetic rats.⁷ Leptin works together with insulin to influence appetite regulatory pathways in the hypothalamus.⁸

Due to leptin’s important role in appetite regulation, one would think that it would be desirable to increase leptin levels. However, in most overweight people, levels of this hormone are actually excessively high due to leptin resistance, a process similar to insulin resistance, where the leptin receptors become desensitized to leptin’s effects, causing the body to produce more and more of the hormone.

C-reactive protein (CRP), an inflammatory marker, plays a role in this process. During in vitro and animal studies, scientists have discovered a “vicious circle” whereby abnormally high concentrations of leptin as occurring in leptin resistance can propagate CRP expression. As a result, in obesity, the satiety signal never gets triggered because CRP binds leptin and prevents it from crossing the blood-brain barrier to suppress appetite. Thus, even though blood levels of leptin may be excessively high, brain levels are insufficiently low, resulting in food cravings and weight gain. By blocking leptin’s physiological functions, CRP represents a powerful component in the progression of leptin resistance and escalating weight gain.⁹

Leptin levels tend to rise as we age, one possible reason why individuals under 30 have an easier time losing weight than people who are in their 40s and beyond. Furthermore, estrogen deficiency as seen in menopause is related to a rise in leptin, offering a potential explanation for why women gain weight more easily after menopause.¹⁰

Leptin may also be the reason for a common challenge among dieters—regaining back the weight lost. Persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight, causing the vicious cycle to start again, whereby the excess weight causes higher levels of leptin production and leptin resistance.¹¹ This indicates the importance of making sure that leptin levels in the body are balanced at the proper level rather than simply trying to reduce its production altogether.

Adiponectin is another important player in weight loss. Like leptin, adiponectin is an anti-inflammatory, insulin-sensitizing and heart protective adipocytokine (a cytokine secreted by the fat cells) that plays a fundamental role in helping the body burn fat.

Adiponectin only recently emerged on the radars of scientists. After the year 2000, following extensive developments in the field of genetics, researchers determined that adiponectin was strongly connected with insulin sensitivity. They found that adiponectin was dramatically decreased in patients with excess fat mass. This same decrease in adiponectin was reported with insulin resistance and metabolic syndrome, a cluster of metabolic abnormalities classified as elevated triglycerides, reduced HDL cholesterol, hypertension, and high blood sugar. In fact, variations in genes associated with adiponectin were linked to development of the metabolic syndrome. Furthermore, it has been clearly demonstrated that adiponectin is an insulin-sensitizing cytokine and is therefore crucial to the body’s ability to use insulin effectively.¹²

At the same time that adiponectin has an effect on insulin, insulin also has an effect on adiponectin. It has been shown that high insulin levels down-regulate adiponectin receptor expression in non-obese women with polycystic ovary syndrome, resulting in adiponectin resistance.¹³

High-fat diets also can interfere with adiponectin’s insulin-sensitizing ability by altering skeletal muscle lipid metabolism. An imbalance between fatty acid uptake and oxidation results in intramuscular fat accumulation, which can impair the insulin-signaling cascade. Adiponectin stimulates skeletal muscle fatty acid oxidation and reduces fat accumulation. However, animal studies have shown that this beneficial effect is lost after high-fat feeding.¹⁴

In obesity and diabetes, low adiponectin levels are thought to exacerbate the pro-inflammatory state by inducing production of C-reactive protein.¹⁵

Maintaining balanced levels of leptin and adiponectin is one of the most important ways to maintain a healthy weight. Consequently, in my clinical practice I am now able to have my patients use a new supplement formulated to balance both leptin and adiponectin levels. In one interesting 8-week double-blind, placebo-controlled study, University of Connecticut researchers investigated the effect of this supplement in 22 women. One group of women consumed the supplement, which contained modified cellulose and cetylated fatty acids, while another group consumed a placebo. Both groups were put on identical exercise programs and dietary regimens. In the women who received the supplement, significant decreases occurred in body weight, percent body fat, leptin and insulin levels compared to the placebo group. Adiponectin levels, meanwhile, increased.¹⁶ Animal studies with this supplement have achieved similar results and I expect this to be a very valuable tool in my practice.

Visceral Fat

Visceral fat is very dense and is found deep within the abdomen, encasing the intra-abdominal organs. It is the reason why two people can weigh exactly the same amount yet one person—the person with the greater amount of visceral fat—is at greater risk for the metabolic syndrome, premature aging and death.

I find that visceral fat is a serious concern among many of my patients and since high levels of visceral fat are tied to the metabolic syndrome addressing this issue is critical. Researchers have indicated that the metabolic syndrome “might be considered a fatal consequence of visceral obesity.”¹⁷ Persons with metabolic syndrome have twice the risk of dying from all causes of death and three times the risk of having a heart attack or stroke compared with persons without metabolic syndrome.¹⁸

Losing visceral fat, therefore, is more than just a cosmetic issue—it’s a matter of life or death.

One common trend I see in my patients is that as they age, visceral fat increases. This is because, as we age, fat becomes dysfunctional and is redistributed from the less harmful subcutaneous fat under the skin to intra-abdominal visceral deposits.¹⁹ Once this happens, it is particularly destructive to the body as visceral fat cells release inflammatory substances such as C-reactive protein and Interleukin (IL)-6.²⁰

I recommend to my patients who are concerned about visceral fat to undertake a two-step approach. First, increase aerobic exercise. Second, utilize the flavonoid glabridin, which can be especially helpful in reducing visceral fat.

In one recent randomized, double-blind, placebo-controlled study, 81 healthy, moderately overweight subjects aged 40-60 years were randomly divided to 1 of 4 groups: 1) 3 placebo capsules per day (placebo group); 2) 1 capsule of a flavonoid oil containing glabridin (300 mg) and 2 placebo capsules per day (low-dose group); 3) Two capsules of the glabridin-containing oil (600 mg) and 1 placebo capsule per day (middle-dose group); or 4) 3 capsules of the glabridin-containing oil (900 mg) per day (high-dose group).

The results indicated that body weight and BMI (body mass index) were significantly lower than at baseline at 4 and 8 weeks in the high-dose glabridin oil group. The researchers also noted slight decreases in the low-dose and middle-dose groups. An increase in body weight and BMI was observed in the placebo group. At 8 weeks, total body fat mass was significantly lower compared to the study’s start in all 3 glabridin oil groups, but not in the placebo group. Visceral fat at 8 weeks was significantly lower than at baseline only in the high-dose group. Furthermore, low-density-lipoprotein cholesterol and total cholesterol were significantly lower at 8 weeks than at baseline in the high-dose glabridin group. The subjects achieved these results even though food intake did not change significantly during the study.¹⁸

The study authors concluded that the glabridin-containing oil “may...prevent or ameliorate obesity” and may “prevent obesity-induced metabolic syndrome, when combined with lifestyle modifications including moderate calorie restriction and moderate exercise.”

In some cases I may add a third step approach to weight loss by suggesting a supplement designed to balance leptin and adiponectin levels, as mentioned above.

Chronic Stress and Weight

For individuals who have a hard time losing weight or reach a plateau, chronic stress is often the problem. The high cortisol levels that occur when the body is under increased stress can lead to the accumulation of visceral fat.²¹ Furthermore, chronic stress can lead to overeating and suppression of certain anabolic hormones.²²

Researchers also have connected the dots between high cortisol levels and the metabolic syndrome. Both the metabolic syndrome and high cortisol levels share common characteristics, suggesting that the pathogenesis of metabolic syndrome and central obesity might involve prolonged and excessive exposure to cortisol. Cushing’s syndrome, a disease marked by high cortisol levels, shares many of the characteristics of metabolic syndrome.²³

A group of researchers searched publications during the last 20 years regarding the possible role of cortisol in the development of metabolic syndrome. They found that emerging data suggest that patients with metabolic syndrome show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a state of “functional hypercortisolism.” The increased exposure to cortisol contributes to increased fat accumulation in visceral depots.²³

Due to this link between cortisol and fat accumulation, controlling cortisol levels is of the utmost importance in a weight loss regimen. It is useful to measure levels of this hormone to get an idea whether disrupted cortisol levels are the primary reason for a patients’ weight gain. In my practice, I often recommend my patients use the adrenal function panel salivary cortisol test, which is available here.

If the results of the test reveal that cortisol levels are abnormal, I typically recommend my patients supplement with a combination of Eleutherococcus senticosus, Manchurian thorn tree (Aralia manchurica), astragalus (Astragalus membranaceus), ashwagandha (Withania somnifera) root and Schisandra chinensis, which are all found in AdaptaPhase^® I. These adaptogenic botanicals can support the adrenals, promoting balanced levels of cortisol.^24-26

I have found that in patients with high cortisol levels combining AdaptaPhase^® I with the Cortisol Control formula and Phosphatidylserine 100 Plus provides a strong foundation for optimal weight loss goals.

Hypothyroidism

Among my patients, I have noted that one of the common reasons for weight gain or the inability to shed pounds is hypothyroidism. Reports in the medical literature also indicate that even modest increases in serum TSH concentrations, higher levels of which are associated with hypothyroidism, may be associated with weight gain.²⁷

Therefore, I recommend that patients who have weight concerns visit with their physician to have their free T3 and free T4 tested along with TSH. Additionally, I recommend patients take an iodine sufficiency test (available here) since low levels of iodine are often implicated in hypothyroidism. The iodine sufficiency test was created as a tool to determine the proper dosage of iodine.

If the test results warrant, I then have my patients consume a special form of iodine known as Iodoral^®. In patients whose weight gain is caused by low thyroid function, combining Iodoral^® with ATP Cofactors can have excellent results. This program should always be undertaken under the guidance of one’s health care provider.

Conclusion

Successful weight management involves finding the primary reason behind the weight gain and undertaking a supplement regimen together with lifestyle changes to address that reason. In some cases, the weight gain may be due to more than one reason and in that case one can address multiple factors. The most successful strategies for weight loss may include balancing leptin and adiponectin levels, reducing visceral fat accumulation, helping the body cope with stress and ensuring the thyroid is functioning properly. Addressing the most relevant factor or factors while undertaking an exercise program and consuming a healthy diet can yield highly favorable results.

References

1. World Health Organization Fact Sheet. Available online at http://www.who.int/mediacentre/factsheets/fs311/en/index.html.
2. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL., Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995 July 28;269(5223):543-546.
3. Stehling O, Döring H, Ertl J, Preibisch G, Schmidt I. Am. J. Leptin reduces juvenile fat stores by altering the circadian cycle of energy expenditure. Physiol. 1996 December; 271(6 Pt 2):R1770-R1774.
4. Levin N, Nelson C, Gurney A, Vandlen R, de Sauvage, F. Decreased food intake does not completely account for adiposity reduction after ob protein infusion. Proc. Natl. Acad. Sci. U.S.A. 1996 February 20;93(4):1726-1730.
5. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 1997 September 25;389(6649): 374-377.
6. Yaspelkis BB, 3rd, Ansari L, Ramey EL, Holland GJ, Loy SF. Chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport. Metabolism. 1999 May;48(5):671-676.
7. Chinookoswong N, Wang JL, Shi ZQ. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes. 1999 July;48;1487-1492.
8. Kalra SP, Kalra PS. Neuropeptide Y: a physiological orexigen modulated by the feedback action of ghrelin and leptin. Endocrine. 2003;22(1):49-56.
9. Chen K, Li F, Li J, Cai H, Strom S, Bisello A, Kelley DE, Friedman-Einat M, Skibinski GA, McCrory MA, Szalai AJ, Zhao AZ. Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med. 2006 Apr;12(4):425-32.
10. Ainslie DA, Morris MJ, Wittert G, Turnbull H, Proietto J, Thorburn AW. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Int J Obes Relat Metab Disord. 2001 Nov;25(11):1680-8.
11. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS. Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med. 2010 Jan 19;152(2):93-100.
12. Vasseur F. Adiponectin and its receptors: partners contributing to the “vicious circle” leading to the metabolic syndrome? Pharmacol Res. 2006 Jun;53(6):478-81.
13. Seow KM, Tsai YL, Juan CC, Lin YH, Hwang JL, Ho LT. Omental fat expression of adiponectin and adiponectin receptors in non-obese women with PCOS: a preliminary study. Reprod Biomed Online. 2009 Oct;19(4):577-82.
14. Mullen KL, Pritchard J, Ritchie I, Snook LA, Chabowski A, Bonen A, Wright D, Dyck DJ. Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high-fat-fed rats. Am J Physiol Regul Integr Comp Physiol. 2009 Feb;296(2):R243-51.
15. Devaraj S, Torok N, Dasu MR, Samols D, Jialal I. Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells: evidence for an adipose tissue-vascular loop. Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1368-74.
16. Fragala MS, Kraemer WJ, Volek JS, Maresh CM, Puglisi MJ, Vingren JL, JY Ho,. Hatfield DL, Spiering BA, Forsythe CE, et. al. Influences of a dietary supplement in combination with an exercise and diet regimen on adipocytokines and adiposity in women who are overweight. Eur J Appl Physiol (2009) 105:665-672.
17. Scaglione R, Di Chiara T, Cariello T, Licata G. Visceral obesity and metabolic syndrome: two faces of the same medal? Intern Emerg Med. 2009 Dec 9. Published Online Ahead of Print.
18. Tominaga Y, Nakagawa K, Mae T, et al. Licorice flavonoid oil reduces total body fat and visceral fat in overweight subjects: a randomized, double-blind, placebo-controlled study. Obes Res Clin Pract. 2009;3:169-178.
19. Sepe A, Tchkonia T, Thomou T, Zamboni M, Kirkland JL. Aging and Regional Differences in Fat Cell Progenitors - A Mini-Review. Gerontology. 2010 Jan 29. Published Online Ahead of Print.
20. Arsenault BJ, Cartier A, Cóté M, Lemieux I, Tremblay A, Bouchard C, Pérusse L, Després JP. Body composition, cardiorespiratory fitness, and low-grade inflammation in middle-aged men and women. Am J Cardiol. 2009 Jul 15;104(2):240-6.
21. Mann JN, Thakore JH. Melancholic depression and abdominal fat distribution: a mini-review. Stress. 1999 Aug;3(1):1-15.
22. Epel ES. Psychological and metabolic stress: a recipe for accelerated cellular aging? Hormones (Athens). 2009 Jan-Mar;8(1):7-22.
23. Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab. 2009 Aug;94(8):2692-701.
24. Upton R, ed. Schisandra Berry: Analytical, quality control, and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999;1-25.
25. Lee S, Kim DH, Jung JW, et al. Schizandra chinensis and Scutellaria baicalensis counter stress behaviors in mice. Phytother Res 2007 Dec;21(12):1187-92.
26. Martinez B, Staba EJ. The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats. Jpn J Pharmacol 1984 Jun;35(2):79-85.
27. Fox CS, Pencina MJ, D’Agostino RB, Murabito JM, Seely EW, Pearce EN, Vasan RS. Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Arch Intern Med. 2008 Mar 24;168(6):587-92.

Cholesterol, which is known to be associated with the formation of atherosclerosis and plaque in arteries, is actually an important component of the structure of our cells¹ and even contributes to the formation of many hormones in the body. While it is clear that cholesterol provides a critical component to many tissues, high cholesterol’s link to atherosclerosis indicates cholesterol levels that are too high may pose a problem. The medical literature is now suggesting, however, that elevated cholesterol is not the sole link to formation of atherosclerosis and artery blocking plaque.²

Most of us are familiar with HDL, known as “good” cholesterol and LDL, known as “bad” cholesterol. Part of the reason that HDL is known as “good” cholesterol is that it carries an antioxidant enzyme (HDL-PON), which helps in cell repair and preventing the oxidation of cholesterol.³ While research shows that LDL cholesterol is a major risk factor for developing atherosclerosis, there is new information that suggests it is the oxidized form of LDL (oxLDL) that appears to be a significant trigger in the chain of events that accelerates atherosclerosis and plaques in the arteries.^4-6

How LDL Becomes Oxidized

Cholesterol is formed primarily in the liver, although some cholesterol is derived from the intestine from the ingested dietary fats, proteins and carbohydrate food sources. Cholesterol is then transported through the blood to different tissues. As cholesterol is a form of fat, it does not dissolve in water, so for transport in the blood to occur cholesterol needs to be coated with a thin lipid and protein coat, called a lipoprotein, to allow it to be transported. There are 5 major classes of lipoproteins, such as the low density lipoprotein (LDL) and high density lipoprotein (HDL), both of which carry cholesterol through the blood. The LDL and HDL carriers of cholesterol are the most commonly monitored components of cholesterol in regard to health.

LDL is associated with bringing cholesterol to cells that need cholesterol for repair and maintenance of cell membranes. HDL carries cholesterol away from the cells and back to the liver. Inside the arteries, it turns out that the scavenger cells known as monocytes and macrophages play an important role in carrying the cholesterol from the cells lining the arteries and turning it over to the HDL for the return trip to the liver. Because both HDL and LDL contain lipids in addition to their protein components, both are susceptible to free radical damage that causes oxidation of the lipoprotein cover of both HDL and LDL. The HDL enzyme, paraoxinase (PON), helps protect it from oxidation,⁷ so the LDL molecule is more susceptible to oxidation than HDL. This oxidation can occur in areas of the artery where there is physical damage from high blood flow, inflammation or an accumulation of metals including iron or copper, which can be found normally in the body.⁷

Antioxidant protection of LDL helps prevent oxidative changes. It has been known for some time that HDL and LDL carry vitamin E as an antioxidant. However, vitamin E is a fat-soluble vitamin and it has limitations in terms of its ability to prevent oxidation.⁸ Recent information shows that an enzyme called glutathione peroxidase is also carried in both HDL and LDL cholesterol.⁹ This study, done in a laboratory that is well known for research in lipid metabolism and vascular disease, used the dietary supplement liposomal glutathione to demonstrate that supplying a steady supply of the reduced (non-oxidized) form of glutathione is able to prevent the oxidation of LDL cholesterol.⁹

Oxidation’s Devastating Effects

The role of oxidation stress has been debated in regard to the formation of atherosclerosis.¹⁰ Artery blockage by fatty plaques was initially thought to be due to a simple overload of cholesterol. It turns out that the turnover of cholesterol and the ability to remove damaged or oxidized cholesterol plays a critical role in avoiding the collection of lipids in arteries and the formation of plaque. The scavenger cells called macrophages play a critical role in converting the “waste” or oxidized low density lipoprotein (oxLDL) containing cholesterol into a form that can be handed off to HDL and transported back to the liver.¹¹

Oxidized LDL cholesterol needs some special handling by the scavenger cells used to “clean up” the lining of arteries called macrophages. Even in the macrophage cells, an excess of oxLDL can become toxic.^12-15 While most cells can regulate the amount of LDL they ingest, the macrophages and the smooth muscle cells lining arteries cannot limit the amount of oxLDL they take in. The unlimited ingestion of oxLDL results in a large collection of cholesterol inside both macrophages and smooth muscle cells to the point that they look foamy under the microscope. These cholesterol laden cells then become toxic, pile up and create the foundation for the formation of plaque. The toxicity of oxLDL can lead to damage to the endothelial lining and will cause the adhesion of platelets and the local release of growth factors¹⁶ and inflammatory factors that are associated with artery narrowing or clots.¹⁷

Oxidized LDL can be measured in blood and increased levels of oxLDL correlate with the progression of coronary artery disease.¹⁸ The role of oxLDL in promoting atherosclerosis is demonstrated in a study of mice that have a gene defect leading to high levels of LDL and atherosclerosis. In these mice, if the oxLDL was removed by increasing the liver absorption of oxLDL they did not develop as much atherosclerosis even though the LDL level was very high.¹⁹

Elevated levels of oxLDL are also found in other metabolic conditions related to vascular disease including stroke.²⁰ Abnormalities related to oxidized LDL are found in the early stages of metabolic diseases that are associated with atherosclerosis such as metabolic syndrome,²¹ diabetes and obesity.²²

The importance of oxLDL is illustrated by the increased number of research papers identified by the library of medicine search engine PubMed in regard to the phrase “oxidized LDL.” In 1989, there were only 25 papers corresponding to oxidized LDL. In 1999 the number was 324. The number has now (early 2010) grown to over 5,600.

Conclusion

OxLDL is now recognized as both a biomarker and also a cause of atherosclerosis.²³ The study with liposomal glutathione, which shows that a steady supply of glutathione can help delay the oxidation of LDL and slow the development of atherosclerotic plaque in the mouse model of atherosclerosis, should encourage more research.⁹ Monitoring the levels of oxLDL through a newly offered test that is now available here may also provide an early indicator of the early changes in the metabolism related to metabolic syndrome, diabetes and progression of atherosclerosis.

It is now understood that the progression of atherosclerosis is multifaceted; there are many players involved including oxLDL, fibrinogen, homocysteine, C-reactive protein and other lipid constituents that can now be tested for beyond even these factors. Remaining expansive on one’s thinking about cardiovascular disease will be essential as knowledge continues to grow rapidly.

References

1. Alberts B BD, Lewis J, et al., editor. Molecular Biology of the Cell. 3rd ed. New York, N.Y: Garland Publishing; 1994.
2. Mehta JL. Oxidized or Native Low-Density Lipoprotein Cholesterol: Which Is More Important in Atherogenesis? Journal of the American College of Cardiology. 2006;48(5):980-2.
3. Ferretti G, Bacchetti T, Masciangelo S, Bicchiega V. HDL-paraoxonase and Membrane Lipid Peroxidation: A Comparison Between Healthy and Obese Subjects. Obesity (Silver Spring) Md. 2009. Cited in PubMed; 19834469.
4. Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, et al. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. The Journal of Clinical Investigation. 1989;84(4):1086-95.
5. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. The Journal of Clinical Investigation. 1991;88(6):1785-92.
6. Ross R. Atherosclerosis - An Inflammatory Disease. N Engl J Med. 1999;340(2):115-26.
7. Mertens A, Holvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. Faseb J. 2001;15(12):2073-84.
8. Dotan Y, Lichtenberg D, Pinchuk I. No evidence supports vitamin E indiscriminate supplementation. BioFactors (Oxford, England). 2009;35(6):469-73.
9. Rosenblat M, Volkova N, Coleman R, Aviram M. Anti-oxidant and anti-atherogenic properties of liposomal glutathione: studies in vitro, and in the atherosclerotic apolipoprotein E-deficient mice. Atherosclerosis. 2007;195(2):e61-8.
10. Stocker R, Keaney JF, Jr. Role of Oxidative Modifications in Atherosclerosis. Physiol Rev. 2004;84(4):1381-478.
11. Rader DJ, Pure E. Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell? Cell metabolism. 2005;1(4):223-30.
12. Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis (Dallas, Tex. 1983;3(3):215-22.
13. Colles SM, Irwin KC, Chisolm GM. Roles of multiple oxidized LDL lipids in cellular injury: dominance of 7 beta-hydroperoxycholesterol. Journal of lipid research. 1996;37(9):2018-28.
14. Colles SM, Maxson JM, Carlson SG, Chisolm GM. Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends in cardiovascular medicine. 2001;11(3-4):131-8.
15. Chisolm GM, 3rd, Morel DW. Lipoprotein oxidation and cytotoxicity: effect of probucol on streptozotocin-treated rats. The American journal of cardiology. 1988;62(3):20B-6B.
16. Escargueil-Blanc I, Salvayre R, Vacaresse N, Jurgens G, Darblade B, Arnal J-F, et al. Mildly Oxidized LDL Induces Activation of Platelet-Derived Growth Factor {beta}-Receptor Pathway. Circulation. 2001;104(15):1814-21.
17. Liao L, Starzyk RM, Granger DN. Molecular Determinants of Oxidized Low-Density Lipoprotein-Induced Leukocyte Adhesion and Microvascular Dysfunction. Arteriosclerosis, thrombosis, and vascular biology. 1997;17(3):437-44.
18. Johnston N, Jernberg T, Lagerqvist B, Siegbahn A, Wallentin L. Improved identification of patients with coronary artery disease by the use of new lipid and lipoprotein biomarkers. The American journal of cardiology. 2006;97(5):640-5.
19. Ishigaki Y, Katagiri H, Gao J, Yamada T, Imai J, Uno K, et al. Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis. Circulation. 2008;118(1):75-83.
20. Uno M, Harada M, Takimoto O, Kitazato KT, Suzue A, Yoneda K, et al. Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement. Neurol Res. 2005;27(1):94-102.
21. Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR, Jr. Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. Jama. 2008;299(19):2287-93.
22. Njajou OT, Kanaya AM, Holvoet P, Connelly S, Strotmeyer ES, Harris TB, et al. Association between oxidized LDL, obesity and type 2 diabetes in a population-based cohort, the Health, Aging and Body Composition Study. Diabetes/metabolism research and reviews. 2009.
23. Ishigaki Y, Oka Y, Katagiri H. Circulating oxidized LDL: a biomarker and a pathogenic factor. Current opinion in lipidology. 2009;20(5):363-9.

Perhaps no other health topic deserves more attention than that of adrenal function due to the fact that adrenal burnout is one of the primary causes of the low energy and fatigue that many people suffer from today. Furthermore, these two walnut-sized glands secrete hormones that affect every major physiological process in the body.

The primary function of the adrenal glands is to manage perceived stress. However, ironically, the adrenal mechanisms designed to protect us from danger can be dangerous to our health and well-being. This is because chronic stress has multiple, deleterious consequences.

This article will focus on “adrenal fatigue” and strategies for helping the ever-growing population who is experiencing it.¹

Modern Stress and the Human Body

Adrenal fatigue, whether mild to severe, is usually secondary to some form of stress. Modern chronic stress can take the form of mental/emotional (relationships, job, money), environmental pollution, chronic infection or illness, noise, traffic, crowds, terrorism, data overload, decisions, deadlines, delays, electromagnetic fields (EMFs), social pressures, over/under exercise, alcohol, cigarettes, medications, caffeine, excess sugar/refined carbohydrates, insomnia, skipping meals, harmful food quality, allergens, etc. And it’s not just the type of stressors, but the pile-up effect of multiple stressors.

Stress is defined as any disturbance that can trigger the “stress response,” generally recognized to occur through a series of three stages called the General Adaptation Syndrome.

I. The first stage, alarm, is the body’s initial response to stress, which activates the sympathetic nervous system. This causes the release of the adrenal catecholamines, adrenaline and nor-adrenaline, which are released into the bloodstream increasing heart rate, blood pressure, and alertness, physically preparing the body for a fight or flight. In addition, the brain sends hormone messengers (CRH, ACTH) to the adrenals through the HPA (hypothalamic-pituitary-adrenal) axis. An activated HPA axis results in the release of stress hormones, in particular cortisol, along with other mediators such as growth factors and cytokines. This is an immediate short-term response to stress and when abated, the HPA axis is turned off in a negative feedback loop while the parasympathetic system balances and relaxes the nervous system.

Figure 1. Pathways of Steroid Hormone Synthesis from the Brain to the Adrenal Glands (Simplified)

II. The second stage, resistance, occurs if the stress is prolonged. Many steroid hormones are made in the adrenal glands through the conversion of cholesterol to pregnenolone (fig 1). In this stage, the adrenals begin preferentially shunting pregnenolone into increased production of the main stress hormone cortisol and to a lesser extent, aldosterone. These hormones ensure that blood pressure does not drop (sodium retention) and that protein is converted to glucose to supply energy long after glucose stores are depleted. Cortisol reigns in this stage and is responsible for many of the life-sustaining properties of the adrenal glands. Some people remain in this stage with elevated cortisol much of their lives. Although proper cortisol levels are beneficial, high levels, over time, result in physiological changes and diseases attributed to chronic stress. Equally affected by high cortisol, the negative feedback loop of the HPA axis becomes disrupted as the hypothalamus gland becomes less sensitive to the signal that tells it to stop producing the messenger hormone.² HPA axis overdrive results in what is called maladaptation. Unfortunately, with enough high-intensity stressors for a long enough period, most people will maladapt.

III. Unremitting stress, maladaptation and loss of adrenal gland reserve lead to a decreased production of stress hormones such as cortisol, aldosterone, epinephrine and DHEA. Many individuals visit or reside in this third and final stage of adaptation to stress called the exhaustion stage. Here the glands are failing to optimally meet the demands placed upon them and fatigue intensifies. Adrenal hormone deficiency, especially cortisol, causes a loss of glucose to the cells for energy. This alone is a major reason for fatigue. The exhaustion stage may develop gradually or be precipitated by a single serious event such as an illness, infection, injury or crisis. Regardless of the onset, it is associated with many disorders.³ Adrenal deficiency, called adrenal hypofunction or hypoadrenalism by many doctors, can range in severity. Adrenal fatigue should not be confused with Addison’s disease, which is the adrenal failure state. Adrenal fatigue is largely caused by stress while Addison’s disease is an autoimmune condition in about 80 percent of cases.⁴

Symptoms of Adrenal Fatigue.

The adrenals respond the same to every kind of stress no matter the source, yet people are genetically different in their response to stress making them more or less vulnerable to stress-related disorders.⁵ With prolonged stress, chronic fatigue presents as the major complaint, but stress also can contribute to depression, anxiety, weight gain and have diverse effects on the gastrointestinal tract and other organs.

An individual with adrenal fatigue is typically described as someone who wakes up tired, depends on caffeine to “get through the day,” craves sweets, feels light-headed or irritable before a meal, may get a “second wind” in the evening, and has trouble with sleep. They often have a history of skipping meals and/or a diet high in refined carbohydrates, synthetic additives and trans-fats, all of which helped contribute to the adrenal fatigue. They commonly resonate with “all work and no play.” Some have suffered a major crisis, have a chronic infection, or are repeatedly exposed to toxins as environmental, drugs, alcohol or food sensitivities. The signs and symptoms for adrenal fatigue commonly include those listed in Table 1.

Many factors must be considered when evaluating an individual with adrenal fatigue. Mainstream medicine and many research studies focus on identifying an infectious agent as the cause. The Epstein-Barr Virus (EBV) emerged as the leading, yet controversial, candidate^6-9 thought to be linked to chronic fatigue syndrome (CFS). The connection to adrenal fatigue is that chronic infections caused by infectious organisms such as viruses, bacteria or fungi, nearly always lead to adrenal fatigue.

Stress and the Adrenals

The adrenal hormones, cortisol in particular, have many regulatory functions influencing all major systems and the utilization of carbohydrates, proteins, fats and minerals. For example, one of cortisol’s main functions is to make glucose (blood sugar) available from body stores between meals or when a stressful event demands it. Insufficient cortisol results in suboptimal glucose levels or hypoglycemia¹⁰ causing symptoms of fatigue, light-headedness, shakiness or irritability if meals are delayed or missed.¹¹ Less available glucose leads to cravings for fast-acting carbohydrates (sweets, breads, alcohol) creating insulin fluctuations and diabetes risk. The demand for nutrient cofactor support from vitamin C, minerals and B vitamins is increased. Insufficiencies of these and other nutrients contribute to the symptoms of a person with adrenal fatigue. Blood glucose levels are also maintained during sleep through the breakdown of glycogen under the influence of cortisol. In most cases, the inability to stay asleep during the night is a blood sugar issue. A drop in fasting glucose during sleep, due to a lack of cortisol, sparks a stress response activating the catecholamines to raise glucose levels to compensate. Since catecholamines are stimulatory they cause awakening, thereby adding to the fatigue problem.

The HPA axis and cortisol help prevent an over-zealous immune system activation of inflammation. When cortisol is decreased, individuals become more susceptible to inflammatory responses.¹² This may be seen as slow tissue healing, autoimmune disorders, joint and muscle pain and hypersensitivity reactions (allergies, hay fever, asthma, eczema, or hives).

In adrenal fatigue, there may be decreased catecholamines secretion, affecting vascular tone, associated with lowered blood pressure. A common feature of serious adrenal fatigue, “orthostatic hypotension” is often marked by a dizzy feeling when arising from a lying or sitting position to standing (orthostatic).

Additionally, the low levels of aldosterone that occur during adrenal fatigue result in the tendency to retain potassium and lose sodium, chloride and water. Any loss of sodium-rich extracellular fluid creates a state of dehydration, resulting in the craving for salt and water that are necessary for adrenal recovery.

Finally, healthy thyroid function depends upon proper adrenal function. Hypothyroidism (low thyroid function) is often secondary to adrenal stress.¹³ Furthermore, some low thyroid symptoms, such as depression and hair loss, are similar to those of adrenal fatigue. For example, one of the reasons why adrenal stress affects thyroid function is because the thyroid depends on the same hypothalamus/pituitary communication system as the adrenals; therefore, with maladaptation, the communication with the thyroid gland is also disrupted.^14-15

Figure 2. The Normal Circadian Rhythm of Cortisol (with and without snacks)

Cortisol (and other adrenal hormones) normally follow a diurnal pattern of secretion. After its peak around 8 a.m., it downtrends through the day with small spikes. With adrenal fatigue, eating and snacking helps to support higher cortisol. (Adrenal fatigue patterns usually show lower AM cortisol and possibly different patterns throughout the day.) Adapted from Wilson JL. Adrenal Fatigue, The 21st Century Stress Syndrome. Petaluma, Ca. Smart Publications, 2001 pg 266.

Diagnosing Adrenal Fatigue

The first step in determining if someone is suffering from adrenal fatigue is to measure cortisol levels. This is done through a salivary adrenal function test, which measures the daily variations in cortisol concentration. The normal circadian rhythm of cortisol is characterized by a steep increase in the morning (8 a.m. peak), followed by a gradual tapering off until about midnight where the levels are lowest (fig 2). The loss of morning cortisol was seen in studies of chronic fatigue syndrome (CFS).¹⁶ If the results of one’s salivary adrenal function panel show low morning cortisol, it points directly to HPA axis dysfunction and adrenal fatigue (or exhaustion).¹⁷ The test will also indicate levels of DHEA, a hormone important in adrenal health. The test is helpful in choosing the best course of action for optimizing adrenal function.

Or, individuals can choose to take a salivary Comprehensive Hormone Panel, which can also help determine progesterone and DHEA levels in addition to cortisol levels throughout the day. Maintenance of sufficient levels of progesterone, a direct precursor to cortisol, is important for all but particularly for stressed postmenopausal women who have lost the ovarian production of hormones and depend on the adrenal gland to supply them.

Lifestyle Changes

In people whose test results show low cortisol levels, the adrenal situation must be normalized. This can be accomplished in part through at least 8 hours of sleep (bed by 10 p.m.) and identifying and removing stressors.

One of the most significant stressors to remove is the exposure to high-glycemic-load diets of refined sugars and carbohydrates that create insulin fluctuations and shift the HPA axis toward sympathetic over-activity.^18-19 A low-glycemic diet balanced in protein, healthy fats, and complex carbohydrates like vegetables, eaten as smaller meals more frequently (5-6 small meals/day), has a positive influence on hormone signaling^20-21 (see fig 2). Protein is important for the adrenals and requires adequate stomach acid (HCL) for digestion. Individuals with adrenal fatigue are notoriously low in HCL, and HCL supplementation (GastricAid^®) is therefore recommended for adrenal fatigue.

Other adrenal stressors to avoid are caffeine, stimulating drugs, alcohol, allergenic foods, artificial sweeteners (aspartame), nicotine and partially hydrogenated oils. Exercise is encouraged, such as walking, gradually increasing distance and pace.

It is important to note that the adrenals need cholesterol to make adrenal hormones. Avoiding fats (both saturated and unsaturated) and excessively lowering cholesterol levels, as with statin drugs, deprives the adrenals of adrenal hormone precursors, increasing the risk for such conditions as depression and impulsive behavior.²² Also, if an individual persists with anemia, infections, leaky gut or food allergies, over-exercise, low cholesterol (below 150), unstable blood sugar or severe emotional stress, it may be more difficult to achieve a positive change in the salivary adrenal test.

Natural Adrenal Support

Addressing adrenal gland depletion while concomitantly supporting HPA axis receptor sensitivity is the goal of an adrenal-supporting supplement regimen. This regimen can result in improved adrenal function and increased energy. Vitamin C with bioflavonoids and vitamins B5 and B6 are important adrenal nutrients along with B1 and zinc, which are particularly important for needed blood sugar balance. Zinc is also necessary for the ACTH response. L-carnitine supports the burning of fats (fatty acids) for energy, which contributes to better glycemic control between meals and proper weight management. Another amino acid, L-tyrosine enhances dopamine and catecholamine synthesis and improves stress-associated declines in noradrenaline and performance.²³

Adaptogens include botanicals containing compounds that support the stress response through producing a normalizing effect on the HPA axis. They are capable of a bi-directional effect, supporting the gland in times of over-secretion or under-secretion of stress hormones. One such adaptogen is Eleutherococcus senticosis, found to have even greater anti-fatigue properties than Panax ginseng, and to improve work output, presumably through better oxygen uptake and metabolism. It has decreased fatigue severity and duration and optimized HPA axis function under stress.^24-28 Another adaptogen is Rhodiola rosea, which has roughly 200 scientific studies since 1960 to support its effective long-term use in combating fatigue, restoring energy, improving memory and mental performance with less mental fatigue, and enhancing proper thyroid activity.^28-33 Bacopa monnieri also plays an adaptogenic role. It has many impressive cognitive and anti-fatigue benefits and positively influences the retention of new information learned. Studies also show significant antidepressant effects.^34-40

Licorice root extract works with the above adaptogens. Its components glycyrrhizin and glycyrrhetinic acid impact enzymes that result in a net increase of cortisol availability, which is restorative for the adrenal glands.^41-42

Another successful way to support recovery from stress is through the use of adrenal glandulars, the cornerstone of potent, effective adrenal therapy. The glandulars provide essential constituents of nucleic acids and other cellular factors without the damaging side effects of synthetic cortisol.^43-44

Each of the natural adrenal-supporting substances mentioned above are found in VRP’s newly reformulated CortiTrophin^®, intended to support the stress response on multiple fronts.

Additional support can be given to the adrenals by supplementing with Extension B-Plex (B complex), HCL as GastricAid^®, as well as DHEA and Gentle Changes^® progesterone cream if the Comprehensive Hormone Panel indicated these two hormones are warranted. Testing zinc levels through the ZincMate^™ test is also recommended. Because people with adrenal fatigue are often salt depleted, it’s also important to nourish the adrenals by using a Celtic Sea Salt that contains a blend of natural minerals.

Conclusion

The aforementioned botanicals, vitamins, amino acids and adrenal glandular found in the new and improved CortiTrophin offer an effective and comprehensive approach toward improved adrenal health, especially when combined with diet, lifestyle, rest and stress management. After undertaking this regimen, individuals whose salivary hormone test indicates low cortisol levels will likely experience enhanced energy and an improved quality of life.

For best results, use CortiTrophin for 6 to 8 weeks, then discontinue for one week before resuming use again, following this schedule as needed.

References

1. Tintera JW. The hypoadrenocortical state and its management. NY State J Med. 1955;55:1869-1876.
2. Rubello D, Sonino N, Casara D, et al. Acute and chronic effects of high glucocorticoid levels on hypothalamic-pituitary-thyroid axis in man. J Endocrinol Invest. 1992 June;15(6):437-441.
3. Heim C, Ehlert U, Hellhammer DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Chroneuroendocrinology. 2000 Jan;25(1):1-35.
4. Guyton A, Hall J. Textbook of Medical Physiology. 11th ed, Philadelphia: Elsevier Saunders, 2006. pg 957
5. Wust S, et al. Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab. 2004 Feb;89(2):565-573.
6. Kyle DV, deShazo RD. Chronic fatigue syndrome. A conundrum. Am J Med Sci 1992;303:28-34.
7. Straus SE, Tosato G, Armstrong G, et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985;102:7-16
8. Komaroff AL. Chronic fatigue syndromes: relationships to chronic viral infections. J Virol Meth 1988;21:3-10.
9. Demitrack MA. Chronic fatigue syndrome: a disease of the hypothalamic-pituitary-adrenal axis? Ann Med. 1994;26:1-3.
10. Pizzorno J, Murray, M. eds. Textbook of Natural Medicine. 3rd ed, St. Louis: Churchill Livingston, 2006, pg 702.
11. Chalew SA, Koetter H, Hoffman S, et al. Diagnosis of reactive hypoglycemia. Pitfalls in the use of the oral glucose tolerance test. South Med J 1986;79:285-287.
12. Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984 5;25-44.
13. Abdullatif HD, Ashraf AP. Reversible subclinical hypothyroidism in the presence of adrenal insufficiency. Endocr Pract 2006 Sept-Oct;12(5):572
14. Sapolsky RM, Krey LC, Mc Ewens BS. The Neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev. 1986 Aug;7(3):284-301.
15. Cutolo M, Straub R. Stress as a risk factor in the pathogenesis of rheumatoid arthritis. Neuroimmunomodulation 2006;13(5-6):277-282.
16. Roberts AD, et al. Salivary cortisol response to awakening in chronic fatigue syndrome. Br J Psychiatry. 2004 Feb;184:136-41.
17. Guechot J, Fiet J, Passa P, et al. Physiological and pathological variations in saliva cortisol. Hom Res. 1982;16(6):357-364.
18. Tentolouris N, Tsigos C, Perea D, et al. Differential effects of high-fat and high- carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women. Metabolism. 2003;52(11):1426-32.
19. Vicennati V, Ceroni L, Gagliardi L. et al. Comment: response of the hypothalamic-pituitary-adrenocortical axis to high-protein/fat and high-carbohydrate meals in women with different obesity phenotypes. J Clin Endocrinol Metab. 2002;87(8):3984-88.
20. Pereira MA, Swain J,Goldfine AB, et al. Effects of a low-glycemic-load diet on resting energy expenditure and heart disease risk factors during weight loss. JAMA. 2004;292(20):2482-90.
21. Farshchi HR, Taylor MA, Macdonald IA. Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women. Am J Clin Nutr. 2005;81(1):16-24.
22. Ormiston T, Wolkowitz OM, Reus VI, et al. Behavioral implications of lowering cholesterol levels: a double-blind pilot study. Psychosomatics. 2003;44(5):412-414.
23. Zabriskie Nieske. The physical manifestations of emotional stress. Vitamin Research News. Available online at www.vrp.com.
24. Kimura Y, Sumiyoshi M. Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice. J Ethnopharmacol 2004 Dec;95(2-3):447-53.
25. Farnsworth NR, Kingdorn AD, Soejarto D, Waller DP. Siberian ginseng (Eleutherococcus senticosus): Current status as an adaptogen. Econ Med Plant Res. 1985;1:156-215.
26. Fulder SJ. Ginseng and the hypothalamic-pituitary control of stress. Am J Chin Med. 1981;9(2):112-18.
27. Hartz AJ, Bentler S, Noyes R, Hoehns J, Logemann C, Sinift S, Butani Y, Wang W, Brake K, Ernst M, Kautzman H. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med 2004 Jan;34(1):51-61.
28. Brekhman II, Dardymov IV. New substances of plant origin which increase non-specific resistance. Ann Rev Pharmacol 1969;9:419-30.
29. Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev 2001;6:293-302.
30. Shevtsov VA, Zholus BI, Shervarly VI, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine 2003;10:95-105.
31. Mattioli L, Perfumi M. Evaluation of Rhodiola rosea L. extract on affective and physical signs of nicotine withdrawal in mice. J Psychopharmacol. 2009 Nov 25. Published Online Ahead of Print.
32. Olsson EM, von Schéele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. 2009 Feb;75(2):105-12.
33. Brown R, et al. Rhodiola rosea: a phytomedicinal overview. HerbalGram 2002;56:40-52.
34. Roodenrys S, Booth D, Bulzomi S, et al. The chronic effects of Brahmi (Bacopa monniera) on human memory. Neuropsychopharmacology. 2002 Aug27;(2):279-81.
35. Sairam K, Dorababu M, et al. Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Phytomedicine. 2002 Apr;9(3):207-11.
36. Jyoti A, Sharma D. Neuroprotective role of Bacopa monniera extract against aluminum-induced oxidative stress in the hippocampus of rat brain. Neurotoxicology. 2006 Jul27;(4):451-57.
37. Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine. 2005 Apr;12(4):305-17.
38. Calabrese C, et al. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008;14(6):707-13.
39. Sheikh N, Ahmad A, et al. Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monamines in rats. J Ethnopharmacol. 2007 May22;111(3):671-76
40. Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl). 2001 Aug;156(4):481-4
41. Tamura Y, Nishikawa T, Yamada K, et al. Effects of glycyrrhetinic acid and its derivatives on delta 4-5 alpha- and beta-reductase in rat liver. Arneimittelforschung. 1979;29(4):647-9.
42. van Uum SH, Walker BR, Hermus AR, et al. Effect of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects. Clin Sci (Colch) 2002;102:203-11.
43. Britton SK, RF.. The relative effects of desoxycorticosterone and the whole cortico-adrenal extract on adrenal insufficiency. The American Journal of Physiology. 1941;133(3)503-10.
44. Wilson JL. Adrenal Fatigue, The 21st century Stress Syndrome. Petaluma: Smart Publications, 2001, pg 209-216.

Inflammation is a protective physiological process in which the immune system is activated in an attempt to fight off pathogens or respond to injuries. The inflammatory process involves the activation of white blood cells, increased permeability of the blood vessels and release of several cell signaling molecules. It generally presents with heat, swelling, pain and redness. However, the inflammatory response can become chronic, in which it is activated regardless of acute infection, irritant or injury. This chronic inflammatory process is the basis for numerous diseases such as allergies, arthritis, asthma, cardiovascular disease, autoimmune diseases and inflammatory bowel disease.

Now, researchers have uncovered another health concern associated with inflammation: Cognitive impairment.

Cognitive impairment is one term used to describe any of a group of cognitive disorders including mild cognitive impairment, age-related cognitive decline, vascular dementia, decreased long-term memory formation and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.

Although the exact mechanism as to why inflammation may impair memory is unclear, one theory suggests that inflammation disrupts the integrity of the blood-brain barrier, which is a highly selective membrane that protects the brain from pathogens in the blood, as well as regulates which molecules can pass between the blood and cerebral spinal fluid. Inflammation decreases the barrier function of the membrane, which allows large molecules, such as plasma proteins, access to the brain resulting in neuronal damage.¹ Another theory suggests that inflammation promotes neurodegeneration by activating microglial cells, which are primary immune cells in the central nervous system. Activated microglial cells secrete a variety of pro-inflammatory cytokines (chemical mediators), including interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor (TNF), as well as reactive oxygen and nitrogen species that cause free radical damage. The reactive oxygen and nitrogen species alter glucose uptake in the neurons and can impair signaling of the neurons. Also, activation of microglial cells has been shown to cause neuronal cell death.²

Understanding Cognitive Concerns

Mild cognitive impairment is the diagnosis for memory deficits beyond what is expected for normal aging but less severe than dementia. It presents with memory loss, slower thinking, and a decreased ability to learn, but does not interfere with the activities of daily living. It is estimated that age-related cognitive decline affects nearly one-third of adults.³ Individuals with mild cognitive impairment may progress to dementia, and possibly to Alzheimer’s disease. Dementia affects approximately 14 percent of adults age 71 and older,⁴ and 5.3 million Americans age 65 and older, about one in eight, have Alzheimer’s disease.⁵ Alzheimer’s disease is the most common type of dementia, accounting for nearly 40 percent of dementia cases, and it is estimated that by mid-century, someone will develop Alzheimer’s every 33 seconds in the United States. Furthermore, Alzheimer’s disease is the seventh leading cause of death in the United States.⁶

Alzheimer’s disease is a progressive condition characterized by memory loss, confusion, irritability and aggression, and gradual loss of ability to perform normal daily activities. In Alzheimer’s disease, there is a deposition of beta-amyloid protein between nerve cells and accumulation of tau proteins, known as neurofibrillary tangles, within the nerve cells. There is also evidence that inflammation and oxidative stress plays a role in the development and progression of this disease. Vascular dementia is the second most common form of dementia after Alzheimer’s disease, and is associated with strokes or transient ischemic attacks (TIAs). Parkinson’s disease is the second most prevalent age-related neurodegenerative disorder after Alzheimer’s disease. Parkinson’s disease is characterized by a slow and progressive degeneration of dopaminergic neurons (nerve cells that primarily secrete the neurotransmitter dopamine) in the area of the brain known as the substantia nigra. It is characterized by tremors, slowed physical movements, abnormal postural reflexes, rigidity and the inability to initiate movement.

Inflammation as a Cognitive Killer

Research indicates that chronic inflammation plays a role in the development of cognitive impairment. In one study, investigators evaluated subjects between the ages of 70 and 89 for levels of cognitive ability and were categorized as having normal cognition, mild cognitive impairment or dementia. The subjects were also evaluated for pro-inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis alpha (TNF-alpha). CRP is a non-specific inflammatory marker that is increased in the brain and serum of patients with Alzheimer’s disease, and is associated with an increased risk of developing dementia. The results of the study showed a significant association between elevated CRP levels and increased risk of mild cognitive impairment. In fact, the subjects with the highest levels of CRP had more than double the risk of developing mild cognitive impairment compared to the subjects with low CRP levels.⁷ In another study, researchers evaluated inflammatory markers including fibrinogen and CRP levels in subjects with dementia. The results showed that dementia patients had significantly higher CRP levels compared to healthy control subjects. Additionally, the study found that the subjects with Alzheimer’s disease had higher CRP levels than the subjects diagnosed with vascular dementia.⁸

Another interesting study evaluated the impact of acute inflammation on the progression of cognitive decline in subjects with Alzheimer’s disease. The subjects were cognitively assessed and evaluated for levels of TNF-alpha, a pro-inflammatory cytokine, at the beginning of the study, and after 2, 4, and 6 months. The study found that acute systemic inflammatory events were associated with an increased serum level of TNF-alpha and a 2-fold increase in the rate of cognitive decline over the 6 months. Subjects with a high TNF-alpha level at the beginning of the study showed a 4-fold increase in the rate of cognitive decline. Furthermore, the subjects with normal TNF-alpha levels throughout the 6-month study demonstrated no cognitive decline during the study.⁹

Research also indicates that elevated CRP is associated with double the risk of developing Parkinson’s disease.¹⁰ Studies indicate that inflammation caused by activated glial cells and peripheral immune cells induce oxidative stress and cytokine-receptor-mediated apoptosis (programmed cell death), which could lead to dopaminergic cell death and disease progression.¹¹ Additionally, the release of pro-inflammatory cytokines from microglial cells modulates the blood brain barrier in patients with Parkinson’s disease. This leads to recruitment of passing immune cells, which, in turn, causes the release of more cytokines. Inflammatory cytokines such as IL-8, IFN-gamma, IL-1beta and TNF-alpha have been shown to be significantly higher in patients with Parkinson’s disease compared to healthy control subjects. Furthermore, levels of pro-inflammatory cytokines were proportional to the stage of the disease, showing increased cytokine levels with increased disease severity.¹²

Natural Approach to Inflammation Control

Numerous botanicals have been shown to provide anti-inflammatory and antioxidant activity, which may protect the brain from inflammatory damage. Herbs such as Stephania tetrandra, Urtica dioica (stinging nettle), Ocimum sanctum (holy basil), Zingiber officinale (ginger), Boswellia serrata (frankincense), Camellia sinensis (green tea), and Perilla frutescens (as found in Advanced Inflammation Control) have been shown to decrease various inflammatory mediators associated with cognitive impairment.

Several studies have shown that ginger inhibits pro-inflammatory cytokines, including IL-1beta, IL-2, IL-12, TNF-alpha, and interferon (IFN)-gamma.¹³ Ginger also has been shown to decrease synthesis of pro-inflammatory prostaglandins and leukotrienes by inhibition of cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) enzymes, which are the targets for numerous anti-inflammatory pharmaceuticals. Similarly, holy basil leaf inhibits both COX and 5-LOX,¹⁴ and the boswellic acids derived from Boswellia known as AKBA are potent inhibitors of the 5-LOX enzyme.¹⁵

The anti-inflammatory constituents tetrandrine and fangchinoline found in Stephania tetrandra have been shown to decrease IL-1beta, IL-6, IL-8 and TNF-alpha,¹⁶ as well as decrease leukotriene and prostaglandin generation.¹⁷ More importantly, tetrandrine has been shown to inhibit the production TNF-alpha and IL-6 production by microglial cells,¹⁸ which have been shown to damage nerve cells. In addition, the green tea polyphenol EGCG has been shown to inhibit the production of numerous inflammatory mediators, including TNF-alpha, IL-1 beta and IL-6.¹⁹ Furthermore, green tea has been shown to cross the blood brain barrier, reduce inflammation, provide antioxidant activity, and reduce neural cell death.²⁰ Luteolin, a flavonoid found in high concentrations in the herb Perilla frutescens, has also been shown to inhibit pro-inflammatory cytokines associated with neuron damage, including TNF-alpha, IL-6, and IL-8.^21-22 Similarly, Urtica dioica reduces IL-1 beta, IL-2, IFN-gamma, and TNF-alpha.^23-24 Supplementation of stinging nettle in humans has been shown to decrease lipopolysaccharide induction of inflammatory mediators, triggering an 80 percent reduction in TNF-alpha and a 99 percent reduction in IL-1 beta. ²⁵

Conclusion

Low levels of persistent inflammation affect all body systems, including the nervous system. In the brain, chronic inflammation can result in cognitive dysfunction, as well neuronal cell death. Numerous botanicals have been shown to decrease the inflammatory mediators causing the symptoms related to cognitive dysfunction. Additionally, botanicals such as green tea have directly reduced inflammatory-related cell death in the brain.

References

1. Stolp HB, Dziegielewska KM. Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathol Appl Neurobiol. 2009 Apr;35(2):132-46.
2. Hansen E, Krautwald M, Maczurek AE, et al. A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds. J Alzheimers Dis. 2010;19(2):451-64.
3. Low LF, Brodaty H, Edwards R, et al. The prevalence of “cognitive impairment no dementia” in community-dwelling elderly: a pilot study. Aust N Z J Psychiatry. 2004 Sep;38(9):725-31.
4. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1-2):125-32.
5. Hebert LE, Scherr PA, Bienias JL, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003 Aug;60(8):1119-22.
6. Alzheimer’s Association. 2009 Alzheimer’s Disease Facts and Figures. Available at: http://www.alz.org/national/documents/report_alzfactsfigures2009.pdf. Accessed on: 02-07-10.
7. Roberts RO, Geda YE, Knopman DS, et al. Association of C-reactive protein with mild cognitive impairment. Alzheimers Dement. 2009 Sep;5(5):398-405.
8. Mancinella A, Mancinella M, Carpinteri G, et al. Is there a relationship between high C-reactive protein (CRP) levels and dementia? Arch Gerontol Geriatr. 2009;49 Suppl 1:185-94.
9. Holmes C, Cunningham C, Zotova E, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology. 2009 Sep 8;73(10):768-74.
10. Song IU, Kim JS, Chung SW, et al. Is there an association between the level of high-sensitivity C-reactive protein and idiopathic Parkinson’s disease? A comparison of Parkinson’s disease patients, disease controls and healthy individuals. Eur Neurol. 2009;62(2):99-104.
11. Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009 Apr;8(4):382-97.
12. Reale M, Iarlori C, Thomas A, et al. Peripheral cytokines profile in Parkinson’s disease. Brain Behav Immun. 2009 Jan;23(1):55-63.
13. Tripathi S, Bruch D, Kittur DS. Ginger extract inhibits LPS induced macrophage activation and function. BMC Complement Altern Med. 2008 Jan 3;8:1.
14. Singh S, Majumdar DK, Rehan HM. Evaluation of anti-inflammatory potential of fixed oil of Ocimum sanctum (Holybasil) and its possible mechanism of action. J Ethnopharmacol. 1996 Oct;54(1):19-26.
15. Uz T, Pesold C, Longone P, et al. Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability. FASEB J. 1998;12:439-49.
16. Tak P, Firestein G. NF-kB: a key role in inflammatory disease. J Clin Invest. 2001;107:7-11.
17. Teh BS, Seow WK, Li SY, et al. Inhibition of prostaglandin and leukotriene generation by the plant alkaloids tetrandrine and berbamine. Int J Immunopharmacol. 1990;12(3):321-6.
18. Xue Y, Wang Y, Feng DC, et al. Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-kappaB pathway. Acta Pharmacol Sin. 2008 Feb;29(2):245-51.
19. Neyestani TR, Gharavi A, Kalayi A. Selective effects of tea extract and its phenolic compounds on human peripheral blood mononuclear cell cytokine secretions. Int J Food Sci Nutr. 2009;60 Suppl 1:79-88.
20. Mandel SA, Avramovich-Tirosh Y, Reznichenko L, et al. Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals. 2005;14(1-2):46-60.
21. Kim JA, Kim DK, Kang OH, et al. Inhibitory effect of luteolin on TNF-alpha-induced IL-8 production in human colon epithelial cells. Int Immunopharmacol. 2005; 5:209-17.
22. Kotanidou A, Xagorari A, Bagli E, et al. Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice. Am J Respir Crit Care Med. 2002;165:818-23.
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24. Konrad A, Mähler M, Arni S, et al. Ameliorative effect of IDS30, a stinging nettle leaf extract, on chronic colitis. Int J Colorectal Dis. 2005;20:9-17.
25. Teucher T, Obertreis B, Ruttkowski T et al. Cytokine secretion in whole blood of healthy subjects following oral administration of Urtica dioica L. plant extract. Arzneimitt. 1996;46:906-10.

There are three different forms of fatty acids. These are omega-3s, which are considered the healthy form, omega-6s, which our pets get large amounts of in their normal diet, and omega-9s, which are contained in olive oil and avocados. Omega-9 fatty acids are monounsaturated and are considered healthy fats as they are a large part of the Mediterranean diet.

We need to understand that, like us, pets need to have some of each of the fatty acids. Essential fatty acids are the omega-3 and omega-6 fatty acids. They are considered essential because the animals are unable to make them from other consumed fatty acids.

The omega-6 fatty acids help with the structure and ability for the vascular system to hold its integrity. Without omega-6s, pets’ blood pressure would drop too low to be compatible with life. With too much omega-6s, the vascular system tends to become too rigid, and, as in people, leads to high blood pressure. This does happen in our pets but not at the same level as it does in Homo sapiens.

Omega-3 fatty acids act as anti-inflammatory nutrients. The metabolic cascade that omega-3 fatty acids pass through will lead to anti-inflammatory products for the body.

However, to achieve an anti-inflammatory response, the dose level of omega-3s should be in the range of 40 to 80 milligrams per kilogram of body weight. At levels in this range, most animals seem to have less pain from osteoarthritis and get around much better.

Omega-3s from flax seed oil, borage oil, etc. primarily contain alpha linolenic acid (ALA), which is not as effective in animals. Cats and dogs have to break the ALA down to eicosapentaeoic (EPA) and docosahexanoic (DHA) acid, which are the active forms of the omega-3 fatty acids, and their metabolism does a poor job at making that conversion.

The anti-inflammatory effects of omega-3s are very good to help control the pain of arthritis, different forms of dermatitis, dry skin and brittle hair, decreasing the symptoms of allergies and atopy (hypersensitivity or allergic reaction), and they may increase survival rates is several types of cancer along with increased survival time in combination with chemotherapy.

Krill Oil Plus is a very pure source of omega-3 fatty acids. There are 1.3 grams or 1,300 mg in two capsules, of which, 450 mg is in the form of omega-3 fatty acids. That is a good dose for a 10 to 20 pound dog and can be given once daily. It takes six to twelve weeks for the omega-3s to be incorporated into the cell membranes. If you happen to miss a dose, just continue on the same dose the next day as opposed to doubling up to make up the miss.

Chronic disease wreaks havoc on the American populace. One million Americans suffer from AIDS; eight million have cancer, and twelve million battle heart disease. However, there is one group of disorders that afflicts more individuals than the combined total of all of these other potentially deadly disorders, and, surprisingly, it receives considerably less attention. Thirty-eight million Americans are victims of digestive disorders, including Crohn’s disease, ulcerative colitis, diverticulitis, celiac disease, IBS, constipation, diarrhea, GERD, candida and food allergies.

If these staggering numbers of digestive disorders, along with the pain and discomfort that accompany them, were not enough, there is also the added burden of treatment costs. The economic impact of digestive disorders is $123 billion per year, compared to $17 billion for cancer, $58 billion for neurological disorders, and $88 billion for circulatory problems. Sufferers from IBS (the most common gastrointestinal disorder) incur an estimated $10 billion more in direct medical charges per year than a similar control group of people the same age and gender.1

Digestive Tract Mechanics

Digestion begins in the mouth. Chewing is an important first step in the digestive process, especially for fruits and vegetables, as it breaks down membranes of cellulose (indigestible for humans) and liberates the nutrients they surround. Chewing also breaks food into small pieces, creating a large amount of surface area—digestive enzymes can only work on the surface of food. When food is wolfed down, it takes much longer to digest.

After food is swallowed, it passes through the esophagus into the stomach where digestive enzymes transform the food into a relatively smooth and thick fluid mixture called chyme.

The mucous membrane of the stomach is densely packed with glands that secrete hydrochloric acid and pepsin, a protein-digesting enzyme. The role of hydrochloric acid is to create a sufficiently acid environment for pepsin to be activated. If we do not produce enough hydrochloric acid, then we cannot fully digest protein. The parietal cells that create hydrochloric acid also produce a large protein called the intrinsic factor, necessary for the assimilation of vitamin B12.

The pumping action of the stomach moves the partially digested food along into the duodenum, the first section of the small intestine. It is in the first two sections of the small intestine that most digestion and assimilation occur. Absorption takes place via the villi, small projections in the mucous membrane. Each villus has a network of capillaries through which the broken-down components of the food are absorbed. The nutrients then pass through the epithelial cells in the inner lining of the villi, at which point they enter the capillaries.

Once again, muscular contractions move the digested food along through the ileocecal valve into the large intestine and ultimately, in the final stage of this incredible journey, out of the body.

A Living Environment

The digestive system is far more than a collection of pipes, wiring and membranes. It is actually an ecosystem, populated by billions of organisms that produce substances necessary for digestion to occur—enzymes, vitamins and beneficial bacteria. In the young, gut bacteria interact with intestinal cells, called paneth cells, to promote the development of blood vessels in the intestinal lining. In the large intestine, fermentation processes produce butyric acid and other short-chain fatty acids that nourish the intestinal wall.2

Like all ecosystems, the delicate balance of the digestive tract can be altered by various toxins including antibiotics and other drugs, chemicals like chlorine and fluoride in our water, food additives and preservatives, stimulants like coffee, and an overabundance of difficult-to-digest foods like improperly prepared whole grains.

When the intestinal ecosystem is healthy, beneficial bacteria keep yeasts and other fermentation microorganisms at bay in this part of the digestive tract. An imbalance of microorganisms, called dysbiosis, results in overgrowth of fungus and other pathogens, resulting in numerous digestive disorders.

Other lifestyle factors that lower immunity such as stress and sleep deprivation can also play a role in letting the bad bacteria win out over the good bacteria. Furthermore, stress also can disrupt the normal acidity of the stomach.

In one study, for example, in rats exposed to stress, the gastric acid concentration and levels of serum gastrin (a hormone responsible for gastric acid secretion) were significantly reduced compared to the non-stressed rats.3

Stomach acid is designed to protect the body from invasion by pathogenic organisms. When stress or other factors reduce the amount of gastric acid, the stomach is left vulnerable to invasion by Helicobacter pylori and E. Coli.

There are two main ways we can build up the health of our digestive tract. First, we must ensure that it is working properly by controlling lifestyle factors such as stress and diet and by ensuring the stomach has a plentiful supply of digestive enzymes. Second, we must protect against pathogens such as H. pylori and E. Coli by ensuring we are consuming adequate levels of proper nutrients and by consuming supplements that protect against these pathogens.

Digestive Enzymes and Probiotics

Constipation, diarrhea, bloating, and gas are all signs that the digestive tract is not functioning at its optimal best and may be deficient in a healthful supply of digestive enzymes.

Each of the five main digestive enzymes has a different role to play.

Amylase digests starch. Due to amylase’s role in breaking down carbohydrates, it’s not surprising that researchers have found that type 1 diabetics may suffer from an amylase deficiency, although this same deficiency wasn’t noted in type 2 diabetics.4 Vegetarians consuming low-tryptophan diets also may be deficient in this important enzyme.5

Protease breaks down the peptide bonds that join the amino acids in a protein, ensuring the amino acids are readily available to the body. In animals fed primarily grains and soy products, a combination of enzymes that included protease and cellulase improved nutrient utilization and growth performance.6

The enzyme lipase splits apart emulsified fats. In 100 subjects suffering from flatulence, pressure and pain in the stomach, nausea after meals, and belching, lipase and other proteolytic enzymes improved all of the above symptoms in 96 percent of the subjects.7 Lactase digests milk sugar, while cellulase helps break down plant and vegetable matter. These enzymes are secreted by the pancreas and are often referred to as pancreatic enzymes.

Without proper supplies of these enzymes, the body struggles to digest high-fat or high-starch meals. Pancreatic enzyme deficiencies also are associated with pancreatitis and Crohn’s disease.

Constipation, diarrhea, bloating, and gas also are signs that the balance between good and bad bacteria in the colon has been disrupted. Supplementing with probiotics such as Lactobacillus GG can replenish supplies of good bacteria within the intestinal tract. In a review of the literature, researchers evaluated studies investigating whether probiotics such as Lactobacillus GG can help alleviate antibiotic-caused diarrhea in children. They determined that treatment with probiotics compared with placebo reduced the risk of antibiotic-associated diarrhea from 28.5 percent to 11.9 percent.8

In another study, researchers concluded that Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis.9

H. Pylori

H. pylori is a common gastric bacterium associated with ulcers and an increased incidence of stomach cancer. Its presence is common in grocery store meat and seafood and is thought to be easily transmittable between family members.

Many in vitro studies have shown that various types of friendly bacteria, especially Lactobacillus GG, inhibit or kill H. pylori and prevent its adhesion to cells. In vivo models have demonstrated that pre-treatment with a probiotic can prevent H. pylori infections. Studies also have shown that administration of probiotics markedly reduces an existing infection.10

A review of human trials of adults and children colonized with H. pylori suggests that probiotics do not eradicate H. pylori but maintain lower levels of this pathogen in the stomach. The reviewers suggested that in combination with antibiotics, probiotics may increase the eradication rate and/or decrease adverse effects of H. pylori infection.11

Probiotics also can be used in conjunction with mastic gum (CeaseFire™). In vitro tests revealed that mastic was effective in killing 99.9 percent of H. pylori when tested against seven different strains, including three resistant to metronidazole. Of note was the finding that mastic was equally effective against the drug resistant strains of H. pylori, even at very low concentrations.12

E. Coli

As evidenced by the recent spinach scare, another bacterium that is especially menacing and damaging to the health of the digestive tract and the body as a whole is E. Coli. Although E. Coli is almost constantly present within the intestinal tract and usually remains nonpathogenic, outside the intestines it can pose a threat to health. Certain strains produce toxins that are pathogenic and can be fatal in the elderly and children who ingest them through contaminated food and water.

EpiCor™ has been shown to dramatically reduce the growth of E. Coli bacteria. At concentrations that continued all the way down to 1 part per billion, researchers noted total inhibition of E. Coli as well as Candida Tropicalis.

After conducting this study, it was concluded that EpiCor may provide protection against infection with coliform bacteria (a common cause of food poisoning) and candida. The study also indicated that EpiCor may support the growth of desirable mucosal flora in the intestinal tract.13

During in vitro studies, various strains of the probiotic Lactobacillus also inhibited E. Coli. One study showed that Lactobacillus could stop a pathogenic form of E. coli from adhering to colon cells and that it reduced E. Coli numbers.14

Conclusion

Wise men, poets and philosophers have long honored the process of digestion as the basis of good health, sound sleep and a happy attitude. Although the importance of the digestive tract is often overshadowed by the cardiovascular system, science supports the fact that a healthy digestive tract is just as important. Keeping the digestive tract free of pathogens and nourishing its health with digestive enzymes and probiotics is clearly one of the most crucial ways we can maintain our health.

References

1. Johns Hopkins Bayview Medical Center. JHBMC: Motility and Digestive Disorders: Statistic. Available from: http://www.jhbmc.jhu.edu.

2. Fallon Sally, Enig Mary, Primer on Digestion. Weston A. Price Foundation. Wise Traditions. Volume 5, Number 2, Summer 2004.

3. Azlina MF, Nafeeza MI, Khalid BA. A comparison between tocopherol and tocotrienol effects on gastric parameters in rats exposed to stress. Asia Pac J Clin Nutr. 2005;14(4):358-65.

4. Swislocki A, Noth R, Hallstone A, Kyger E, Triadafilopoulos G. Secretin-stimulated amylase release into blood is impaired in type 1 diabetes mellitus. Horm Metab Res. 2005 May;37(5):326-30.

5. Kushak RI, Drapeau C, Winter HS. Pancreatic and intestinal enzyme activities in rats in response to balanced and unbalanced plant diets. Plant Foods Hum Nutr. 2002 Fall;57(3-4):245-55.

6. Omogbenigun FO, Nyachoti CM, Slominski BA. Dietary supplementation with multienzyme preparations improves nutrient utilization and growth performance in weaned pigs. J Anim Sci. 2004 Apr;82(4):1053-61.

7. Carroccio A, Guarino A, Zuin G, Verghi F, Berni Canani R, Fontana M, Bruzzese E, Montalto G, Notarbartolo A. Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients. Aliment Pharmacol Ther. 2001 Oct;15(10):1619-25.

8. Szajewska H, Ruszczynski M, Radzikowski A. Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials.

J Pediatr. 2006 Sep;149(3):367-372.

9. Zocco MA, dal Verme LZ, Cremonini F, Piscaglia AC, Nista EC, Candelli M, Novi M, Rigante D, Cazzato IA, Ojetti V, Armuzzi A, Gasbarrini G, Gasbarrini A. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1567-74.

10. Hamilton-Miller JM. The role of probiotics in the treatment and prevention of Helicobacter pylori infection. Int J Antimicrob Agents 2003 Oct;22(4):360-6.

11. Gotteland M, Brunser O, Cruchet S. Systematic review: are probiotics useful in controlling gastric colonization by Helicobacter pylori? Aliment Pharmacol Ther. 2006 Apr 15;23(8):1077-86.

12. Huwez FU, Thirlwell D. Mastic Gum Kills Helicobacter pylori. N Engl J Med 1998; 339:1946, Dec 24, 1998.

13. Chris D. Meletis, ND. EpiCor™ Novel Immune System Enhancer Strengthens Microbial and Mutagenic Defense. Vitamin Research News. June 2006;20(6):1-4

14. Horosova K, Bujnakova D, Kmet V. Effect of lactobacilli on E. coli adhesion to Caco-2 cells in vitro. Folia Microbiol (Praha). 2006;51(4):281-2.