• The President's Desk  — The Cholesterol Controversy

• Enhancing Peak Male Performance with Scientifically Validated Botanicals  — 

• Oral Health and Heart Disease  — The Unexpected Connection

• Strengthening the GI Tract to Enhance Cognitive Health  — 

• Progesterone  — A Surprising New Use for a Popular Hormone

• Pet Corner  — Inflammatory Bowel Disease in Pets

• Ribonucleic Acid Part Three: Potential Therapeutic Uses  — Review of Clinical Experience with RNA

• New Research Suggests Resveratrol Improves Colon Health  — Breaking News
• Plant Extract May Support Weight Management  — Breaking News
• Melatonin Plays a Role in Mood Stabilization and Brain Health  — Breaking News
• Joint Supplement May Decrease Systemic Inflammation  — Breaking News
• Botanical May Alleviate Pain Sensitivity  — Breaking News
• Omega-3 Fatty Acids May Improve Heart Health  — Breaking News
• Select Antioxidants Support Bone Mineral Density  — Breaking News
• Quercetin Supports Athletic Endurance  — Breaking News

• Restless Legs, Venous Insufficiency
• Knee Surgery Support
• Hot Flashes
• Anemia and Lung Health
• CardioRhythm
• Alopecia in Young Child
• Pruritus
• Vitamin B12 Levels
• Liver Health
• Intestinal Support
• Metallic Taste in Mouth
• Extension Resveratrol

I want to thank all of our astute customers who emailed us regarding the fact that many people dispute high cholesterol as a cause of heart disease. Over the years, in various newsletter articles, we have made a concerted effort to cover all of the risk factors for the development of heart disease. We have extensively touched upon the link between the inflammatory marker C-reactive Protein and heart disease. We have also covered fibrinogen’s role.

The article, “Beyond Cholesterol Control: The Heart-Harming Consequences of Lowering Lipids While Neglecting Other Important Factors,” which appeared in the December 2008 issue of Vitamin Research News, stated “In the analysis of two large heart disease studies (Multiple Risk Factor Intervention Trial (MRFIT) and The Framingham Study) it has been statistically shown that half of those people that suffer heart attacks actually have cholesterol levels in the normal and low ranges.”

Clearly, cholesterol is only one chapter in the full story. As our past research shows, we are intimately aware of the complexities of the cardiovascular system and the fact that cholesterol in and of itself may not be as involved in the development of heart diseases as the conventional medical establishment may like us to believe.

Our research and development team continues to monitor the exciting new developments occurring in this area. One of those new developments is the emerging body of evidence showing that oxidized LDL cholesterol is injurious to the cardiovascular system. We are currently investigating specific antioxidants that can interfere with the LDL oxidation process in the body in the hope of offering a new formula to fight this damaging process. Meanwhile, to read more about LDL oxidation, please see the article “Lipid Oxidation: Optimal Heart Health Requires More Than Simple Cholesterol Reduction,” available on our website.

In the future, as new developments in cardiovascular health continue to emerge, we will share those developments with you, our valued customers.

We live in challenging times where chronic stress, environmental pollutants and a myriad of other burdens are eroding away health, wellness and sexuality. As the result of the accumulation of burdens that come with modern existence, an alarming 1 in 4 men at the age of 30 now have measurable low testosterone levels. This makes it difficult to survive, let alone thrive, when the very hormone that helps support inner health is fleeting.

Overt symptoms of low testosterone are believed to affect 50 percent of men with measurable low levels. Yet the slow erosion of wellness and zeal for life that occurs with low testosterone may be so gradual, that human perception is insufficient to note the change during the short term.

It is well known that testosterone levels decline with the passage of time, and the average man passively accepting the aging process may expect deterioration of performance. Without taking a proactive stance, men undergo such changes as a slow decrease in sex drive, diminished erectile strength, sleep disturbance, depressed mood, or lethargy.

In this article, I will discuss two mile markers of male wellness: libido and erectile performance.

Enhancing Male Performance

Erectile dysfunction affects 50 percent of men ages 40-70 in the United States and is considered an important public health problem by the National Institutes of Health. Clinically, I work with many men in their late twenties and early 30s that present to my office with decreased erectile performance or overt inability at times to perform. An even greater number of men report a “take it or leave it” approach when it comes to libido. These changes are symptoms of deeper health needs and serve as a barometer of ones wellness status.

Libido and pelvic responsiveness in both the male and female share many of the same biochemical pathways. Thus, much of what follows possesses relevance for both sexes.

Before I discuss the ways that both men and women can improve their libido and enhance intimacy performance, it’s important to acknowledge that maintaining healthy cardiovascular, neurological and mental wellness is also important for peak performance.

Natural Libido-Enhancing Strategies

A number of natural ingredients have been shown to affect the pathways involved in enhancing libido and improving sexual performance. Epimedium brevicornum, Tribulus terrestris, Panax ginseng, Ashwaghanda, grape seed extract, Eurycoma longifolia, pomegranate and green tea extracts (all found in the new AndroPrime^™ formula) have a synergistic role to play in helping men operate at peak performance.

Epimedium brevicornum

Epimedium brevicornum has been widely used for impotence, infertility, osteoporosis, cardiovascular diseases, amnesia, and senile functional diseases.¹ One of the mechanisms of action is that it supports nitric oxide levels, which are essential for arousal and erectile tissue engorgement. Nitric oxide (NO) is formed from the conversion of L-arginine by nitric oxide synthase (NOS), which exists in three isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). nNOS is expressed in penile neurons innervating the corpus cavernosum (CC), and eNOS has been identified primarily in both cavernosal smooth muscle of penileand clitoral tissue. Researchers have concluded that and extract of Epimedium relaxes the CC smooth muscle through multitargets in NO/cGMP/PDE 5 pathway and helps address erectile dysfunction.² Epimedium can prove very helpful as part of a male wellness protocol, relative to enhanced sexual performance.

Tribulus terrestris

Tribulus terrestris is another botanical commonly used to enhance libido. After conducting a study of Tribulus terrestris in rodents, researchers concluded, “Tribulus terrestris extract appears to possess aphrodisiac activity probably due to androgen increasing property of Tribulus terrestris.”³ Similar findings were found in another study on primates, where researchers noted that Tribulus increased testosterone in the animals, and another later study on rodents, leading researchers to conclude, “The increase in intracavernous pressure which confirms the proerectile aphrodisiac property of Tribulus terrestris could possibly be the result of an increase in androgen and subsequent release of nitric oxide from the nerve endings innervating the corpus cavernosum.”^4-5 Tribulus also is known to decrease levels of prolactin in women, which is important since increased prolactin is associated with reduced libido.⁶

Panax

Panax ginseng has long been known to help support the adrenal glands and thus help cope with stress, important because stress is known to affect sexual performance. In addition Panax ginseng also helps increase circulation as well as nitric oxide production.⁷ The ginsenosides contained in ginseng have been shown to cause a dose-dependent relaxation of the corpus cavernosal smooth muscle in rabbits by increasing nitric oxide release.^8-9 In a human study, 90 patients were divided into three groups and given Panax ginseng, a placebo, or the antidepressant drug trazodone orally. In the Panax ginseng group a significant improvement in erectile parameters such as penile rigidity, girth, duration of erection, improved libido, and patient satisfaction were reported. The overall therapeutic efficacy for erectile dysfunction was 60 percent for the Panax ginseng group but only 30 percent for the trazodone and placebo groups.¹⁰

A more recent, double-blind, placebo-controlled, crossover study confirmed these results. Forty-five men diagnosed with ED received either 900 mg Panax ginseng or placebo three times per day for eight weeks. The first eight weeks of treatment were followed by a two-week washout period, after which the patients switched groups—those who had initially received the placebo received ginseng and those who initially received ginseng received the placebo for an additional eight weeks. Researchers measured the efficacy of treatment through changes observed in indexes of erectile function, including the International Index of Erectile Function (IIEF). Mean scores on the IIEF for Panax ginseng were significantly higher than for placebo after eight weeks of each treatment. In addition, penile tip rigidity was significantly better after eight weeks of Panax ginseng compared to placebo.¹¹

Ashwagandha (Withania somnifera)

In clinical practice, Ashwagandha is an effective tool to support adrenal health. Stressed patients routinely report noticing an increased sense of well being with its use. An intriguing rat study evaluated the combined effects of Withania somnifera and Panax ginseng extracts. The two extracts were compared for their ability to attenuate some deleterious impact of chronic stress (CS). Both botanicals were able to decrease the number and severity of CS-induced ulcers, reverse CS-induced inhibition of male sexual behavior, and inhibit the adverse effects of CS on retention of learned tasks. Both botanicals also reversed CS-induced immunosuppression, but only the Withania extract increased peritoneal macrophage activity in the rats.¹² This latter observation emphasizes the importance that can be gained by blending synergistic botanicals.

Grape Seed Extract

Maintaining the 60,000 miles of blood vessels and overall integrity of the circulatory system is essential. It is this long-term, broader thinking that helps preventively protect the body from needing to depend on what can be termed “reactionary” medicine. Several epidemiological studies suggest that the regular consumption of foods and beverages rich in flavonoids is associated with a reduction in the risk of several pathological conditions ranging from hypertension to coronary heart disease, stroke and dementia. Grape seed is one of the major polyphenols shown to have some of these effects in humans.¹³

Grape seed extract is emerging as a nutrient that has profound effects on nitric oxide production. Studies investigating grape seed’s ability to support healthy blood pressure levels have determined its mechanism of action is partly due to its ability to raise nitric oxide levels. As noted earlier, nitric oxide is essential for arousal and erectile tissue engorgement.^14-15

Eurycoma longifolia

Eurycoma longifolia, often called Long Jack, has a long history of use as a performance enhancing substance. In one study, extracts from E. longifolia Jack were orally administered to rats twice daily for 10 days. Testosterone was used as a positive control. Results showed that E. longifolia Jack produced a dose-dependent increase in sexual performance of the treated animals. The authors reported, “The present study therefore gives further evidence of the folk use of E. longifolia as an aphrodisiac.”¹⁶

Pomegranate Extract

A study using a rabbit model of arteriogenic erectile dysfunction (ED) measured the effect of pomegranate juice (PJ) concentrate on intracavernous blood flow and penile erection. The researchers found eight weeks administration of PJ concentrate daily significantly increased intracavernous blood flow and smooth muscle relaxation.¹⁷ These findings are preliminary, yet the results are promising.

As with many botanicals, there is not merely one potential clinical application. For instance, studies have shown that pomegranate can block the conversion of testosterone to estrogen, a process controlled by the aromatase enzyme. Pomegranate inhibited aromatase activity by 60–80 percent thus helping protect estrogen sensitive tissues including prostate and breast tissue.¹⁸

Green Tea Extract

Green tea extract is another nutrient important for male health. In vitro and animal studies have shown that green tea is a natural aromatase inhibitor that modulates estrogen synthesis.^19-20 This effect can play a role in libido enhancement and overall male health.

Antioxidant Protection

One of the additional ways that ED begins to manifest is from the accumulation of unquenched oxidative products in erectile tissue.²¹ Antioxidant therapy is important for overall wellness and can prove useful prophylactic tool for preventing smooth muscle dysfunction and fibrosis in ED. Many of the ingredients mentioned above, including grape seed and pomegranate, also act as potent antioxidants.

New AndroPrime^™

In addition to incorporating all the ingredients mentioned above, the new AndroPrime formula also contains Bioperine^® a proprietary black pepper extract. Bioperine was incorporated into AndroPrime to augment the effectiveness of the individual constituent herbs and the overall synergy of the formula.

Conclusion

It is clear that ultimate sexual functioning depends on a strong and well-nourished body that provides the ability to attain or maintain an erection. Epimedium brevicornum, Tribulus terrestris, Panax ginseng, Ashwaghanda, grape seed extract, Eurycoma longifolia, and pomegranate extract along with Bioperine (all found in the new AndroPrime^™) can provide synergistic support for optimal male performance.

Editor’s Note: Dr. Meletis is author of the book Better Sex Naturally, published by HarperCollins and co-author of His Change of Life, published by Greenwood Publishing.

References

1. Li HB, Chen F. Separation and purification of epimedin A, B, C, and icariin from the medicinal herb Epimedium brevicornum maxim by dual-mode HSCCC. J Chromatogr Sci. 2009; 47(5):337-40.

2. Chiu JH, Chen KK, Chien TM, Chiou WF, Chen CC, Wang JY, Lui WY, Wu CW Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway. Int J Impot Res. 2006 Jul-Aug;18(4):335-42.

3. Gauthaman K, Adaikan PG, Prasad RN. Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats. Life Sci. 2002 Aug 9;71(12):1385-96.

4. Gauthaman K, Ganesan AP, Prasad RN. Sexual effects of puncturevine (Tribulus terrestris) extract (protodioscin): an evaluation using a rat model. J Altern Complement Med.. 2003 Apr;9(2):257-65.

5. Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction—an evaluation using primates, rabbit and rat. Phytomedicine. 2008 Jan;15(1-2):44-54.

6. Dean W. The Neuroendocrine Theory of Aging Chapter 5. The Female Reproductive Homeostat. Vitamin Research News. December 1, 2005; 19(11).

7. Chen X, et al. Extracts of Ginkgo bilobaand ginsenoside exert cerebral vasodilation via a nitric oxide pathway. Clin Exp Pharmacol Physiol. 1997;24:958–959.

8. Choi YD, Xin ZC, Choi HK. Effect of Korean red ginseng on the rabbit corpus cavernosal smooth muscle. Int J Impot Res. 1998;10:37-43.

9. Kim HJ, Woo DS, Lee G, Kim JJ. The relaxation effects of ginseng saponin in rabbit corporal smooth muscle: is it a nitric oxide donor? Br J Urol. 1998;82:744-748.

10. Choi HK, Seong DH, Rha KH. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impot Res. 1995;7:181-186.

11. Hong B, Ji YH, Hong JH, et al. A double-blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. J Urol. 2002;168:2070-2073.

12. Bhattarcharya SK, Muruganandam AV. Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav 2003;75:547-53.

13. Ghosh D, Scheepens A. Vascular action of polyphenols. Mol Nutr Food Res. 2009 Mar;53(3):322-31.

14. Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C. Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond). 2008 Feb;114(4):331-7.

15. Zhang TX, Niu CQ, Hu JM, Liu H, Jing HE. Vasorelaxational effects of procyanidins on rabbit aorta in vitro and decreasing arterial blood pressure in vivo. Zhongguo Zhong Yao Za Zhi. 2008 Jul;33(14):1720-3.

16. Ang HH, Cheang HS, Yusof AP. Effects of Eurycoma longifolia Jack (Tongkat Ali) on the initiation of sexual performance of inexperienced castrated male rats. Exp Anim. 2000 Jan;49(1):35-8.

17. Azadzoi K, Schulman R, Aviram M, Siroky M. Oxidative Stress in Arteriogenic Erectile Dysfunction: Prophylatic Role of Antioxidants  The Journal of Urology, 2005(174) 1:386-393.

18. Kim ND, Mehta R, Yu W, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat. Feb 2002;71(3):203-217.

19. Monteiro R, Azevedo I, Calhau C. Modulation of aromatase activity by diet polyphenolic compounds. J Agric Food Chem. 2006 May 17;54(10):3535-40.

20. Satoh K, Sakamoto Y, Ogata A, Nagai F, Mikuriya H, Numazawa M, Yamada K, Aoki N. Inhibition of aromatase activity by green tea extract catechins and their endocrinological effects of oral administration in rats. Food Chem Toxicol. 2002 Jul;40(7):925-33.

21. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol 2005;174:386-393.

Periodontal diseases are oral infections that affect the gums and bone that surround and support the teeth. Gingivitis is the early stage of gum disease in which the gums become swollen and red and may bleed easily. Periodontitis is the more serious type of gum disease in which the gums can pull away from the tooth, bone loss can occur, and the teeth may loosen or fall out. Periodontal disease is caused by oral bacteria, which form a film known as plaque on the teeth and may harden to form tartar over time. When tartar builds up, it can spread below the gum line causing infection and inflammation in the gum tissue. According to the Centers for Disease Control and Prevention (CDC), gum disease affects one in seven adults aged 35 to 44 years and one in four adults aged 65 years and older.¹

Heart disease is the leading cause of death in the United States. In 2005, more than 27 percent of deaths in the United States were caused by heart disease. Coronary heart disease (CHD), the principal type of heart disease, resulted in over 68 percent of these deaths. Research indicates that an estimated 37 percent of adults have at least 2 of the risk factors associated with heart disease including high blood pressure, high cholesterol, diabetes, current smoking, physical inactivity, and obesity.²

Recent research has uncovered yet another independent risk factor for heart disease—poor oral health. Numerous studies indicate that gum disease is associated with heart disease,³ and chronic periodontitis is an independent risk factor for coronary artery disease.⁴

The Gum-Heart Link

There is a large body of research to establish the connection between oral health and heart disease. One study found that periodontal disease was present in over 84 percent of patients with coronary atherosclerotic heart disease (CAD), but present in less than 23 percent of subjects without CAD.⁵ Data also indicates that periodontal disease is significantly associated with hypertension and risk for myocardial infarction (heart attack).⁶ Research has shown that periodontal disease severity directly correlates to the extent of coronary lesions.⁷ In addition, researchers have uncovered a genetic link between CHD and periodontal disease. A genetic variation was found in a specific location (locus) on chromosome number 9, which is strongly associated with both aggressive periodontitis and CHD.⁸

Evidence suggests that oral infections result in systemic exposure to pathogenic oral bacteria and increased levels of inflammatory markers, which could contribute to the pathology of CHD and atherosclerosis.⁹ Elevated levels of inflammatory markers such as C-reactive protein (CRP) and fibrinogen are associated with CHD. Research also indicates that many patients with moderate to severe periodontal disease also exhibit elevated levels of CRP¹⁰ and fibrinogen,¹¹ suggesting that a systemic inflammatory process may be the physiological link between these conditions.

Researchers have also found the presence of oral bacteria such as Streptococcus mutans in cardiovascular tissues. In fact, in subjects with Streptococcus mutans in dental plaques, 78 percent also had the same bacteria in cardiovascular tissue. Thus, the investigators concluded that infections caused by oral bacteria may be etiologic factors for the development of cardiovascular diseases.¹² One study showed that 65 percent of patients had pathogens most frequent in severe chronic periodontitis present in coronary vessels. In 50 percent of the subjects, pathogens frequently found in severe chronic periodontitis were also found in atherosclerotic plaque.¹³ Research has also shown that elevated levels of antibodies to common oral pathogens were more common in subjects with a history of heart attack compared to healthy controls.¹⁴

In another study, subjects with periodontal disease and elevated lipid levels (hyperlipidemia) were treated with periodontal therapy for 3 months. The subjects were evaluated for periodontal health and serum lipid levels at the initiation of the study and after 3 months of treatment. The results showed that after 3 months of treatment all of the periodontal measurements improved. What is most interesting, however, is that the total cholesterol and triglyceride levels in these patients also were reduced significantly and high-density lipoprotein (HDL) cholesterol levels significantly increased. In fact, 8 out of the 20 subjects showed serum lipid levels reduced into the normal range.

Thus, the study authors concluded, “Our observation indicated that periodontal initial therapy could reduce the serum lipid levels of patients with both periodontitis and hyperlipidemia, which might be helpful for decreasing risk of cardiovascular disease such as coronary heart disease.”¹⁵

Natural Support for Gum Health

As the above research indicates, supporting the health of the gums is important not only to optimize oral health, but also to reduce heart disease risk. A couple of natural strategies can be used to maximize periodontal health.

Xylitol is a naturally occurring 5-carbon sugar alcohol that can be used as a sugar substitute. Unlike most sugars, xylitol has been shown to improve oral health and decrease dental caries. Most sugars act as a substrate for oral bacteria, which lower the pH (increase acidity) allowing the bacterium to thrive. These bacterium increase the acidity of the saliva and plaque, which induces tooth demineralization and decay. Xylitol, however, has been shown to significantly reduce plaque acidogenicity.¹⁶ Studies have shown that xylitol ingestion can significantly reduce tooth decay and the number of decayed teeth.¹⁷ In one study, researchers studied the effect of chewing xylitol gum on the oral bacterium Streptococcus mutans over one year duration. The study showed that chewing xylitol gum decreased the number and size of the bacterial colonies, decreased the ability of the bacterium to adhere to surfaces, and decreased the secretion of polysaccharides, which are endotoxins on the outer membrane of some bacteria.¹⁸

Another study evaluated the effect of xylitol on pro-inflammatory cytokines (signaling molecules) in order to determine xylitol’s effect on periodontal health. Periodontitis is characterized by lipopolysaccharides from oral bacteria inducing inflammatory cytokine secretion, which damages the gingival tissue. In this study, cells were stimulated with lipopolysaccharides from the oral pathogenic bacterium Porphyromonas gingivalis. This resulted in an increase in pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and activation of the pro-inflammatory transcription factor nuclear factor (NF)-kappaB. Pre-treatment of the cells with xylitol inhibited the gene expression and protein synthesis of TNF-alpha and IL-1beta as well as suppressed the activation of NF-kappaB. In addition, xylitol inhibited growth of Porphyromonas gingivalis.¹⁹

The researchers concluded, “Taken together, these findings suggest that xylitol may have good clinical effect not only for caries but also for periodontitis by its inhibitory effect on the LPS-induced inflammatory cytokine expression.”

Another effective natural strategy for supporting gum health is hyaluronic acid (HA). HA is a glycosaminoglycan (GAG) polypeptide chain of disaccharide units found in the extracellular matrix that surrounds and supports tissue cells. Hyaluronic acid is found in large concentrations in connective tissues such as the joints and skin. This molecule supports surrounding tissues, facilitating cell migration and wound healing, plays a role in cell signaling, helps maintain cellular structure and function, acts as a lubricant, and exhibits antioxidant properties. Additionally, high molecular weight hyaluronic acid also acts as an anti-inflammatory molecule.²⁰

Hyaluronic acid has been shown to be beneficial in supporting gum health. It is the most abundant high molecular weight GAG in the extracellular matrix of soft periodontal tissues. Studies indicate that hyaluronic acid exhibits beneficial anti-inflammatory and antibacterial activity in the treatment of gingivitis and periodontitis.^21-22 Hyaluronic acid has also been shown to improve wound healing in oral lesions such as aphthous ulcers, or canker sores,²³ and assist healing after tooth extraction.²⁴ Additionally, hyaluronic acid has been shown to improve hypo-salivation (also called dry mouth or xerostomia). Patients suffering from hypo-salivation have been shown to have decreased levels of hyaluronic acid in their saliva resulting in decreased oral mucosa lubrication.²⁵ Other researchers confirmed that treatment of hypo-salivation with hyaluronic acid improved symptoms associated with dry mouth.²⁶ In patients with oral lichen planus HA also significantly reduced soreness scores compared with placebo.²⁷

A new high molecular weight HA lozenge provides a highly bioavailable form of this nutrient that is well absorbed through the oral mucosa. This delivery form is ideal for individuals who want to promote oral health.

Conclusion

Increasing evidence supports the association between gum disease and heart disease and that treatment of periodontal disease has beneficial effects on cardiovascular disease risk factors. Thus, therapies to enhance periodontal health such as xylitol gum and mints and hyaluronic acid lozenges may provide additional options to address the overwhelming prevalence of heart disease in the United States.

References

1. Centers for Disease Control and Prevention. Adult Oral Health. Available at: http://www.cdc.gov/OralHealth/topics/adult.htm. Accessed on: 07-11-09.

2. Centers for Disease Control and Prevention. Heart Disease Facts and Statistics. Available at: http://www.cdc.gov/heartdisease/statistics.htm. Accessed on: 07-11-09.

3. Cronin A. Periodontal disease is a risk marker for coronary heart disease? Evid Based Dent. 2009;10(1):22.

4. Zhang YM, Zhong LJ, He BX, et al. Study on the correlation between coronary heart disease and chronic periodontitis. Zhonghua Liu Xing Bing Xue Za Zhi. 2006 Mar;27(3):256-9.

5. Liu P, Zhang Y, Wang SJ, et al. Correlation between periodontal disease and coronary atherosclerotic heart disease. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2006 Apr;28(2):169-72.

6. Holmlund A, Holm G, Lind L. Severity of periodontal disease and number of remaining teeth are related to the prevalence of myocardial infarction and hypertension in a study based on 4,254 subjects. J Periodontol. 2006 Jul;77(7):1173-8.

7. Amabile N, Susini G, Pettenati-Soubayroux I, et al. Severity of periodontal disease correlates to inflammatory systemic status and independently predicts the presence and angiographic extent of stable coronary artery disease. J Intern Med. 2008 Jun;263(6):644-52.

8. Schaefer AS, Richter GM, Groessner-Schreiber B, et al. Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis. PLoS Genet. 2009 Feb;5(2):e1000378.

9. Karnoutsos K, Papastergiou P, Stefanidis S, et al. Periodontitis as a risk factor for cardiovascular disease: The role of anti-phosphorylcholine and anti-cardiolipin antibodies. Hippokratia. 2008 Jul;12(3):144-9.

10. Liu J, Wu YF, Ding Y, et al. Serum C-reactive protein levels and lipid profiles concentrations in moderate to severe periodontitis and coronary heart disease: a comparative study. Zhonghua Kou Qiang Yi Xue Za Zhi. 2009 Mar;44(3):150-4.

11. Ge S, Wu YF, Liu TJ, et al. Study of the correlation between moderately and severely chronic periodontitis and coronary heart disease. Hua Xi Kou Qiang Yi Xue Za Zhi. 2008 Jun;26(3):262-6.

12. Nakano K, Nemoto H, Nomura R, et al. Detection of oral bacteria in cardiovascular specimens. Oral Microbiol Immunol. 2009 Feb;24(1):64-8.

13. Zaremba M, Górska R, Suwalski P, et al. Periodontitis as a risk factor of coronary heart diseases? Adv Med Sci. 2006;51 Suppl 1:34-9.

14. Lund Håheim L, Olsen I, Nafstad P, et al. Antibody levels to single bacteria or in combination evaluated against myocardial infarction. J Clin Periodontol. 2008 Jun;35(6):473-8.

15. Duan JY, Ou-Yang XY, Zhou YX. Effect of periodontal initial therapy on the serum level of lipid in the patients with both periodontitis and hyperlipidemia. Beijing Da Xue Xue Bao. 2009 Feb 18;41(1):36-9.

16. Splieth CH, Alkilzy M, Schmitt J, et al. Effect of xylitol and sorbitol on plaque acidogenesis. Quintessence Int. 2009 Apr;40(4):279-85.

17. Milgrom P, Ly KA, Tut OK, et al. Xylitol pediatric topical oral syrup to prevent dental caries: a double-blind randomized clinical trial of efficacy. Arch Pediatr Adolesc Med. 2009 Jul;163(7):601-7.

18. Lee YE, Choi YH, Jeong SH, et al. Morphological changes in Streptococcus mutans after chewing gum containing xylitol for twelve months. Curr Microbiol. 2009 Apr;58(4):332-7.

19. Han SJ, Jeong SY, Nam YJ, et al. Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide from Porphyromonas gingivalis. Clin Diagn Lab Immunol. 2005 Nov;12(11):1285-91.

20. Ialenti A, Di Rosa M. Hyaluronic acid modulates acute and chronic inflammation. Agents Actions. 1994;43:44-7.

21. Sukumar S, Drízhal I. Hyaluronic acid and periodontitis. Acta Medica (Hradec Kralove). 2007;50(4):225-8.

22. Pistorius A, Martin M, Willershausen B, et al. The clinical application of hyaluronic acid in gingivitis therapy. Quintessence Int. 2005 Jul-Aug;36(7-8):531-8.

23. Lee JH, Jung JY, Bang D. The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: comparison between recurrent aphthous ulcers and the oral ulcers of Behçet’s disease. J Eur Acad Dermatol Venereol. 2008 May;22(5):590-5.

24. Mendes RM, Silva GA, Lima MF, et al. Sodium hyaluronate accelerates the healing process in tooth sockets of rats. Arch Oral Biol. 2008 Dec;53(12):1155-62.

25. Higuchi Y, Ansai T, Awano S, et al. Salivary levels of hyaluronic acid in female patients with dry mouth compared with age-matched controls: a pilot study. Biomed Res. 2009 Feb;30(1):63-8.

26. Yuan J, Tohara H, Mikushi S, et al. The effect of “Oral Wet” for elderly people with xerostomia—the effect of oral rinse containing hialuronan. Kokubyo Gakkai Zasshi. 2005 Mar;72(1):106-10.

27. Nolan A, Badminton J, Maguire J, Seymour RA. The efficacy of topical hyaluronic acid in the management of oral lichen planus. J Oral Pathol Med. 2009 Mar;38(3):299-303.

At first glance, the intestinal tract and the brain seem like unlikely allies in the support of proper cognitive and emotional health. They are located at opposite ends of the body and seem to have widely different functions. Yet, emerging research indicates that both the gut and the brain play a beneficial role in cognitive health. New studies are showing that variations in gut microflora may be associated with changes in the normal functioning of the nervous system, a fact that is revealing new possibilities for probiotic bacteria in regards to brain health.

Normal gastrointestinal health relies on a properly functioning brain-gut axis, in which serotonin facilitates communication between the enteric nervous system (ENS) and the rest of the gut, driving functions such as gut motility and pain perception. Serotonin is a predominant signaling molecule in this process with up to 95 percent of the body’s serotonin found in the gut. Consequently, it’s not surprising that if the gastrointestinal system becomes upset, well being and cognitive health may suffer.

The gastrointestinal (GI) tract is a delicately balanced system in many ways and any breach in its natural defenses or normal function can create problems that extend beyond the gut to the brain and elsewhere. Research shows that defects in serotonin signaling can contribute to the pathophysiology of irritable bowel syndrome (IBS) and other gut motility disorders.¹

In addition to serotonin, an optimal functioning GI tract requires a healthy population of naturally occurring probiotic (or friendly) bacteria, such as Lactobacilli and Bifidobacteria, which play a key role in preventing the overgrowth of harmful enterobacteria. An absence of probiotic bacteria has adverse effects not only locally in the gut but has also been shown to affect the central hypothalamus-pituitary-adrenal axis and monoaminergic activity, both of which have been implicated in the etiology of depression.² In a paper entitled, “Mood and gut feelings,” Canadian researchers present evidence that variations in the composition of gut microbes may be associated with changes in the normal functioning of the nervous system.³

If the delicate balance of the microflora environment is upset, toxic bacteria can out-compete health-promoting probiotic bacteria, causing not only gas and bloating, but also inflammation of the gut’s mucosal lining – a single layer of epithelial cells held together by tight junctions that provide a barrier between the GI tract and the bloodstream. Chronic inflammation of the mucosal lining increases total burden of absorbed foreign material, be it protein, microorganisms, or toxins. The release of unwanted material into the rest of the body in this way is referred to as the “leaky gut” syndrome and is an emerging factor in the development of a number of neuropsychological illnesses as highlighted below.

GI Diseases and the Cognitive Connection

Scientists began establishing a link between the gut and the brain during studies of irritable bowel syndrome and inflammatory bowel disease patients. Irritable bowel syndrome (IBS) is a debilitating intestinal disorder that affects up to 25 percent⁴ of the American population and is one of the most common conditions seen in primary care settings.⁵ It is characterized by intermittent abdominal pain, altered bowel habits, and other symptoms such as bloating that can have a profound impact on emotional health and quality of life.⁶ Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine and includes such disorders as ulcerative colitis and Crohn’s disease.

A new study released in June of this year found that patients with inflammatory bowel disease have an increased incidence of verbal IQ deficit (a reduced ability to recall words). The researchers found evidence of a verbal IQ decrement in both IBD and IBS patients when measured against both healthy controls and against the patients’ own pre-disease IQ scores. The verbal IQ deficit was particularly pronounced in the inflammatory bowel disease patients.⁷

Furthermore, psychiatric disorders especially major depression and anxiety can be seen in up to 94 percent of IBS patients, and the disorder is frequently interconnected with fibromyalgia and chronic fatigue syndrome.⁸ The treatments used for IBS patients often are tied as much to emotional health as to gut health. For example, cognitive-behavioral therapy is known to be effective in IBS sufferers.⁹

IBS sufferers demonstrate significantly lower concentrations of the probiotics Bifidobacteria and Lactobacilli compared with healthy controls.¹¹ While the etiology of IBS remains unclear, researchers believe both inflammatory changes¹⁰ and modifications in the normal gut flora⁶ play a role and that probiotics may favorably alter that milieu.

Depression

The role of the leaky gut syndrome in depression is supported by mounting research that has uncovered higher levels of serum antibodies against toxins from pathogenic enterobacteria in patients with depression compared with healthy controls.^12-15 In one study, researchers noted the differences to be so significant that the results could actually be used to diagnose depression with an accuracy rate of 90 percent.¹⁴

Chronic Fatigue Syndrome

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.¹⁶ More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.¹⁶ More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.¹⁶ As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.¹⁷ Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.¹⁶

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.¹⁸ Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.¹⁸ This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.¹⁹ While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.¹⁶

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.^10,20 However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.²

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.²¹

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO^™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.²² In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.²³ Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.²⁴ DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.^25-26

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;²⁷ Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;²⁸ Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;²⁹ Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;³⁰ Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;²⁸ Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;³¹ and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56.

9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Progesterone has long been recognized for its important role in female health. It is commonly used to compensate for the imbalance in progesterone and estrogen and has been clinically beneficial in weight gain, fatigue, loss of libido, depression, headaches, joint pain and mood swings as well as uterine fibroids, menstrual problems, autoimmune disorders, and bone loss. In males, progesterone is used to support prostate health. Over the last several years, however, exciting new research has begun to unveil another potential property of progesterone—protecting the brain.

New studies are showing that progesterone’s effects stretch beyond the reproductive and endocrine systems. In fact, researchers now know that progesterone is produced in the brain by neurons and glial cells in the central and peripheral nervous system of both male and females.¹

Progesterone is considered a sex hormone and occurs in female mammals at higher rates than in males, although males produce this hormone as well in lesser quantities. Scientists accidentally discovered that it may be helpful in brain function when they noticed that when brain injury was induced in rodents, many female rats experienced no cognitive deficits even though males suffered impaired brain function. Furthermore, gender differences in stroke outcome, with women being protected from cerebrovascular disease more than men, have implicated progesterone, a hormone often associated with females, in brain health.² This led to a series of experiments with intriguing results.

Progesterone and the Brain

Laboratory data strongly show that progesterone treatment after traumatic brain injury reduces edema, improves outcomes, and restores blood-brain barrier function.³

A new study appearing in the August 2009 Brain Research Bulletin followed up on previous animal studies that demonstrate progesterone (PROG) significantly reduces cerebral edema and enhances functional recovery from traumatic brain injury (TBI) and stroke in several animal models.⁴

This new study was designed to investigate the inhibitory effects of progesterone on inflammatory response after stroke and the hormone’s influence on the structure of the blood-brain barrier (BBB). Researchers administered 8 mg/kg of progesterone by intraperitoneal injection 1 hour and 6 hours after permanent occlusion of middle cerebral artery was induced in rats. Additional injections of 15 mg/kg were administered subcutaneously once per day after the initial dose. The researchers then measured expression of the inflammatory marker tumor necrosis factor-alpha (TNF-alpha). They also measured levels of matrix metalloproteinase-9 (MMP-9). Recent research suggests an active role of MMPs in the development of aortic aneurysm. Excess MMPs degrade the structural proteins of the aortic wall.

The results showed that progesterone reduced levels of the inflammatory marker TNF-alpha and levels of MMP-9. Progesterone also improved markers of brain health and the health of the blood brain barrier.⁴ This led the study authors to conclude, “Our findings reveal that PROG [progesterone] inhibited the inflammatory response after experimental stroke and mitigated the severity of brain damage, suggesting a role for PROG in the integrity of the BBB [blood brain barrier] and subsequent edema formation following cerebral ischemia.”

Another group of researchers replicated a typical human stroke in 24 rats by blocking (occluding) the middle cerebral artery. The researchers then injected 8 mg/kg of progesterone or a control at 1 hour post-occlusion followed by subcutaneous injections at 6, 24 and 48 hours. Progesterone-treated rats showed a substantial reduction (54 percent) in the volume of the infarct compared to controls. In addition, there was a significant improvement in ability to remain on an accelerating rotarod and increased grip strength observed in the rats treated with progesterone compared to controls.⁵

According to the study authors, “Taken together, these data indicate that PROG is beneficial in one of the best-characterized models of stroke, and may warrant further testing in future clinical trials for human stroke.”

Rat models of traumatic brain injury have yielded similar results. Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in young people. Researchers recently conducted a study to investigate the inhibitory effect of progesterone on inflammatory response after traumatic brain injury. Progesterone was injected intraperitoneally using rats as a model of traumatic brain injury, and researchers then detected the expression of three inflammation-related factors: nuclear factor kappa B p65 (NFkappaB p65), glial fibrillary acidic protein (GFAP), and tumor necrosis factor-alpha (TNF-alpha). The water content of injured brain was also examined.

The inflammatory markers NFkappaB p65, GFAP, and TNF-alpha were increased in all injured animals. In rats treated with progesterone, however, the expression level of NFkappaB p65 and TNF-alpha were reduced significantly in comparison with vehicle-treated rats. Progesterone also reduced the water content of injured brain and the lesion volume. In addition, progesterone-treated injured rats showed significant improvements in the Neurological Severity Score test, compared with controls.⁶

The researchers concluded, “Progesterone inhibits the inflammatory response after experimental traumatic brain injury and mitigates the severity of brain damage.”

Studies conducted to date indicate progesterone appears to exert its brain-protective effects by protecting or rebuilding the blood-brain barrier, decreasing development of cerebral edema, down-regulating the inflammatory cascade, and limiting cellular necrosis and apoptosis.¹

The studies in animals have been so promising that researchers have begun ongoing human trials for progesterone treatment after TBI.³

Although the research published to date has focused primarily on progesterone’s effects on blunt traumatic brain injury and strokes, there is evidence that the hormone affords protection from several forms of acute central nervous system injury, including penetrating brain trauma, anoxic brain injury, and spinal cord injury.¹

Conclusion

The fact that progesterone has shown such promise in supporting brain damage indicates that it may also be a valuable tool in enhancing general brain health. We believe the most efficient delivery method for progesterone is through the use of a topical cream.

References

1. Stein DG, Wright DW, Kellermann AL. Does progesterone have neuroprotective properties? Ann Emerg Med. 2008 Feb;51(2):164-72.

2. Gibson CL, Coomber B, Rathbone J.  Is Progesterone a Candidate Neuroprotective Factor for Treatment following Ischemic Stroke? Neuroscientist. 2009 Apr 9. Published Online Ahead of Print.

3. Herson PS, Koerner IP, Hurn PD. Sex, sex steroids, and brain injury. Semin Reprod Med. 2009 May;27(3):229-39.

4. Wang J, Jiang C, Li X, Liu C, Cheng N, Hao Y. The protective mechanism of progesterone on blood-brain barrier in cerebral ischemia in rats. Brain Res Bull. 2009 Aug 14;79(6):426-30.

5. Ishrat T, Sayeed I, Atif F, Stein DG. Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats. Brain Res. 2009 Feb 27;1257:94-101.

6. Pan DS, Liu WG, Yang XF, Cao F. Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury. Biomed Environ Sci. 2007 Oct;20(5):432-8.

Inflammatory Bowel Disease (IBD) is a problem that can occur in both dogs and cats. Typically, these animals are not doing well, may have chronic diarrhea that responds poorly or is non responsive to treatment. These animals may become irritable and prefer that they not be handled. In cats, the primary sign may be hacking up hairballs.

To get to an actual diagnosis, we need to rule out intestinal parasites (worms) as a cause. Included in the parasite list are the single cell parasites such as Giardia. Other causes may be some specific bacteria or viruses and thankfully, on a more rare occasion, cancer in the bowel tract.

To diagnosis IBD, we normally run a full blood profile, take x-rays of the abdomen and may follow that with an ultrasound scan, do several fecal exams to rule out the parasites and finally, get a biopsy of the bowel tract.

Treatment falls in the area of anti-inflammatory medicine in Western medicine. This would include various cortisone preparations such as hydrocortisone, prednisone, prednisolone, dexamethasone and triamcinolone. These may be tried alone or in combination with some of the chemotherapy agents such as cyclosporine. Antibiotics such as metronidazole or tylosin may be used by themselves or in conjunction with the above drugs.

I have had several animals, primarily cats, which were non-responsive to drug therapy. At that time, I was using N-acetyl-glucosamine by itself. I actually had better luck controlling the IBD with the N-acetyl-glucosamine (NAG) by itself than I did with the drugs. Consequently, for quite a few years, I have gone to NAG as my primary treatment even if I just suspected IBD and had already finished ruling out other causes.

I believe we have a better preparation now than just using the NAG and a better understanding of why it helped. Lectin Lock^™ is a combination of NAG, bladderwrack, okra powder, D-mannose, mucin, sodium alginate and pepsin. Each of these ingredients plays a role in capturing lectins and moving them on through the bowels and out of the body. The lectin is a small protein molecule that has numerous functions, some good, some not.

Foods with high concentrations of lectins, such as beans, cereal grains, seeds and nuts may be harmful if consumed in excess. Adverse effects include allergic reactions, nutritional deficiencies and immune reactions. For those animals that have reactions that led to IBD, using Lectin Lock may pick up and carry those aggravating lectins on through and out of the system.

For nearly twenty-five years—from the mid 1950s to the late 70s—New York physician Benjamin Frank, M.D., pioneered the use of nucleic acids in the therapy of aging and chronic degenerative diseases. Dr. Frank reported the results of his research and clinical experience in four books published during this time (Fig.1).

His experiences were reviewed in two previous articles in Vitamin Research News that described the life-extending effects of RNA given to experimental animals, and the proposed mechanism of action for RNAs anti-aging effects.^1-2

Dr. Frank found that RNA had a number of profound effects: 1) anti-aging (including reduced skin wrinkling and increased skin elasticity); 2) energizing; 3) anti-anoxia (oxygen sparing); 4) anti-low temperature and freezing (as evidenced by increased survival of experimental animals subject to low temperatures); 5) anti-viral; and 6) cognitive enhancing.

This third article describes a number of conditions that are helped by RNA therapy, and some specific RNA protocols Dr. Frank used for these conditions.

Atherosclerosis, Coronary Artery Disease

Dr. Frank was one of the first researchers to recognize that carbohydrates-especially refined carbohydrates (i.e., sugars)—are major contributing factors in elevating trigylcyeride levels and the progression of atherosclerosis. Dr. Frank also believed that the high concentration of nucleic acids found in fish-especially sardines-were the primary reason for the coronary-artery-disease-preventing effects of a high-fish diet. This view ran counter to the prevailing theory of the time that attributed these benefits to the high concentrations of Omega-3 fatty acids contained in fish.

Consequently, Dr. Frank routinely prescribed high-dose nucleic acids for atherosclerosis. Doses were varied, depending on the severity of the condition, and the response of a given individual to the treatment. Dr. Frank often treated patients with doses as high as 10 grams per day, up to three times per week, although in mild cases he observed positive effects with doses as low as 500 to 1,000 mg per day.

The first benefit commonly noted by his patients was increased exercise tolerance, along with decreased shortness of breath with exertion and the disappearance of heart (anginal) pains. These effects were usually reported within two weeks of supplementation.

Dr. Frank observed that patients diagnosed with hypercholesterolemia experienced a significant lowering of their blood cholesterol after one or two months of supplementation with nucleic acids, with little or no change in other dietary habits. He believed that lipid abnormalities involved in atherosclerosis were due to mitochondrial dysfunction, caused by a dietary deficiency of nucleic acids.

Further, he believed that the cholesterol-lowering effect of nucleic-acid-rich diets was due to increased ATP formation, enhanced electron transport chain activity, increased CoQ10 and cytochrome oxidase synthesis, and increased NADH oxidation.

Congestive Heart Failure (CHF)

Dr. Frank reported that nucleic acid supplementation resulted in the relief of shortness of breath and edema of the legs and ankles, and normalization of breathing sounds. Those who required three or more pillows to sleep were able to sleep on only one or two pillows. Most patients were able to reduce their dependence on digitalis and other drugs. Doses of RNA in excess of 2 grams daily were generally required to bring about these changes, though in one case he reported that an elderly patient required 9 grams of RNA daily.

At this dosage, Dr. Frank urged the patient to maintain an alkaline urine pH of 7.5, and to consume 400 mg of magnesium per day to prevent calcium kidney stone formation.

Emphysema and Obstructive Lung Disease

Dr. Frank reported that the marked oxygen-sparing (anti-anoxia) effects of nucleic acids played a very important role in the therapy of this crippling disease. In severe cases of emphysema, doses of RNA up to 15 grams three times per week were used. Dr. Frank noted that such high dosages of RNA often made the patient quite comfortable and greatly alleviated the feeling of breathlessness. He claimed that after several weeks on this regimen, bronchodilators could often be reduced or eliminated, and that once the antianoxia effect had been established, the dosage of RNA could be reduced to a maintenance dose of roughly half the initial dose required.

Dr. Frank believed the two actions of high-dose RNA—i.e., its mucolytic and antianoxia effects—might also be useful in the treatment of other pulmonary diseases, such as asthma and cystic fibrosis.

Diabetes

The major problem facing diabetics is that the disorder greatly accelerates virtually all of the diseases of aging, leading to serious complications of retinopathy, neuropathy, and nephropathy. The peripheral neuropathy often seen in diabetics results in severe pains, loss of vibratory sensation and touch, as well as disturbances in the motor nerves and autonomic nervous system. Dr. Frank was himself a very brittle, severe type 1 (insulin-dependent) diabetic. To control diabetes Dr. Frank recommended a standard therapy of diet, exercise, insulin, and oral hypoglycemics. He was also aware of the use of biguanides (the class of drugs to which Metformin belongs)—specifically, Phenformin (which was available in the U.S. until the late 1970s).

While Dr. Frank believed that RNA therapy could potentially benefit diabetic patients, he was concerned about using nucleic acids in severe cases that involved kidney dysfunction. This concern may explain Dr. Frank’s premature death, as his diabetes-induced nephropathy limited the dosage of RNA that he otherwise would have been able to tolerate (and which would probably have improved his diabetes-related symptoms).

Hypothyroidism

Dr. Frank recognized the high prevalence of thyroid disease in the elderly, and considered that this might be due to a chronic deficiency of dietary RNA. It is well known that the metabolic rate (and body energy production) declines with aging.

Many symptoms of hypothyroidism are consistent with age-related changes. RNA therapy causes a rise in body heat production (and presumably, the metabolic rate), and Dr. Frank attributed this to a normalization of thyroid function by RNA.

Resistance to Fatigue and Anti-Anoxia Effects

Dr. Frank conducted a number of animal experiments to evaluate the oxygen-sparing effect of nucleic acids. In one simple experiment, he placed mice in sealed jars to determine if RNA would affect the length of their survival. He found that RNA-fed experimental animals survived 48 percent longer than those on the control diet. In another experiment, he placed control and RNA-fed rats in a water tank to evaluate their swimming endurance. The RNA-fed rats averaged 15.6 minutes before sinking, versus 11.3 minutes for the control group. In other experiments, he demonstrated that nucleic acids enabled animals to perform more work using less oxygen than control animals, and to survive cold temperatures longer.

To his surprise, Dr. Frank found that the anti-anoxia effect of RNA was long lasting, in that the effect persisted for weeks after cessation of nucleic acid therapy. He believed that these long-lasting effects were due to enhanced CoQ10 synthesis, which helped maximize the energy production in the electron transport chain, resulting in more efficient oxygen utilization, greater energy formation, and more efficient ATP synthesis. He even speculated that it might be due to an increase in the number (as well as the efficiency) of the energy-producing mitochondria.

Dr. Frank believed that this anti-anoxia effect had profound anti-aging effects. He theorized that with increased nucleic acid intake, less oxygen was needed for a given amount of work, resulting in decreased oxidative damage. Thus, he believed that in addition to their other roles in aging and metabolism, nucleic acids were also very potent antioxidants. Nucleic acids clearly energize people-not the way drugs do, but by enhancing normal energy metabolism.

In addition to alleviation of chronic fatigue, Dr. Frank reported that RNA supplementation resulted in increased exercise tolerance and muscular strength, improvements in EKGs, normalization of liver enzymes, and increased mental acuity.

Dr. Frank stated that in most of his patients suffering from fatigue or low- level vitality, as soon as even 100 mg of nucleic acid were taken daily for a week or two, the patients felt noticeably better, although he conceded that these effects occurred more rapidly when higher doses were taken. With higher doses, he reported that these effects were seen as early as the second or third day. In some cases of chronic fatigue, he used dosages in the range of 5 to 20 gm of RNA three to five times weekly.

Retinitis Pigmentosa (RP) and Glaucoma

Retinitis pigmentosa (RP), though rare, is a significant cause of blindness. No treatment has been consistently successful in this disease. Dr. Frank reported a 35-year-old male with RP who achieved normal vision after one month of RNA therapy, consisting of five grams of RNA per day plus a serving of fish for lunch. Despite the improvement in vision, however, no retinal changes were observed.

Dr. Frank also treated three cases of glaucoma with this regimen, in which the patients were able to discontinue their medication (pilocarpine).

Narcotics and Alcohol Addiction

Dr. Frank treated a number of patients suffering from heroin or alcohol addiction.

For alcoholics, he used 7-15 grams, twice weekly. He reported that they generally showed improvements in strength, well-being, and facial skin color. Tremors decreased markedly, and mental clarity was much improved.

In several heroin addicts, he prescribed 2-5 grams of RNA three to five times weekly. The response was dramatic. The weakness and general haggard appearance became more normal, and the facial skin showed a ruddier complexion. Skin infections decreased, vitality returned, and the patients expressed an increased feeling of well-being.

Cancer

Cancer is the number two killer in the U.S., ranking behind only cardiovascular disease. Cancer cells are known to have a generally lower level of energy than normal cells, and to have a predominantly anaerobic metabolism. Enhancing the efficiency of oxidative phosphorylation and the citric acid (Krebs) cycle were of capital importance in Dr. Frank’s approach to treating and preventing cancer. Dr. Frank claimed that formulations which promote significant Krebs cycle metabolism in tumors (and the host) cause tumor regression. In addition to RNA, Dr. Frank found that histidine and carnosine were very potent anti-tumor compounds.

Dietary Sources of RNA

Foods rich in RNA include seafood (especially sardines), fish, beans, mushrooms, beef broth and vegetable soups. Nucleic acids can also be obtained from fish and nuts, as well as from many health foods. For dietary nucleic acids, Dr. Frank preferred sardines, claiming that therapeutic effects could be obtained by consuming one or two cans of sardines each day. Sardines contain 1.5 percent nucleic acids, whereas red meat (muscle) contains a paltry 0.05 percent.

Nucleic Acid Therapy-Dosage and Cautions

Dr. Frank recommended dosages of RNA across a wide range, starting at several hundred milligrams every day, and going up to 20 grams, taken three times per week. Dr. Frank’s dosages varied with individual tolerance, based on serum uric acid and BUN (blood urea nitrogen, a test of kidney function), as well as the clinical needs of the patient.

Although other scientists have found virtually no side effects from taking doses of 5 to 15 grams of RNA daily over prolonged periods of time, Dr. Frank erred on the side of caution, recommending dosages of 1.5 grams per day for the large majority of adults, and offering several precautions for those taking higher amounts.

Dr. Frank always recommended that a high-potency multinutrient formula be taken along with RNA, with a special emphasis on B complex vitamins and magnesium (400-500 mg per day). He also recommended drinking copious amounts of fluids (up to 8-10 glasses per day) when higher doses (more than 5 gm) of RNA were taken.

Contraindications and Side Effects

Dr. Frank believed that gout, high serum uric acids, and impaired kidney function were relative contraindications to high-dose RNA supplementation (more than 5 grams per day). He warned that high-dose oral RNA may cause uric acid deposition in the kidneys, leading to kidney stones.

He recommended that fasting blood uric acid level be determined prior to initiating high-dose therapy. He stated that those with uric acid of 2 or 3 mg could take much larger amounts of nucleic acid than those with levels of 5-7 mg. If BUN levels rose more than 5 mg% after initiation of therapy, he recommended that RNA intake be stopped for one to two weeks, fluid intake increased, and urine pH maintained above 7.5.

Dr. Frank also recommended maintaining urine pH in the alkaline range (i.e., 7.0 or above); pH is an indicator of the acidity/alkalinity of the urine. A neutral pH is 7.0, less than 7 is acid and greater than 7 is alkaline. Urine pH can be monitored using Nitrazine pH paper. If necessary, an alkalinizing agent like Alka Seltzer can be used two or three times per day to maintain pH in the alkaline range.

I think that Dr. Frank’s cautions are overly conservative, and that the large majority of people will not have any problems with increased dietary nucleic acid intake.

Conclusion

Despite Dr. Frank’s all-over-the-ballpark range of dosage recommendations, I believe that a reasonable dosage is a minimum of 1.5 gm per day for basic supplementation and preventive purposes, and that higher doses (5-15 gm per day) can be taken for therapeutic/anti-aging purposes.

Generally, younger people tolerate larger amounts than older people, although paradoxically, it is older people who need the highest dosages. Although Dr. Frank’s cautions listed above should be kept in mind, I believe he greatly overestimated the potential for adverse effects, because of his own diabetes-induced impaired kidney function (which may have restricted the amount of RNA he was able to consume).

Those with normal kidney function can take higher doses of RNA without problems. This is exemplified by the fact that the two teams of researchers described in the article about RNA in the October 2003 issue of Vitamin Research News took dosages of RNA of 5 to 15 gm per day for prolonged periods-without following Dr. Frank’s cautions-and without any adverse side effects reported.

Furthermore, the experimental animals took a human equivalent dose of 50 gm per day(!), without side effects, other than improved health and extended lifespans (Fig. 2).

In the 25 years of follow-up of Dr. Frank’s patients, his associate, Carmen Fusco, RN, reported that she has not observed a single case of RNA-induced kidney problems. Dr. Frank summed up his general recommendations for RNA supplementation:

• Administer RNA with a multinutrient formula (especially, high dose B complex) and 400-500 mg of magnesium
• Drink at least 8-10 glasses of fluid
• Watch urine pH-maintain in the range of 6.0-7.5.

I think RNA is one of the most under-utilized and most cost-effective anti-aging supplements there is, and should be an integral part of a comprehensive anti-aging regimen.

The Lasting Legacy of Dr. Benjamin Frank

Dr. Frank believed that because of the very pronounced anti-aging effect seen with increased nucleic acid relative to his own intake, he could live considerably longer, perhaps to near 150 years of age. He admitted that he had done no studies in humans of intakes of very large amounts of nucleic acids for prolonged periods of time.

It is apparent that aging itself is now a treatable disease. These results help ensure that a lifespan of more than a few centuries will before too long become a potential reality. — Benjamin S. Frank, M.D., November 1, 1978

Ironically, in less than a year after making this bold prediction, Dr. Frank had passed away at the age of 57-a victim of type 1 diabetes, a severe, age-accelerating disease which he had battled since childhood. It is a testimony to Dr. Frank’s brilliance that he survived as long as he did, suffering from as severe a case of diabetes as he had.

References:

1. Dean, W. A highly effective anti-aging supplement-Ribonucleic Acid. Vitamin Research News, 2003, 17: 10, 1-4, 11.

2. Dean, W. Review of potential anti-aging effects of Ribonucleic Acid. Vitamin Research News, 2003, 17: 1-3, 14.

3. Frank, B. Nucleic Acid Therapy in Aging and Degenerative Disease-A Metabolic Approach with DNA, RNA and Related Metabolites. Psychological Library, New York, 1968.

4. Frank, B. Dr. Frank’s No Aging Diet. The Dial Press, New York, 1976.

5. Frank, B. Nucleic Acid and Anti Oxidant Therapy of Aging and Degeneration, Royal Health Books, Ltd., Long Island, NY, 1977.

6. Robertson, T. On the influence of nucleic acids of various origins upon the growth and longevity of the white mouse. Australian J Exp Biol Med Sci, 1928, 5: 47-67.