• The President’s Desk  — When is a Vitamin Not a Vitamin?

• Iodine Deficiency  — An Under-Recognized Epidemic

• Can Common Blood Pressure Medications Cause Diabetes?  — 

• Skin Repair  — Stopping the Loss of Elasticity and a Common Cause of Wrinkles

• Depression and Bone Loss  — The Critical Link Between Two Common Disorders

• Pet Corner  — Osteoarthritis in Pets

• CDP Choline  — Powerful Cognitive-Enhancing Nutrient

• Nutrition Review  — Latest Research on Fatigue, Heart Health, Cognitive Enhancement and More

• Phlebitis
• Candida and Heavy Metals
• Torn Meniscus
• Seborrheic Dermatitis
• Bronchitis, Sinusitis
• Juvenile Rheumatoid Arthritis
• Carpal Tunnel Syndrome
• Mito-Boost®
• Chronic Cough
• Losing Height
• Infertility
• Weight Gain
• Joint Health, Weight Loss

The Food and Drug Administration (FDA)—apparently on a mission to limit consumer choice in the field of dietary supplements—recently released a ruling that sets a precedent that could ultimately lead to consumers being forced to obtain many natural products exclusively by prescription.

The FDA ruling involved pyridoxamine dihydrochloride, one of the three primary natural forms of vitamin B6, and was in response to a petition from Biostratum, the manufacturer of a pyridoxamine-based drug. The FDA verdict declared that pyridoxamine was authorized for investigation as a new drug before it was ever marketed as a dietary supplement and therefore cannot be sold as a dietary supplement. The ruling refers to a grandfathering clause that states that at the time a drug company files a new drug application for an ingredient, if that ingredient is already marketed as a nutritional supplement it can be sold simultaneously as both a supplement and a drug. Supplement companies must provide proof to substantiate that the ingredient was marketed and sold prior to the new drug application, otherwise the ingredient cannot be sold as a dietary supplement.

Pyridoxamine is a potent AGE-blocker and we knew it could help a lot of our customers. Yet, threatened with legal action, we were forced to remove it from our Benfotiamine/Pyridoxamine formula several years ago.

This policy of blocking access to beneficial natural substances is not designed to protect the consumer. Rather, it’s to protect drug companies’ profits.

The pyridoxamine issue will likely prove to be just the tip of the iceberg. Recently, there was the first hint that DMSA may also be outlawed as a dietary supplement for the same reasons.

If this continues, advances in nutritional science may go through the more profitable drug-filing route (and by regulation avoid the dietary supplement market rather than including the dietary supplement market) thereby depriving US consumers of immediate availability and affordability. The bottom line: good for drug companies, bad for consumers.

I have been involved in the iodine project for seven years. During this time, iodine has consistently provided the most satisfying clinical results as compared to any other nutrient. To date, my partners and I have tested nearly 5,000 patients for iodine levels. Our results show that more than 96 percent of patients tested have low iodine levels with the vast majority being severely iodine deficient. I believe iodine deficiency is occurring at an epidemic rate across the United States. The consequences of iodine deficiency are severe: mental retardation, lowered IQ, attention deficit hyperactivity disorder (ADHD), infertility, thyroid problems, and cancer of the breast, prostate, ovaries, thyroid and uterus.

Unfortunately, a lot of misinformation exists about iodine. People are afraid to use iodine because of unsubstantiated rumors about this nutrient. This article, excerpted in part from my book, Iodine Why You Need It, Why You Can’t Live Without It, is written to provide the reader with the correct information about iodine so that the reader can make an educated decision about whether to supplement with this important nutrient.

For more than 100 years, iodine has been known as the element that is necessary for thyroid hormone production. However, it is rare to see any further mention of iodine’s other effects. Iodine is found in each of the trillions of cells in the body. Without adequate iodine levels, life itself is not possible.

Iodine is not only necessary for the production of thyroid hormone, it is also responsible for the production of all of the other hormones of the body. Adequate iodine levels are necessary for proper immune system function. Iodine contains potent antibacterial, antiparasitic, antiviral, and anticancer properties. Iodine is also effective for treating fibrocystic breasts and ovarian cysts. Table 1 lists some of the many benefits of iodine and some of the conditions that would benefit from adequate iodine supplementation.

Approximately 1.5 billion people, about one-third of the earth’s population, live in an area of iodine deficiency as defined by the World Health Organization. Iodine deficiency disorder can result in mental retardation, goiter, increased child and infant mortality, infertility, and socioeconomic decline.¹ Iodine deficiency disorder is the most common preventable form of mental retardation known.

Iodine is a relatively rare element, ranking 62^nd in abundance of the elements of the earth. Iodine is primarily found in seawater in very small quantities and solid rocks (usually near the ocean) that form when seawater evaporates. Iodine can also be found in sea organisms, such as seaweed. In fact, seaweed is one of the most abundant sources of iodine because seaweed has the ability to concentrate a large amount of iodine from the ocean water.

Iodine is not very abundant in the earth’s crust.² It is estimated to be about 0.3-0.5 parts per million. In fact, it is in the bottom third of the elements in terms of abundance.²

If the soil has adequate iodine levels, the crops grown on that soil will contain adequate iodine levels. Conversely, deficient iodine levels will be found in crops grown on iodine-deficient soil.

There are naturally occurring non-radioactive and radioactive forms of iodine. Radioactive iodine can be used in medicine to diagnose and treat certain illnesses, particularly illnesses of the thyroid gland.

Commercially available non-radioactive iodine primarily comes from several sources: Chilean Saltpeter, seaweed, and brine water in oil wells. The action of the waves from the ocean can make iodine gas. Once airborne, iodine can combine with water or air and enter the soil. Non-radioactive iodine can enter our food system in a variety of ways. First, plants can take up iodine from the soil. Second, airborne iodine can land on fresh water supplies and, finally, airborne iodine can land on the ground, combine with salt, and become iodized salt.

Radioactive iodine can enter the air from reactions in nuclear power plants or explosions of nuclear materials. Radioactive iodine has been associated with certain types of cancer including thyroid cancer and certain blood cancers. Children are more susceptible to radioactive iodine since they have smaller thyroid glands, and they will receive a proportionately larger radioactive dose than an adult when they are exposed to radioactive iodine. Radioactive iodine damage can be prevented by the ingestion of non-radioactive inorganic iodine.

Where Is Iodine Found in the Body?

Every cell in the body contains and utilizes iodine, but iodine is concentrated in the glandular system of the body. The thyroid gland contains a higher concentration of iodine than any other organ. Large amounts of iodine are also stored in many other areas including the salivary glands, cerebrospinal fluid and the brain,³ gastric mucosa, choroid plexus, breasts, ovaries, and the ciliary body of the eye. In the brain, iodine concentrates in the substantia nigra, an area of the brain that has been associated with Parkinson’s disease. Iodine is essential for the normal growth and development of children. Severe iodine deficiency can result in severe mental deficiency and deafness (i.e., cretinism). In addition, spontaneous abortion, as well as delayed physical and intellectual development is associated with iodine deficiency. Attention deficit/hyperactivity disorder (ADHD) is also related to iodine deficiency (see chapter 10 of my book).

Conversely, too much iodine can be a problem. In rare cases, excess iodine (i.e., doses greater than 1 gram/day) has been associated with hyperthyroid symptoms.

How Much Iodine Do You Need?

Now that you can see the body’s needs for iodine and what happens when iodine is deficient, the next logical question is, “How much iodine do I need to take?”

The best way to ascertain how much iodine you need to take is to figure out the body’s iodine status. Iodine levels can be checked in the blood, serum or urine. The most accepted test is the urinary test. I believe the best test to measure iodine levels is the iodine loading test.

My mentor on iodine, Dr. Guy Abraham, developed the iodine loading test. This test can be ordered here. It is done by ingesting 50 mg of iodine and collecting 24 hours of urine. By measuring the amount of iodine excreted in the urine, you can ascertain the iodine status of the body. Our research has shown that healthy people have approximately a 90 percent excretion. Therefore, if they ingested 50 mg of iodine in 24 hours they will excrete approximately 45 mg and retain 5 mg. The more ill one is, generally the lower the excretion rate. In essence, if one is very ill, their body will be calling for more iodine and they will excrete less during the loading test. In this case, they will retain a large portion of the loading test and their excretion rate will be lower than 90 percent.

Having an iodine loading test performed can help guide you in the proper dosing of iodine. My experience has shown that most adults will do well taking iodine in the range of 25-50 mg/day. Children need lower doses and can be dosed appropriately based on their size. My experience has shown that a healthy individual taking 50 mg of iodine/day will achieve iodine sufficiency in approximately 6 months.

However, 50 mg/day of iodine in an individual ill with a serious illness such as cancer or an autoimmune disorder may be insufficient to meet their needs. My clinical and laboratory experience has shown that ill individuals generally need more iodine as compared to healthy individuals. At 25-50 mg/day of iodine, it may take years for an ill individual to become iodine sufficient. In these cases, I sometimes recommend increased dosages of iodine. I do not recommend anyone dose iodine on their own. The best results are found when working with a holistic health provider who is knowledgeable about iodine. Furthermore, the best results are found by using iodine as part of a comprehensive holistic regimen that includes balancing vitamins, minerals, and hormones.

When undertaking an iodine supplementation program, it is important to use iodine from a reputable company. A reputable company should be able to verify the contents of its products. Iodoral^® is one such product that has been properly studied and verified. Iodoral is a tableted iodine product. Its use has stood the test of time. I have been using Iodoral in my practice for more than seven years and found consistently positive results with it.

Final Thoughts

There is so much misinformation about iodine. It is important for you, the reader, to do your own research and come up with your own conclusions about iodine. Once you understand the importance of this vital element, you will understand why it is crucial to ensure adequate iodine levels in you and your family.

Iodine deficiency is occurring at epidemic rates. I have no doubt that this deficiency is responsible (at least in-part) for the epidemic of cancers of the breast and prostate as well as thyroid disorders. My clinical experience has clearly shown that it is impossible to treat these disorders as well as other chronic illnesses such as autoimmune diseases without ensuring adequate iodine intake.

Remember, the best results are achieved when working with a skilled health care practitioner who is knowledgeable about iodine. More information about iodine can be found in my book, Iodine Why You Need It, Why You Can’t Live Without It, available here.

References

1. Manner, M.G., et al. Salt Iodization for the Elimination of Iodine Deficiency. International Council for the Control of Iodine Deficiency Disorders. 1995.

2. Modern Nutrition in Health and Disease, 9th Edition. Williams and Wilkins, 1999.

3. Adrasi, E. Iodine concentration in different human brain parts. Analytical and Bioanalytical chemistry. November 13, 2003.

High blood pressure, or hypertension, is a major risk factor for cardiovascular disease. In the United States, approximately one in three adults has high blood pressure, totaling an estimated 72 million people. Additionally, more than half of Americans over the age of 60 have hypertension.¹

High blood pressure can be caused by a number of factors including hormones, kidney disease, and cardiovascular disorders. Blood pressure increases due to increased force of the contraction of the heart and increased peripheral resistance in the blood vessels. As was mentioned in the previous issue of Vitamin Research News, in the renin-angiotensin system, the enzyme renin activates the hormone angiotensin-1, which is then converted to angiotensin-2 by angiotensin-converting enzyme (ACE). Angiotensin-2 increases blood pressure by increasing sodium and water retention from the kidneys and constricting the smooth muscle around the arteries. Additionally, nitric oxide is a molecule that is produced in the endothelial lining of blood vessels where it locally causes the smooth muscle surrounding the blood vessels to relax. Sufficient production of nitric oxide is required to decrease peripheral resistance of the blood vessels. Peripheral resistance can also be increased as a result of hardening of the arteries due to calcium deposits and atherosclerotic plaque formation. There is also research regarding parathyroid hypertensive factor (PHF), a substance released from the parathyroid gland that is believed to increase blood pressure by interfering with normal calcium channel activity in vascular smooth muscle cells. Elevated PHF levels correlate with hypertension, especially in low-renin, salt-sensitive patients.^2-4

There are several types of pharmaceuticals commonly prescribed to manage high blood pressure, in addition to diet and lifestyle modifications. Diuretics, or water pills, are used to flush excess fluid and sodium from the body to decrease the amount of fluid pumped by the heart. Beta-blockers are used to decrease the rate and force in which the heart pumps blood, and alpha-blockers decrease nerve impulses that constrict blood vessels. Calcium channel blockers inhibit calcium from entering the muscle cells of the heart and blood vessels, allowing blood vessels to relax. Angiotensin converting enzyme (ACE) inhibitors suppress the hormone angiotensin-2, which causes water retention and blood vessels to narrow.⁵

It is interesting that death caused by coronary artery disease and sudden death is not significantly reduced by the use of anti-hypertensive medications in hypertensive patients, despite the evidence that hypertension is a major risk factor for heart attacks.⁶ Some researchers suggest that this is due to adverse metabolic effects caused by the pharmaceuticals that counteract the benefits of lower blood pressure.⁶ For example, diuretics disrupt electrolytes causing low potassium, magnesium, and sodium, and may increase uric acid. Thiazide diuretics are also associated with a decline in kidney function.⁷ Both diuretics and beta-blockers interfere with blood glucose and lipid metabolism, and ACE inhibitors can elevate potassium.⁸

Some of the most concerning findings indicate that thiazide diuretics, considered the first-choice drug for hypertension, are associated with an increased risk of diabetes. In one study, non-diabetic subjects age 60 or older with systolic hypertension were treated with the thiazide diuretic chlorthalidone or a placebo. The results showed that this diuretic significantly decreased levels of serum potassium, known as hypokalemia, and this correlated with a significant increase in diabetes. In fact, the study showed that for each 0.5 milliequivalent-per-liter (MEq/L) decrease in serum potassium, there was a 45 percent increased risk of developing diabetes.⁹ Diabetes mellitus and hypertension each independently confer increased cardiovascular risk, and that risk is much greater when the diseases coexist.

According to the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, thiazide-type diuretics should be used as the first choice therapy for most patients with hypertension, despite the data from the large ALLHAT trial, which showed that thiazide-type diuretics cause hypokalemia, glucose intolerance, and diabetes. The study showed a significant 43-65 percent higher risk of new-onset diabetes with the diuretic chlorthalidone compared with a calcium channel blocker (30 percent) and an ACE inhibitor (18 percent). The researchers justified their recommendation to use thiazide-type diuretics as the first choice therapy for most patients with hypertension based on the data that the greater incidence of diabetes did not translate into more cardiovascular events. However, other researchers suggest that drawing such a conclusion ignores the morbidity and mortality associated with diabetes over decades, and not the short 2-6 year time frame examined in the ALLHAT study.^10-11

Another study found a similar association between anti-hypertensive drugs and diabetes. This long-term study found that 20.4 percent of hypertensive subjects treated with anti-hypertensive medications developed diabetes, and new-onset diabetes correlated with a significantly increased risk for stroke, myocardial infarction, and mortality.¹² Other studies have shown that the mean fasting glucose levels increased with thiazide-type diuretics, a calcium-channel blocker, or ACE inhibitor measured after 4.9 years,¹³ and patients with hypertension who were taking beta-blockers had a 28 percent higher risk of developing type 2 diabetes.¹⁴

In addition to diabetes, anti-hypertensive medications are associated with adversely impacting lipid profiles. Studies have shown that beta-blockers reduced the ratio of beneficial high-density lipoprotein (HDL) to total cholesterol by 11.7 percent and increased serum triglyceride levels by 25.8 percent.¹⁵ Diuretics can cause an increase in total and low-density lipoprotein (LDL) cholesterol and triglyceride levels while beta-blockers can decrease HDL cholesterol and increase triglyceride levels.¹⁶ Some beta-blockers also have been found to decrease levels of CoQ10.¹⁷

Natural Support for High Blood Pressure

Hypertension can have dangerous consequences and patients should never stop taking their blood-pressure lowering drugs without a doctor’s guidance. However, for individuals who want to explore other options, there are a number of approaches that can be taken.

Natural products have many different mechanisms to modulate blood pressure. Cordyceps and shark cartilage, as found in PRESSURE-fX™, address both the renin-angiotensin system as well as PHF. Research suggests that shark cartilage and Cordyceps are PHF antagonists. Animal models show that shark cartilage administration decreased blood pressure and modulates intracellular calcium regulation.¹⁸ Studies indicate that Cordyceps also lowers blood pressure in animal models, relaxes blood vessels, and elicits a dose-dependent relaxation of extra-cellular calcium-dependent contractions.¹⁹ Researchers believe that shark cartilage and Cordyceps may benefit both high-renin and high-PHF patients. A clinical trial with hypertensive patients showed that adding PRESSURE-fX was more effective at lowering blood pressure than diet, lifestyle modifications, and mineral supplementation alone. In fact, 88 percent of subjects had significantly reduced blood pressure, and 75 percent of subjects were able to maintain normal blood pressure without medication.²⁰

While a blend of Cordyceps and shark cartilage can be used in patients whose blood pressure issues are caused by an increase in intracellular calcium, a combination of grape seed extract, a special form of blueberry extract and vitamin K2 (as in Circutrol BP™) can often be useful in patients who are deficient in nitric oxide and who experience increased ACE activity and arterial calcification. Grape seed extract has been shown to increase platelet-derived nitric oxide production, which induces relaxation of blood vessels.^21-22 Additionally, animal models suggest that grape seed extract acts as a calcium channel blocker.²³ One clinical trial showed that 300 mg per day of grape seed extract supplemented for 8 weeks decreased systolic blood pressure by an average of 8.3 mmHg and diastolic blood pressure by 5.7 mmHg.²⁴

Research also suggests that blueberry extract acts as a potent ACE inhibitor. In one study, a diet containing 3 percent blueberry extract or a control diet was fed to spontaneously hypertensive stroke-prone rats for 8 weeks. The blood pressure of the spontaneously hypertensive stroke-prone rats was 30 percent lower on the blueberry diet than on control diet at 6 weeks. In addition, the rats on the blueberry diet showed a 48 percent lower glucose/insulin ratio compared to rats on the control diet. The researchers concluded that a 3 percent blueberry diet can delay the onset and reduce the magnitude of hypertension, and may reduce insulin resistance in these rats.²⁵ Another study fed rats a diet supplemented with blueberries and showed that the blueberry diet affects vascular smooth muscle contraction by suppressing a1-adrenergic receptor agonist-mediated contraction.²⁶

Vitamin K2 (menaquinone) can also be an important part of a blood-pressure-maintenance formula. Vitamin K2 promotes arterial elasticity by inhibiting calcification of blood vessel walls. Vitamin K is a cofactor for the Matrix Gla-Protein found in blood vessel walls that functions to inhibit vascular calcification and atherosclerosis.²⁷ Researchers have demonstrated in human studies that increased intake of vitamin K2 is associated with decreased coronary calcification.²⁸

Conclusion

Research is beginning to indicate that certain prescription anti-hypertensive agents may be associated with an increased risk of diabetes. Both Cordyceps and shark cartilage, found in PRESSURE-fX, and grape seed extract, blueberry extract, and vitamin K2, found in Circutrol BP, can help to maintain healthy blood pressure levels. Each formula has unique mechanisms to address the numerous potential causes of high blood pressure.

References

1. National Institutes of Health. Who is at Risk for High Blood Pressure? Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/Hbp/HBP_WhoIsAtRisk.html. Accessed on: 02-07-09.

2. Pang PK, Benishin CG, Shan J, et al. PHF: the new parathyroid hypertensive factor. Blood Press. 1994 May;3(3):148-55.

3. Lewanczuk RZ, Resnick LM, Blumenfeld JD, et al. A new circulating hypertensive factor in the plasma of essential hypertensive subjects. J Hypertens. 1990;8:105-108.

4. Pang PK, Benishin CG, Shan J, et al. Parathyroid Hypertensive Factor: A new vasoactive substance from the parathyroid gland. In “Calcium Regulating Hormones and Cardiovascular Function,” MF Crass and LV Avioloi (eds.), CRC Press Inc., Boca Raton, Florida, 111-130, 1995.

5. National Institutes of Health. How is High Blood Pressure Treated? Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/Hbp/HBP_Treatments.html. Accessed on: 02-07-09.

6. Morgan TO. Metabolic effects of various antihypertensive agents. J Cardiovasc Pharmacol. 1990;15 Suppl 5:S39-45.

7. Reungjui S, Pratipanawatr T, Johnson RJ, et al. Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia. Curr Opin Nephrol Hypertens. 2008 Sep;17(5):470-6.

8. Preuss HG, Burris JF. Adverse metabolic effects of antihypertensive drugs. Implications for treatment. Drug Saf. 1996 Jun;14(6):355-64.

9. Shafi T, Appel LJ, Miller ER 3rd, et al. Changes in serum potassium mediate thiazide-induced diabetes. Hypertension. 2008 Dec;52(6):1022-9.

10. Punzi HA, Punzi CF; Antihypertensive and Lipid-Lowering Heart Attack Trial Study; Trinity Hypertension Research Institute. Metabolic issues in the Antihypertensive and Lipid-Lowering Heart Attack Trial Study. Curr Hypertens Rep. 2004 Apr;6(2):106-10.

11. Aksnes TA, Reims HM, Kjeldsen SE, et al. Antihypertensive treatment and new-onset diabetes mellitus. Curr Hypertens. Rep 2005 Aug;7(4):298-303.

12. Almgren T, Wilhelmsen L, Samuelsson O, et al. Diabetes in treated hypertension is common and carries a high cardiovascular risk: results from a 28-year follow-up. J Hypertens. 2007 Jun;25(6):1311-7.

13. Barzilay JI, Davis BR, Cutler JA, et al. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2006 Nov 13;166(20):2191-201.

14. Gress TW, Nieto FJ, Shahar E, et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med. 2000 Mar 30;342(13):905-12.

15. Leren P. Comparison of effects on lipid metabolism of antihypertensive drugs with alpha- and beta-adrenergic antagonist properties. Am J Med. 1987 Jan 5;82(1A):31-5.

16. Hunninghake DB. Effects of celiprolol and other antihypertensive agents on serum lipids and lipoproteins. Am Heart J. 1991 Feb;121(2 Pt 2):696-701.

17. Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977 May;17(1):157-64.

18. Communication with Peter Pang, Ph.D., professor emeritus, University of Alberta, December 2001.

19. Pang PK, Shan JJ, Chiu KW. The Cardiovascular Effects of Cordyceps Sinensis in Normotensive Rats. Journal of Chinese Medicine. 1996; 7(2):153-167.

20. Malina O, Malina M, Kotsifas G, et al. Treatment of Mild to Moderate Arterial Hypertension with Pressure-FX®. Unpublished research. Instituto de Medicina Ortomolecular, Parana, Brazil.

21. 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.

22. Freedman JE, Parker C, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001;103:2792-8.

23. Zhang TX, Niu CQ, Hu JM, et al. 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.

24. Lu B, Robinson M, Kappagoda T. Effect of a Novel Grape Seed Extract on Blood Pressure in Subjects with Prehypertension. Presented at the FASEB Experimental Biology Conference, Washington, DC, April 30, 2007.

25. Sweeney M, Shaughnessy K, Gottschall-Pass K. Blueberry diets delay the onset of hypertension and reduce insulin resistance in spontaneously hypertensive stroke prone rats. FASEB J. 2007;21:847.

26. Norton C, Kalea AZ, Harris PD, et al. Wild Blueberry-Rich Diets Affect the Contractile Machinery of the Vascular Smooth Muscle in the Sprague–Dawley Rat. J Med Food. 2005 Spring;8(1):8-13.

27. Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603.

28. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2008 Jul 19. Published online ahead of print.

Scientists have long known that sugar affects how the body ages, based on observations of diabetics, who age rapidly.¹ Sugars are essential for energy, but once in the circulation they can also attach themselves to the amino groups of tissue proteins, cross-linking them into stiff, inflexible compounds known as advanced glycation end products, or AGEs. In fact, the same browning reaction that occurs when meat is cooked at high heat without moisture takes place at a slower rate in long-lived proteins such as collagen when the body’s tissues and cells are exposed to high or even normal levels of sugar for a long enough time.^2-3

Structural proteins such as collagen form an integral part in maintaining the structure of our body’s largest organ—the skin. Because collagen accounts for up to a third of the body’s proteins and has a slow turnover rate,⁴ it is especially vulnerable to glycation, which causes healthy collagen strands to lose their elasticity and firmness,⁵ resulting in wrinkles, dryness, and sagging that are characteristic of aging.

During the normal course of aging, there is a five-fold increase in the concentration of various glycotoxins in the collagen of healthy people.³ AGEs that accumulate in dermal collagen and elastin tissues have been shown to interact with the cell membrane of major skin cells known as fibroblasts,⁶ distorting their structure and function. A specific receptor for AGEs (called RAGE) has even been found to be highly expressed in human fibroblasts, which further influences the process of skin aging.⁶

In vitro studies also reveal that young human epidermal skin cells age rapidly when exposed to glucose,⁷ while apoptosis (programmed cell death) of human fibroblasts rises when they are exposed to AGEs.⁸ Animal studies echo these findings: skin collagen has been shown to undergo extensive cross-linking and glycation as well as increased AGE formation when rats are fed a high-fructose diet.⁴ In addition, the effects of glycation are further exacerbated because AGEs can inflict direct cytotoxic damage to dermal cells by triggering inflammatory messengers such as nuclear factor kappa B (NFk-B) and activator protein-1 (AP-1), which can activate inflammatory cytokines such as tumor necrosis factor and interleukin-1.

There is also evidence that AGEs can decrease the synthesis of a natural moisturizing agent in the skin called hyaluronic acid.¹⁰ Our skin consists of the outer layer called the epidermis and the dermis below. New cells generated by the dermis are continually being pushed upwards to replace the epidermis. The dermis is the inner layer of skin that contains collagen, which makes up 70 percent of the dry weight of the dermis. By attracting water in the dermis, hyaluronic acid hydrates the collagen and facilitates moisture retention, which provides elasticity to prevent wrinkles. Youthful skin contains abundant levels of hyaluronic acid, but levels decline with aging.¹¹ The accelerated decline caused by AGEs further compromises skin integrity.¹⁰

The damage wrought by glycation does not stop there. As well as contributing to the progression of skin aging in healthy people, increased levels of AGEs also cause premature aging and poor wound healing in the skin of people with diabetes. A number of studies even show that the accumulation of specific AGE molecules in the skin provides an accurate indication not only of the level of glycation in the rest of the body but also of the progression of diabetic complications.^12-13

Sugar and the Skin

The past few decades have seen an alarming increase in the dietary intake of sugar in the form of fructose from the ubiquitous high-fructose corn syrup that is used as an additive in many processed foods such as soft drinks, breakfast cereals, and breads, to name but a few. Unfortunately, the rate of AGE formation on intracellular proteins occurs up to 10 times faster in the presence of fructose compared with glucose.² Ideally, it would be best to avoid foods that generate AGEs in order to preserve healthy skin, but that is not always possible for many of us in today’s world.

The success of long-term intensive glucose control in reducing skin glycation, glycoxidation, and cross-links in people with type 1 diabetes¹⁴ provides us with important clues for slowing down the rate at which skin ages. Not surprisingly, a number of the strategies targeted at reducing the production of AGEs and their devastating consequences can also be used in the battle against skin aging, as highlighted below.

Skin Health From the Inside Out

Consuming a formula that contains the AGE-inhibiting nutrients below (all found in AGEBlock^®) can help reduce the damaging process of glycation, thereby helping to produce glowing, healthy skin.

Lipoic acid: This powerful antioxidant protects against glycation, reducing AGE-induced cross-linking of collagen in the skin.⁴ It also increases the cell’s ability to use glucose, decreasing the amount of free glucose available to be glycated.⁴ In addition, lipoic acid effectively recycles vitamins C and E and glutathione, which further inhibit protein glycation and AGE formation.⁴ It also turns off the activation of NFk-B that can severely damage skin through inflammatory processes.¹⁵

Carnosine: This dipeptide comprising beta-alanine and histidine serves as an invaluable weapon by shielding the body’s proteins from degradation. Studies have shown that as well as effectively preventing healthy collagen from becoming glycated,¹⁶ carnosine facilitates the removal of proteins that have already become glycated.¹⁷ Researchers have also shown that it restores the body’s regenerative potential by rejuvenating aging human skin cells grown in culture with carnosine and extending their life span,¹⁸ while also showing promising results in wound healing.¹⁹

Histidine: Carnosine can be broken down to its primary functional amino acids, L-histidine and beta-alanine. Histidine effectively inhibits protein glycation in vivo,²⁰ playing a significant functional role within the carnosine molecule for optimum protection against protein cross-linking.²¹ The combination of histidine, beta-alanine, and carnosine has been shown to confer powerful long-term protection against aldehyde-mediated protein cross-linking and loss of enzyme activity.²⁰

N-Acetyl Cysteine: This well-known antioxidant has been shown to suppress the generation of a major glycotoxin called N-(epsilon)-(carboxymethyl)-lysine (CML), which is a sequential product of glycation and oxidation processes. In one study, NAC successfully inhibited the formation of CML in type 1 collagen proteins, the predominant form of collagen found in the skin, after incubation for 16 weeks with glucose.²² In addition, the duo of NAC and carnosine provides a potent combination for reducing AGE-induced cell death in skin cells.⁸

L-Arginine: This naturally occurring amino acid has a structure similar to that of the well-known anti-glycating agent aminoguanidine²³ and guards the body’s healthy proteins from being converted into AGEs. Arginine is also a building block of skin proteins such as collagen and elastin and has been shown to increase the amount of reparative collagen synthesized at the site of a wound in burn patients.²⁴

Vitamin B6: Pyridoxal-5-Phosphate (PLP or P5P), an active form of vitamin B6, significantly decreased the formation of AGEs, cross-linking of skin collagen, and the development of diabetic nephropathy in rats, leading scientists to conclude, “PLP is considered a promising active form of vitamin B6 for the treatment of AGE-linked disorders such as diabetic nephropathy.”²⁵

Vitamin B1 (thiamine) and Benfotiamine: As the highly bioavailable form of vitamin B1, benfotiamine works by blocking three of the major biochemical pathways through which high blood sugar levels inflict inflammatory damage on the cells.²⁶ It also enhances the activity of an enzyme called transketolase, which is essential for maintaining normal glucose pathways, and prevents the activation of the proinflammatory transcription factor NFk-B.²⁶

Yerba Mate: Abundant polyphenols found in extracts of this tea-like beverage consumed widely across South America have been shown to block glycation as effectively as the standard anti-glycation agent aminoguanidine.²⁷ Another rich source of polyphenolic content can be found in the aqueous extract of the Guava plant, which also has proved to be a strong inhibitor of protein glycation in human cells exposed to high glucose concentrations in vitro.²⁸

External Skin Protection

As mentioned above, AGEs can decrease the synthesis of a natural moisturizing agent in the skin called hyaluronic acid. While AGE-blocking nutrients can protect against the loss of elasticity that causes visible skin damage, this internal nourishment can be complemented with the topical use of hyaluronic acid. Replenishing the skin with hyaluronic acid provides essential moisture, counteracts the loss of skin volume and fullness that occurs with aging,^29-30 and increases cell renewal.³¹

Conclusion

Although collagen tends to cross-link naturally with age, the presence of high concentrations of glucose accelerates this process, robbing skin of youthful elasticity and tone. Reducing sugar levels in the body not only confers longer life, it also manifests in a reduced rate of skin aging. Fortunately, a range of novel AGE-blocking nutrients can rejuvenate skin by protecting against the stiff sugar-protein bonds that accumulate as we get older and can be complemented by the topical use of hyaluronic acid, which provides extra firming and hydration support.

References

1. Van Boekel MA. The role of glycation in aging and diabetes mellitus. Mol Biol Rep. 1991 May;15(2):57-64.

2. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006 Aug 8;114(6):597-605.

3. Dyer DG, Dunn JA, Thorpe SR, et al. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest. 1993 Jun;91(6):2463-2469.

4. Thirunavukkarasu V, Nandhini AT, Anuradha CV. Fructose diet-induced skin collagen abnormalities are prevented by lipoic acid. Exp Diabesity Res. 2004 Oct-Dec;5(4):237-244.

5. Pageon H, Técher MP, Asselineau D. Reconstructed skin modified by glycation of the dermal equivalent as a model for skin aging and its potential use to evaluate anti-glycation molecules. Exp Gerontol. 2008 Jun;43(6):584-588.

6. Lohwasser C, Neureiter D, Weigle B, Kirchner T, Schuppan D. The receptor for advanced glycation end products is highly expressed in the skin and upregulated by advanced glycation end products and tumor necrosis factor-alpha. J Invest Dermatol. 2006 Feb;126(2):291-299.

7. Berge U, Behrens J, Rattan SI. Sugar-induced premature aging and altered differentiation in human epidermal keratinocytes. Ann N Y Acad Sci. 2007 Apr;1100:524-9.

8. Peterszegi G, Molinari J, Ravelojaona V, Robert L. Effect of advanced glycation end-products on cell proliferation and cell death. Pathol Biol (Paris). 2006 Sep;54(7):396-404.

9. Alikhani M, Maclellan CM, Raptis M, Vora S, Trackman PC, Graves DT. Advanced glycation end products induce apoptosis in fibroblasts through activation of ROS, MAP kinases, and the FOXO1 transcription factor. Am J Physiol Cell Physiol. 2007 Feb;292(2):C850-C856.

10. Okano Y, Masaki H, Sakurai H. Dysfunction of dermal fibroblasts induced by advanced glycation end-products (AGEs) and the contribution of a nonspecific interaction with cell membrane and AGEs. J Dermatol Sci. 2002 Sep;29(3):171-180.

11. Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994;102:385-389.

12. Sell DR, Nagaraj RH, Grandhee SK, et al. Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging, and uremia. Diabetes Metab Rev. 1991 Dec;7(4):239-251.

13. Meerwaldt R, Links TP, Graaff R, et al. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy. Diabetologia. 2005 Aug;48(8):1637-1644.

14. Monnier VM, Bautista O, Kenny D, et al. Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial. Diabetes. 1999 Apr;48(4):870-880.

15. Saliou C, Kitazawa M, McLaughlin L, et al. Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line. Free Radic Biol Med. 1999 Jan;26(1-2):174-183.

16. Alhamdani MS, Al-Azzawie HF, Abbas FK. Decreased formation of advanced glycation end-products in peritoneal fluid by carnosine and related peptides. Perit Dial Int. 2007 Jan-Feb;27(1):86-89.

17. Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med. 2000 May 15;28(10):1564-1570.

18. Hipkiss AR, Brownson C, Bertani MF, Ruiz E, Ferro A. Reaction of carnosine with aged proteins: another protective process? Ann N Y Acad Sci. 2002 Apr;959:285-294.

19. Nagai K, Suda T, Kawasaki K, Mathuura S. Action of carnosine and beta-alanine on wound healing. Surgery. 1986 Nov;100(5):815-821.

20. Rashid I, van Reyk DM, Davies MJ. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett. 2007 Mar 6;581(5):1067-1070.

21. Hobart LJ, Seibel I, Yeargans GS, Seidler NW. Anti-crosslinking properties of carnosine: significance of histidine. Life Sci. 2004 Jul 30;75(11):1379-1389.

22. Nakayama M, Izumi G, Nemoto Y, et al. Suppression of N(epsilon)-(carboxymethyl)lysine generation by the antioxidant N-acetylcysteine. Perit Dial Int. 1999 May-Jun;19(3):207-210.

23. Servetnick DA, Bryant D, Wells-Knecht KJ, Wiesenfeld PL. L-Arginine inhibits in vitro nonenzymatic glycation and advanced glycosylated end product formation of human serum albumin. Amino Acids. 1996;11(1):69-81.

24. De-Souza DA, Greene LJ. Pharmacological nutrition after burn injury. J Nutr. 1998 May;128(5):797-803.

25. Nakamura S, Li H, Adijiang A, Pischetsrieder M, Niwa T. Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrol Dial Transplant. 2007 Aug;22(8):2165-74.

26. Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003 Mar;9(3):294-299.

27. Lunceford N, Gugliucci A. Ilex paraguariensis extracts inhibit AGE formation more efficiently than green tea. Fitoterapia. 2005 Jul;76(5):419-27.

28. Hsieh CL, Huang CN, Lin YC, Peng RY. Molecular action mechanism against apoptosis by aqueous extract from guava budding leaves elucidated with human umbilical vein endothelial cell (HUVEC) model. J Agric Food Chem. 2007 Oct 17;55(21):8523-8533.

29. Galus R, Antiszko M, Włodarski P. Clinical applications of hyaluronic acid. Pol Merkur Lekarski. 2006 May;20(119):606-608.

30. Carruthers J, Carruthers A. Hyaluronic acid gel in skin rejuvenation. J Drugs Dermatol. 2006 Nov-Dec;5(10):959-964.

31. Greco RM, Iocono JA, Ehrlich HP. Hyaluronic acid stimulates human fibroblast proliferation within a collagen matrix. J Cell Physiol. 1998 Dec;177(3):465-473.

Depression is a serious condition affecting more than 20 million Americans. Depressive disorders involve the mind, body, mood and cognition and can take many forms, such as major depressive disorder, bipolar disorder and dysthymia. At first glance, depression seems to have an effect exclusively on mental health. However, emerging research has established a link between this illness and osteoporosis, the most common degenerative disease in the developed world.

Both depression and osteoporosis impose a substantial public health problem, which is further magnified when both present in the same individual.

Evidence of a Link

Osteoporosis, an often-silent disease, is characterized by low bone mass, structural deterioration of bone tissue architecture, and increased risk of fractures. Low bone mineral density (BMD) and increased incidence of osteoporosis and fractures have been observed in patients with depressive disorders.^1-10

Dozens of studies have been conducted since the 1990s to examine the relationship between negative mood and reduced bone mass. Some of these include early clinical studies, in which patients with major depressive disorder exhibited approximately 6 to 15 percent lower BMD compared to controls.^4-5 In community-based studies, depression was associated with a 7.8 percent reduction in total hip BMD in peri­menopausal women (after adjusting for age, weight, and hormone therapy use);⁶ a 3.6 percent and 3.4 percent lower BMD at the spine and hip in Caucasian men;¹ and a 2.1 percent lower BMD at the hip in elderly Asian men.⁷ Although variation in outcomes was obtained due to the heterogeneity of the populations, study designs, and sample sizes, clinicians were able to establish a clear association between depression and lowered BMD.

Bone Physiology—A Delicate Balance

In vertebrates, bone is continuously remodeled in a coordinated process of bone resorption performed by specialized cells known as osteoclasts, and bone formation accomplished by other cells known as osteoblasts. Healthy bone tissue reflects a balance between bone building and resorption. An imbalance in the bone remodeling system favoring increased resorption (osteoclast activation) results in lowered BMD,^3,10 leading to osteoporosis.

Proposed Mechanisms for Depression-Induced Bone Loss

Several biological pathways involving alterations to the immune and endocrine systems have been identified to explain the negative impact of depression on bone metabolism.

Sympathetic Nervous System as a Mediator of Bone Loss—the Hebrew University Study

In a fascinating study, researchers at Hebrew University in Jerusalem established that stress-induced depression results in bone loss through activation of the sympathetic nervous system (SNS). Mice subjected to chronic mild stress (CMS) such as noise, overnight illumination, and water deprivation developed not only typical depressive behaviors, such as reduced response to rewards and limited socialization, but also a decrease in bone mass and bone formation caused by a reduction in osteoblast number. When treated with the tricyclic antidepressant imipramine, about half of the mice exhibited a reversal of both depressive behaviors and bone loss.

Even more revealing was the discovery that levels of norepinephrine, a major SNS neurotransmitter, were substantially elevated in the bones of depressed mice. The SNS is involved in the regulation of bone formation and bone mass through b2-adrenergic receptors expressed in osteoblasts. The researchers concluded that the “SNS is the main link transmitting depressive signals from the central nervous system to bone.” In fact, the authors coined the term “neuro-psycho-osteology,” a discipline focused on examining the interactions between the brain, behavior, and the skeleton.¹⁴

Other Neuroendocrine Alterations

In addition to activation of the SNS, other neuroendocrine abnormalities associated with depression include dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and suppression of the somatotrophic (growth hormone) and gonadal axes.

Dysfunction of the HPA axis is common in depressed patients and leads to increased secretion of adrenocorticotrophic hormone (ACTH) and cortisol.^1,8-9 Hypercortisolism results in reduced BMD,^1,3,9 increased osteoclast activity, and a higher rate of bone turnover.^1,10

Reduced levels of the gonadal steroid testosterone are frequently exhibited in depressed patients^3,8,9 in proportion to the severity of the depression.⁹ Altered growth hormone (GH) secretion is also common.^8-9 Both testosterone and GH deficiencies are associated with reduced BMD.^3,8,9

Low Leptin and High Interleukin-6 Levels

Leptin, a hormone secreted by adipose tissue, is involved in regulatory functions related to metabolism and reproduction, and may also play a role in increasing bone formation through osteoblast differentiation.¹ Research points to a relationship between depression, decreased leptin levels and lowered BMD.^1,8-9

Depressive disorders enhance the production of inflammatory cytokines such as Interleukin-6 (IL-6).^1,9 Elevated plasma levels of IL-6 stimulate osteoclastic bone loss and bone resorption.^1,3,9-10

Behavioral Factors

Many depressive behaviors are risk factors for bone loss, including increased smoking and alcohol consumption, reduced physical activity, increased time spent indoors with limited exposure to sunlight (leading to vitamin D deficiency), poor nutrition and inadequate vitamin and mineral intake.^1,9 All of these factors negatively impact bone metabolism.

Comprehensive Natural Approach

A synergistic natural regimen to support bone health secondary to depression involves targeting both conditions simultaneously, using the supplements below, while ensuring a healthy lifestyle, adequate exercise, and good nutrition.

Adequate intake of calcium and vitamin D3 is the foundation for optimal bone health. Calcium is a major component of bone in the form of calcium phosphate crystals known as hydroxyapatite. Vitamin D3 is required to maximize calcium absorption. (Interestingly, low levels of vitamin D3 are associated with depression,¹¹ further establishing the link between mood and bone health.)

Isoflavones are a class of phytoestrogens, plant-derived compounds that mimic the biological effect of estrogen. Ipriflavone is a synthetic soy isoflavone used as a drug in Europe to treat osteoporosis.¹² Studies show that it inhibits bone resorption and enhances bone formation, resulting in an increase in BMD and a decrease in fracture rates.^13-14 In post-menopausal women who typically undergo rapid bone loss, it was demonstrated to maintain bone mass and decrease bone turnover.^15-16

Vitamin K, found together with Ipriflavone, vitamin D3, and calcium hydroxyapatite in Osteoflavone Complex, is essential to the blood-clotting system. It is also important to healthy bone metabolism. In early postmenopausal women, vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption.¹⁷ Daily supplementation with 5 mg of vitamin K1 for 2 to 4 years also protected against fractures in postmenopausal women with osteopenia.¹⁸

DHEA, the most plentiful circulating steroid hormone in the human body,¹⁹ is an ideal natural option for low mood and bone health since it exhibits both anti-depressive and bone-building properties. DHEA enhances BMD by suppression of bone resorption and stimulation of bone formation,²⁰ which may be accomplished by its conversion to estrogen in the osteoblasts of bone tissue.²¹ In clinical studies, DHEA has been shown to increase BMD in patients with osteoporosis.²²

Besides its role in maintaining healthy bones, epidemiological data support a direct relationship between DHEA levels and positive mood.^23-24 In placebo-controlled trials, DHEA proved to be an effective individual or adjunct option in major depression²³ and a useful stand-alone choice in mid-life onset depression.²⁵ It metabolizes to testosterone and estrogen, both of which have mood-enhancing effects of their own.^23,26 Furthermore, DHEA supplementation can help normalize elevated cortisol: DHEA ratios which are implicated in psychiatric diseases.^26-27 Prior to supplementing with DHEA, it’s always a good idea to measure DHEA and cortisol levels by taking a salivary hormone test so that healthy DHEA levels are achieved without increasing levels beyond the normal healthy range. Salivary hormone tests kits are available here.

The natural antidepressant, S-Adeno­sylmethionine (SAMe), is a cellular metabolite formed from the amino acid methionine and adenosine triphosphate, the major cellular energy source. SAMe plays an integral role as a methyl donor in a broad array of cellular reactions involving proteins, phospholipids, DNA and neurotransmitter synthesis.^28-29 Dozens of clinical studies performed since the 1970s have demonstrated SAMe’s mood-lifting properties. SAMe has been shown to be as effective as tricyclic antidepressants, with fewer side effects and faster onset of action.^29-31 And, when taken in combination with tricyclics, SAMe was shown to potentiate and hasten their effect.^31-32

SAMe is essential for the rebuilding of connective tissue and manufacture of cartilage components. Deficient levels of SAMe in joint tissues may be linked to a loss of the gel-like nature and shock absorbing qualities of connective tissues. Studies with SAMe have shown that individuals with osteoarthritis given 1,200 mg per day demonstrated increased cartilage formation over time as demonstrated by Magnetic Resonance Imaging (MRI). In fact, lower doses can be equally effective in treating arthritis, with an average of 400 mg.

Numerous clinical studies indicated that SAMe can reduce pain, stiffness and inflammation associated with degenerative joint problems, as well as enhance the range of motion of specific joints. When compared to nonsteroidal anti-inflammatory drugs (NSAIDs), such as Naproxen or Ibuprofen, SAMe was equally effective in reducing pain and inflammation over a three-month period, and without the gastrointestinal damage caused by these types of drugs.^33-37

Some researchers believe that SAMe also may support healthy homocysteine levels.³⁸ High levels of the amino acid homocysteine, which has been associated with heart disease, also has been linked to osteoporosis. Some research suggests that adequate intracellular SAMe promotes remethylation and transsulfuration of homocysteine.³⁹

Conclusion

Depression sets the stage for a physiological cascade of endocrine and immune alterations that negatively impact bone metabolism. Therefore, anyone suffering from depression should consider a complementary approach to increase mental well-being and support bone health. This complementary approach can incorporate lifestyle changes along with bone-building nutrients such as ipriflavone, vitamin D3, vitamin K, and calcium hydroxyapatite (found in Osteoflavone Complex), supplements clinically demonstrated to build bone and lift mood such as DHEA, and SAMe, which can enhance mental outlook while playing a role in bone and joint health.

References

1. Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Berk M. Depression and bone metabolism. A review. Psychother Psychosom. 2009;78(1):16-25.

2. Mezuk B, Eaton WW, Golden SH. Depression and osteoporosis: epidemiology and potential mediating pathways. Osteoporos Int. 2008 Jan;19(1):1-12.

3. Yirmiya R, Goshen I, Bajayo A, et al. Depression induces bone loss through stimulation of the sympathetic nervous system. Proc Natl Acad Sci USA. 2006 Nov 7;103(45):16876-81.

4. Schweiger U, Deuschle M, Körner A, et al. Low lumbar bone mineral density in patients with major depression.Am J Psychiatry. 1994 Nov;151(11):1691-3.

5. Michelson D, Stratakis C, Hill L, et al. Bone mineral density in women with depression. N Engl J Med. 1996 Oct 17;335(16):1176-81.

6. Jacka FN, Pasco JA, Henry MJ, et al. Depression and bone mineral density in a community sample of perimenopausal women: Geelong Osteoporosis Study. Menopause. 2005 Jan-Feb;12(1):88-91.

7. Wong SY, Lau EM, Lynn H, et al. Depression and bone mineral density: is there a relationship in elderly Asian men? Results from Mr. Os (Hong Kong). Osteoporos Int. 2005 Jun;16(6):610-5.

8. Gold DT, Solimeo S. Osteoporosis and depression: a historical perspective. Curr Osteoporos Rep. 2006 Dec;4(4):134-9.

9. Ilias I, Alesci S, Gold PW, Chrousos GP. Depression and osteoporosis in men: association or casual link? Hormones (Athens). 2006 Jan-Mar;5(1):9-16.

10. Kahl KG, Greggersen W, Rudolf S, et al.Bone mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder. Psychosom Med. 2006 Sep-Oct;68(5):669-74.

11. Berk M, Sanders KM, Pasco JA, et al. Vitamin D deficiency may play a role in depression. Med Hypotheses. 2007;69(6):1316-9.

12. Messina M, Messina V. Soyfoods, soybean isoflavones, and bone health: a brief overview. J Ren Nutr. 2000 Apr;10(2):63-8.

13. Scheiber MD, Rebar RW. Isoflavones and postmenopausal bone health: a viable alternative to estrogen therapy? Menopause. 1999 Fall;6(3):233-41.

14. Head KA. Ipriflavone: an important bone-building isoflavone. Altern Med Rev. 1999 Feb;4(1):10-22.

15. Gennari C, Agnusdei D, Crepaldi G, et al. Effect of ipriflavone--a synthetic derivative of natural isoflavones--on bone mass loss in the early years after menopause. Menopause. 1998 Spring;5(1):9-15.

16. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int. 1997;61 Suppl 1:S19-22.

17. Macdonald HM, McGuigan FE, Lanham-New SA, Fraser WD, Ralston SH, Reid DM. Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women: no evidence of gene-nutrient interaction with apolipoprotein E polymorphisms. Am J Clin Nutr. 2008 May;87(5):1513-20.

18. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008 Oct 14;5(10):e196.

19. Leowattana W. DHEAS as a new diagnostic tool. Clin Chim Acta. 2004 Mar;341(1-2):1-15.

20. Villareal DT.Effects of dehydroepiandrosterone on bone mineral density: what implications for therapy? Treat Endocrinol. 2002;1(6):349-57.

21. Yanase T, Suzuki S, Goto K, Nawata H, Takayanagi. DHEA and bone metabolism. Clin Calcium. 2003 Nov;13(11):1419-24.

22. Sun Y, Mao M, Sun L, Feng Y, Yang J, Shen P. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J. 2002 Mar;115(3):402-4.

23. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone.  Am J Psychiatry. 1999 Apr;156(4):646-9.

24. Barrett-Connor E, von Muhlen D, Laughlin GA, Kripke A. Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: the Rancho Bernardo Study. J Am Geriatr Soc. 1999 Jun;47(6):685-91.

25. Schmidt PJ, Daly RC, Bloch M, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005 Feb;62(2):154-62.

26. Bovenberg SA, van Uum SH, Hermus AR. Dehydroepiandrosterone administration in humans: evidence based? Neth J Med. 2005 Sep;63(8):300-4.

27. Wolkowitz OM, Epel ES, Reus VI. Stress hormone-related psychopathology: pathophysiological and treatment implications. World J Biol Psychiatry. 2001 Jul;2(3):115-43.

28. Lee ES, Charlton CG. 1-Methyl-4-phenyl-pyridinium increases S-adenosyl-L-methionine dependent phospholipid methylation. Pharmacol Biochem Behav. 2001 Sep;70(1):105-14.

29. Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside —molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002 Nov;76(5):1151S-7S.

30. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.

31. Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002 Nov;76(5):1158S-61S.

32. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res. 1992 Dec;44(3):257-62.

33. Hosea Blewett HJ. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis. Crit Rev Food Sci Nutr. 2008 May;48(5):458-63.

34. Glorioso S, et al. Double-blind multicenter study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res. 1985;5:39-49.

35. Marcolongo R, et al. Double-blind multicentre study of the activity of S-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res. 1985; 37:82-94.

36. Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. BMC Musculoskelet Disord. 2004 Feb 26;5:6.

37. Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med. 1987;83 (Suppl. 5A): 81-83.

38. Loehrer FM, Schwab R, Angst CP, et al. Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. J Pharmacol Exp Ther 1997;22:845-50.

39. Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction. Am J Clin Nutr 2002;76:1148S-50S.

Osteoarthritis (OA) is a problem that plagues man and beast. Here, I’m a bit more interested in the beast side—specifically, those wonderful beasts we know as our pets and friends.

OA is an inflammatory response to some stimulus that has occurred in our pet’s body. The most common primary stimulus is either trauma or instability at a joint. It is not uncommon to see arthritis in the form of spondylosis along the spine a few years after a dog has been hit by a vehicle. If a joint is damaged and becomes less stable than normal, a pet’s body responds to stabilize the joint. Inflammation occurs in all the tissue around the joint that is affected by the instability. Hips may have a genetic component that causes the hip to be lax from birth or unstable as the dog grows. That instability will cause tissue reaction as “Mother Nature” works to stabilize the joint. It should be noted that dogs respond with much more reactive tissue than does the human patient.

Secondary to the instability, bone deposition takes place in the soft tissues that surround the joint in an attempt to stabilize the joint. Sadly, all of that reaction will cause long-term joint pain as well.

Conservative care to try to control the pain includes weight management, exercise such as swimming and walking, appropriate rest, nutritional supplements, acupuncture, Chinese or Ayurvedic herbs and non-steroidal anti-inflammatory products such as Rimadyl®, Deramaxx®, Previcox® or Metacam®. Switching from one NSAID to another without a few days of rest to allow the body to clean the first product from the body will increase the risk of stomach problems. Blood panels should be run yearly to evaluate liver and kidney values when your pet is on long-term NSAID therapy.

Interventional care will have us doing hip, stifle (knee) or elbow replacement surgery to relieve the pain. While these surgeries have progressed from the first versions, they are more commonly used as a last resort. However, some young dogs with severe hip laxity may benefit from having a hip replacement after 10 months of age so they don’t have to go through a life of pain.

Most folks who have been reading about what can help our pets live more comfortably have heard of glucosamine, chondroitin and MSM. In conjunction with these, there are other natural substances that may help such as omega-3-fatty acids (EPA and DHA), which decrease inflammation, Boswellia (Frankincense), which has been used for arthritis since the time of Christ, and bromelain, which is a protease enzyme that blocks some proinflammatory metabolites. Other useful items include antioxidants such as vitamins C and E; hydrolyzed collagen, a gelatin product that was found to be helpful in a German study; Ginger extract, shown to have moderate effect in the human model on knee pain; and hyaluronic acid, which has been used for years in arthritic horses.

Nutri-Joint for Pets supplies many of the noted materials and is very helpful. I prefer to have my patients on these types of products before I start them on NSAIDS. It may take less of the NSAID to relieve the pain when these products are used in conjunction.

CDP Choline (cytidine-5’-diphosphocholine, or citicoline) is a unique form of the essential nutrient choline that helps regulate bioelectrical activities in the brain. Over the last thirty years, CDP Choline has been studied in numerous animal and human clinical trials for its potential to enhance brain and cognitive function in a variety of clinical situations including memory loss, dementia, stroke, and head trauma. CDP Choline has achieved promising results in older individuals with inefficient memory, cognitive deficits, and early-stage Alzheimer’s. Therefore, it is worthwhile to discuss the many facets of CDP Choline’s role in cognition.

Aging and Memory

Difficulties with attention, learning, and recall are considered typical for most people in middle age and older. Starting around age fifty, we tend to experience brain changes that directly affect memory and cognitive function. It is now known that as we age there are decreases in the number of synapses between neurons and in the number and functionality of receptors (where chemical messengers are received on neurons). It is also known that, with aging, the availability of certain brain neurotransmitters is diminished, and that proper functioning of the bundles of neuronal fibers that transmit messages (white matter pathways) is impaired. All of these age-associated brain changes hinder communication between neurons and ultimately decrease our ability to pay attention, learn, and remember.

However, even in the face of these brain changes, successful aging without disruptive cognitive decline is definitely possible. Even centenarians may not exhibit memory problems despite the fact that their brains might show the hallmark features of degenerative brain disease, or Alzheimer’s, on autopsy. Genetics, environment, and lifestyle all play roles in determining why some people in their nineties are nearly as sharp as they have always been while others begin to deteriorate in their fifties.

The Role of CDP Choline

Studies have shown that supplementation with CDP Choline may be one way to modify this disruptive process of age-related cognitive decline. Produced naturally inside the body, CDP Choline is a compound used to synthesize phospholipids, the essential building blocks of all biological membrane systems. Phosphatidylcholine, one of the primary phospholipids synthesized by CDP Choline, is an integral component of cellular membranes that adds strength and fluidity to cells. Phosphatidylcholine in brain cell membranes decreases with age. Studies indicate that CDP Choline supplementation may increase phosphatidylcholine synthesis and might reverse this age-related loss.1

CDP Choline (citicoline) is synthesized and marketed in the US as a dietary supplement, and as a drug in Japan. In Europe, citicoline is approved and sold as a drug. It is frequently prescribed for cognitive impairment in several European countries, as well as for stroke and head trauma recovery, and other neurological disorders.

In addition to its role in producing phosphatidylcholine, citicoline may also serve as a choline donor for the synthesis of acetylcholine, a neurotransmitter that plays an important role in both learning and memory. Animal studies have indicated that it may increase dopamine and enhance the amount of bioactive reduced glutathione levels as well. Glutathione is a potent antioxidant, especially in the brain, while dopamine, a neurotransmitter, is essential for the healthy functioning of the central nervous system; it has effects on emotion, perception and movement. When taken as a supplement (or drug), citicoline appears to help preserve the structure and function of neuron membranes and possibly decrease the progression of neuron cell damage that occurs, for example, after a stroke.

Several clinical studies demonstrate that citicoline can be used successfully in some patients with stroke, brain trauma, chronic cerebrovascular disorders, and vascular dementia, as well as for some elderly non-demented individuals with memory deficits.

CDP Choline and Cognition

Among the aging baby boom population, memory problems are some of the most feared age-related health issues. Experts continue to disagree on what, if any, relationship exists between age-related memory loss (which is not considered a disorder), and the two memory disorders, mild cognitive impairment and dementia. As it now stands, the official term for the normal memory problems associated with aging is “age-associated memory impairment.”

Further studies looking at the full benefits and efficacy of CDP Choline in improving memory loss in “healthy” older adults are still needed. The few studies that have looked specifically at this subset, however, have demonstrated improved memory performance among elderly adults taking CDP Choline.

Prevention of memory loss has become a growing area of research. Because of CDP Choline’s intermediary role in phosphatidylcholine synthesis, early researchers theorized that it could restore memory function by repairing age-related changes within the brain neuronal membrane. One of the earliest studies evaluating CDP Choline’s potential as a treatment for age-related memory loss was a double-blind, placebo-controlled, randomized trial involving 84 patients, mean age 72, with mild to moderate memory deficits but no other cognitive dysfunctions. Memory loss was assessed using the Mini Mental State Examination (MMSE). After being administered 1,000 mg CDP Choline daily for six weeks, subjects were assessed with the Randt Memory Test for changes in immediate recall, delayed recall, and global memory efficiency. Global memory efficiency improved, primarily due to the subjects’ significantly improved ability to learn new information.2

A randomized, placebo-controlled, double-blind trial using 95 healthy volunteers, ages 50-85, tested CDP Choline’s effect on memory.3 Subjects were recruited from the clinical research center at MIT and were screened to have no dementia. The researchers noted that a few of the patients might have met the criteria for age-associated memory impairment (a decline in memory, especially in verbal memory, can be observed in normal elderly people as well as in elderly with mild cognitive impairments).

The study had two phases. In the first phase, all subjects took 1,000 mg citicoline or placebo per day for three months. A portion of the group with relatively poor memories was recruited for the second phase and given either a placebo or 2,000 mg citicoline per day for three months. After the first phase, improvement with citicoline occurred only in the people with poor memories, who showed gains in delayed recall and logical memory. At the end of the second phase, verbal memory clearly improved in the 2,000 mg group, suggesting that 2,000 mg daily may be a more effective dose for people with age-associated memory impairment. The researchers concluded that in subjects with relatively inefficient memory, citicoline facilitated memory acquisition and retention.

A third placebo-controlled clinical trial demonstrated that citicoline possesses memory-enhancing activity in free recall tests (but not in recognition tests) at doses ranging from 300-1,000 mg per day. Four weeks of citicoline supplementation significantly improved the ability of 24 elderly subjects with memory deficits to recall words and objects after viewing them for two seconds each. No significant improvement was observed, however, for recognition tasks in which patients had to recall previously viewed words and objects randomly mixed with non-viewed items.4

CDP Choline has gone through a number of clinical trials to assess its effectiveness in cognitive enhancement in subjects with dementia, including dementia of the Alzheimer’s type as well as vascular, or multi-infarct, dementia. For instance, a double-blind, placebo-controlled trial tested the efficacy of CDP Choline in improving symptoms in patients with mild to moderate Alzheimer’s-type dementia. Thirty patients were administered 1,000 mg CDP Choline daily for twelve weeks. Using four different scales, researchers determined there were changes between the CDP Choline and placebo groups, but the changes were not statistically significant. Results were better in patients with more mild mental deterioration.5 In 20 patients with Alzheimer’s, a double-blind study found that spatial-temporal orientation also significantly improved, while Mini Mental State Examination scores showed statistically significant increases only in a patient subgroup with early-onset Alzheimer’s.6

To determine the overall clinical efficacy of CDP Choline for the symptoms of cognitive, emotional, and behavioral impairment in older patients with dementia or mild cognitive impairment, a large meta-analysis in 2005 examined the data from 14 double-blind, placebo-controlled clinical studies. The results indicated a positive and consistent effect of CDP Choline on memory and behavior, at least in the short to medium turn, since none of the studies available were assessing long-term efficacy. The authors found the evidence to be especially strong for the efficacy of CDP Choline in patients with cognitive impairments related to cerebral vascular disorders, such as the complications of stroke.7

Strokes

Reduced blood flow to the brain, as occurs during a stroke, causes the degradation of phosphatidylcholine to free fatty acids (particularly the inflammation-inducing arachadonic acid) and free radicals. CDP Choline enhances the re-synthesis of phospholipids, primarily phosphatidylcholine, of cell membranes. It has shown promise for reducing stroke-related injury by stabilizing cell membranes long enough to prevent large-scale brain cell damage after stroke. A review published in 2005 identified thirteen stroke clinical trials of CDP Choline since 1980 in Europe, Japan, and the US.8 Both European and Japanese trials found that CDP Choline significantly improved neurological function and helped speed motor and cognitive recovery. A multicenter double-blind, placebo-controlled study was conducted to evaluate possible clinical benefits of CDP Choline in patients with acute cerebral infarction and disturbances of consciousness. Patients were allocated randomly to either CDP Choline (1,000 mg per day i.v. once daily for 14 days) or with placebo (physiological saline). One hundred thirty-three patients received CDP Choline treatment, and 139 received placebo. The group given CDP Choline showed significant improvements in level of consciousness compared with the placebo-treated group. CDP Choline was found to be entirely safe.9

Other studies evaluating the effects of CDP Choline after strokes have resulted in different outcomes. In a recent U.S. clinical trial involving nearly 400 patients in 33 centers nationwide, patients were first given citicoline or a placebo within a few hours of their stroke, then for six weeks afterward, with a six-week, post-treatment follow-up period.10 Results for the entire group as a whole showed no statistically significant difference in five areas—including full recovery and mortality rates, neurological and cognitive function—between patients with stroke who were given citicoline, and those who were given a placebo. However, it was found effective in the subgroup of the subjects with moderate to severe strokes. The same group of researchers then conducted an even larger trial using 2,000 mg citicoline for six weeks following a stroke. Again, they found that citicoline was ineffective in improving the outcome of acute stroke patients.11 The review authors concluded that further studies are essential before making any conclusions on using CDP Choline after strokes.

Conclusion

CDP Choline is a form of the essential nutrient choline and a precursor of phosphatidylcholine and acetylcholine. Oral CDP Choline supplementation has been found to promote phospholipid biosynthesis, increase cerebral blood flow, inhibit cytotoxic (cell-destroying) free fatty acids and formation of diacylglycerol (a precursor to triglyceride formation), and promote healthy brain bioelectrical activity. In clinical studies, it has improved verbal memory functioning in older individuals with relatively inefficient memories and has been very well tolerated. The latest meta-analysis found no noticeable side effects evidenced in the fourteen various studies evaluated.7

Alexander G. Schauss, PhD, FACN,

Dr. Schauss is the Director of Natural and Medicinal Products Research, in Puyallup, Washington. He has previously held the rank of an Adjunct Research Professor of Botanical Medicine and Clinical Professor of Natural Products Research at the National College of Naturopathic Medicine in Portland, Oregon, as well as Associate Professor of Research at the Southwest College of Naturopathic Medicine and Health Sciences in Tempe, Arizona. Dr. Schauss has been a member of the National Institutes of Health (NIH) Office of Alternative Medicine (OAM) Advisory Council (AMPAC); and a reviewer of botanical standards and information monographs for the U.S. Pharmacopoeia Convention (USP). In 1985, Dr. Schauss was appointed by the US government to represent the United States as a voting member to the World Health Organization (WHO) Study Group on Health Promotion. He is the author or a co-author of more than 140 papers or works that have appeared in various scientific journals as well as books covering such topics as his discovery that Acai (Euterpe oleracea) contains the richest amount of antioxidants found in any food, and the problem of intra-abdominal obesity (the potbelly) in men. Dr. Schauss’ many accomplishments over a span of three decades were formally recognized when he received the Linus Pauling Lecture Award for contributions in the medical sciences in 2005 from the American College for the Advancement of Medicine.

References

1. Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002;161: 248-54.

2. Agnoli A, Bruno G, Fioravanti M, et al. Therapeutic approach to senile memory impairment: a double-blind clinical trial with CDP choline. In: Wurtman RJ, Corkin S, Growden JH, eds. Alzheimer’s Disease: Proceedings of the Fifth Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging. Boston: Birkhauser. 1989: 649-654.

3. Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Arch Neurol. 1996; 53: 441-8.

4. Alvarez XA, Laredo M, Corzo D, Fernandez-Novoa L, Mouzo R, Perea JE, Daniele D, Cacabelos R. Citicoline improves memory performance in elderly subjects. Meth Find Exp clin Pharmacol. 1997;19: 201-210.

5. Alvarez XA, Mouzo R, Pichel V, Perez P, Laredo M, Fernandez-Novoa L, Corzo L, Zas R, Alcaraz M, Secades J J, Lozano R, Cacabelos R. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer’s disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999;21: 633-44.

6. Caamano J, Gomez MJ, Franco A, Cacabelos R. Effects of CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimer’s disease. Methods Find Exp Clin Pharmacol. 1994;16: 211-8.

7. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. 2005. Cochrane Database Syst Rev. CD000269.

8. Adibhatla RM, Hatcher JF. Cytidine 5’-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res. 2005 Jan;30(1):15-23.

9. Tazaki Y, Sakai F, Otomo E, Kutsuzawa T, Kameyama M, Omae T, Fujishima M, Sakuma A. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke. 1988. 19: 211-6.

10. Clark WM, Williams BJ, Selzer KA, Zweifler RM, Sabounjian LA, Gammans RE. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke. 1999;30: 2592-7.

11. Clark WM, Wechsler LR, Sabounjian LA, Schwiderski UE. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology. 2001;57: 1595-1602.

Benfotiamine May Improve Eye Health

The condition known as uvetis, inflammation of the interior layer of the eye, is estimated to be responsible for approximately 10 percent of the blindness in the United States. Although in many cases the cause of uvetis is unknown, numerous conditions are linked to this inflammation in the eye, including ankylosing spondylitis, Behçet’s disease, herpes simplex and herpes zoster, inflammatory bowel disease, juvenile rheumatoid arthritis, Kawasaki’s disease, Lyme disease, multiple sclerosis, sarcoidosis and systemic lupus erythematosus.

Now, a new study has shown that the lipid soluble form of thiamine known as benfotiamine may suppress the inflammation thought to lead up to uvetis.

Researchers induced uvetis in the eyes of one group of rats. In another group, they again induced the inflammatory condition in the eyes of the animals, but in this group they also gave the animals benfotiamine. The scientists left another group as untreated controls. Twenty-four hours after the researchers induced uvetis in the animals, the changes in their eyes were examined.

In the uvetis group not given benfotiamine, inflammatory cytokines and chemokines were significantly elevated compared to controls. Benfotiamine treatment suppressed these increases. Similarly, benfotiamine significantly inhibited the uvetis-caused increased expression of other inflammatory markers such as COX-2 in the ciliary body and retinal wall of the eyes and suppressed NF-KappaB, a protein complex involved in inflammation.

The researchers concluded, “These results suggest that benfotiamine suppresses oxidative stress-induced NF-kappaB dependent inflammatory signaling leading to uveitis and therefore it could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.”

Reference:
Yadav UC, Subramanyam S, Ramana KV. Lipophilic Vitamin-B1 Analogue Benfotiamine Prevents Endotoxin-Induced Uveitis in Rats. Invest Ophthalmol Vis Sci. 2009 Jan 10. Published online ahead of print.

Carotenoid Intake Linked to Strong Bones

An increased intake of the plant compounds known as carotenoids can inhibit bone loss in men and women, researchers report in a new study.

In vitro and in vivo studies suggest that carotenoids may inhibit bone resorption and stimulate proliferation and differentiation of the bone-building cells known as osteoblasts. Until now, few studies have examined the association between carotenoid intake (other than beta-carotene) and bone mineral density (BMD).

In the current study, which included data from 334 men and 540 women with an average age of 75, researchers measured the subjects’ intake of total and individual carotenoids, including alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein plus zeaxanthin by using a 126-item food frequency questionnaire. They then compared the carotenoid intakes with the subjects’ bone mineral density at the hip, spine, and radial shaft.

The results indicated female subjects who consumed the most of the carotenoid lycopene experienced the least bone loss in the lumbar spine compared to those who consumed lower amounts of lycopene. In men, lycopene intake also was associated with greater bone mineral density in the hips. Bone mineral density in the hips of men was also linked to intakes of total carotenoids, beta-carotene, and lutein plus zeaxanthin.

Previous reports have suggested that oxidative stress may increase bone resorption, the process by which bone is broken down. Consequently, the study authors believe carotenoid’s bone-protective effects may be due in part to the plant compounds’ antioxidant abilities.

Reference:
Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Inverse association of carotenoid intakes with 4-y change in bone mineral density in elderly men and women: the Framingham Osteoporosis Study. Am J Clin Nutr. 2009 Jan;89(1):416-24.

The formula CAROTeam^™ delivers a potent supply of naturally occurring carotenoids, including lycopene, beta carotene and lutein.

Astragalus May Act as a Fatigue-Fighting Nutrient

The botanical astragalus may improve immunity and enhance energy levels in chronic fatigue syndrome, a new study suggests.

Because alteration of immune function may be associated with chronic fatigue syndrome (CFS), researchers set out to determine the effects of astragalus membranaceus on energy levels and immune function in an animal model of this condition. Chronic fatigue was induced in rats by restricting the animals’ food intake and having the rodents participate in forced swimming for six weeks. This caused the animals to have an atrophied spleen associated with a significantly decreased spleen/body weight ratio and reduced spleen cells proliferation compared to controls. The spleen is an organ critical in the immune process, and low activity in the spleen is associated with increased infections. The rats with chronic fatigue also produced an abnormal number of cytokines, important immune system proteins and signaling molecules.

Astragalus given orally at 20, 50 and 100 mg/kg body weight once per day for 6 weeks increased the reduced spleen cell proliferation that occurred in the animals with chronic fatigue. Supplementation with astragalus also significantly counteracted the abnormal cytokine production and helped to normalize immune response. Furthermore, rats receiving astragalus exhibited higher endurance capacity to swim when compared with those not given the botanical extract.

The researchers concluded “Alterations of immune function may be associated with chronic fatigue syndrome” and that the effects of astragalus against chronic fatigue may be attributable to its ability to balance the abnormal cytokine levels.

Reference:
Kuo YH, Tsai WJ, Loke SH, Wu TS, Chiou WF. Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming. J Ethnopharmacol. 2008 Dec 6. Published online ahead of print.

Omega-3s Linked to Health of Menopausal Women

Two new studies reveal that ethyl eicosapentaenoic acid (EPA), the omega-3 fatty acid derived from fish oil, may improve mood and ease hot flashes in menopausal women.

Psychological distress and depressive symptoms often occur during menopause and an emerging body of evidence indicates that omega-3 fatty acids may help alleviate depression. Consequently, researchers conducted two studies, the first to determine if ethyl EPA could improve depressive symptoms in menopausal women and the second to investigate the omega-3 fatty acid’s effect on hot flashes.

In the first study, researchers compared the effect of ethyl EPA supplementation or a placebo on psychological distress and depressive symptoms in middle-aged women. The researchers randomly divided women with moderate-to-severe psychological distress into two groups. One group of 59 women received 1.05 grams of ethyl EPA per day plus 0.15 grams of ethyl-docosahexaenoic acid (ethyl DHA), while 61 women received a placebo for 8 weeks.

The researchers found that menopausal women who suffered from psychological distress experienced a significant improvement in both their psychological distress scores and their depressive symptoms after taking the ethyl EPA compared to the women taking the placebo.

“To our knowledge,” the researchers wrote, “this is the first trial of n-3 supplementation in the treatment of PD [psychological distress] and depressive symptoms in middle-aged women.”

The researchers conducted a second study using the subjects from the first study to determine whether ethyl EPA had an effect on hot flashes and quality of life among middle-aged menopausal women between the ages of 40 and 55. Only women who were experiencing hot flashes were included in this study.

The scientists gave 45 women ethyl EPA and 46 women a placebo for eight weeks. At baseline, the average number of hot flashes was 2.8 per day. After 8 weeks, hot flash frequency and severity score decreased significantly in the ethyl EPA group compared with the placebo group. Frequency of hot flashes declined by a mean of 1.58 per day in the ethyl EPA group while in the placebo group there was a decline of only 0.50 per day. The odds of having the hot flashes were reduced by about three times among those taking ethyl EPA compared to those taking the placebo.

According to the study authors, “Supplementation with Ethyl-EPA omega-3 fatty acid reduced hot flash frequency and improved the hot flash score relative to placebo.”

The researchers called for additional clinical trials specifically designed to evaluate the effects of omega-3 fatty acids in women who are even more symptomatic than those who took part in this trial.

References:

Lucas M, Asselin G, Mérette C, Poulin MJ, Dodin S. Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr. 2009 Feb;89(2):641-51.

Lucas M, Asselin G, Mérette C, Poulin MJ, Dodin S. Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause. To be published in print March 2009;16(2). Published Online ahead of print 2008 Nov 20.

Review Examines Glucosamine and Chondroitin’s Role in Joint Health

Researchers from the Department of Orthopedic Surgery at the University of Southern California, Los Angeles, have conducted a review of the scientific literature to determine the effectiveness of glucosamine and chondroitin sulfate in knee osteoarthritis (OA).

The reviewers critically evaluated the published clinical studies on glucosamine and chondroitin sulfate’s use in osteoarthritis. After examining the literature, they found that almost every included trial confirmed that the safety of these compounds was equal to the placebo. In the studies satisfying the scientists’ inclusion criteria, glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing osteoarthritis pain and improving joint function. However, when the substances were given together, many studies confirmed osteoarthritis pain relief with glucosamine and chondroitin sulfate use.

These findings led the reviewers to conclude, “The excellent safety profile of glucosamine and chondroitin sulfate therapy should be discussed with patients, and these supplements may serve a role as an initial treatment modality for many OA patients.”

Reference:
Vangsness CT Jr, Spiker W, Erickson J. A review of evidence-based medicine for glucosamine and chondroitin sulfate use in knee osteoarthritis. Arthroscopy. 2009 Jan;25(1):86-94.

Quercetin Improves Heart Health

The bioflavonoid quercetin is involved in regulating a gene that protects against LDL cholesterol oxidation, a new study has revealed.

The gene paraoxonase 1 (PON1) protects low-density lipoprotein (LDL) cholesterol from undergoing the oxidation process. PON1 therefore plays a role in heart health because it is the oxidation process that is linked to LDL cholesterol’s heart damaging effects. PON1 also is a major anti-atherosclerotic protein component of the “good” cholesterol, high-density lipoprotein (HDL) cholesterol.

In a new study, researchers explored the role that quercetin plays in regulating PON1 expression in rats. The scientists found that compared to the control group, the rats fed quercetin for four weeks experienced a 35 percent increase in PON1 expression in the liver. Serum PON1 activities also increased by 29 percent. In the quercetin group, the activity of homocysteine thiolactonase (HCTL), an enzyme associated with breaking down homocysteine, an amino acid implicated in heart disease, increased by 23 percent.

Furthermore, quercetin appeared to assist HDL in offsetting the negative effects of LDL in that it took longer for the LDL to oxidize when it was exposed to the plasma HDL from the quercetin-fed group compared to the HDL from the control group.

The study authors concluded, “Our data suggest that quercetin has antiatherogenic effect by up regulating PON1 gene expression and its protective capacity against LDL oxidation.”

Reference:
Gong M, Garige M, Varatharajalu R, Marmillot P, Gottipatti C, Leckey LC, Lakshman RM. Quercetin up-regulates paraoxonase 1 gene expression with concomitant protection against LDL oxidation. Biochem Biophys Res Commun. 2009 Jan 10. Published Online Ahead of Print.

Quercetin is found along with other synergistic ingredients in the formulas QuerCelain^®, Bioflavonoid Complex with Quercetin and Extension Resveratrol.

Vitamin D3 Linked to Cognitive Enhancement

Vitamin D3 deficiency has been linked to a number of conditions, including osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases. There is also some evidence that the vitamin may lower the incidence of type 1 diabetes. Now, researchers have unearthed another possible role for vitamin D3.

Some small clinical studies have indicated that serum 25-hydroxyvitamin D [25(OH)D] concentration, an effective indicator of vitamin D status, may be associated with dementia and cognitive function. However, researchers undertook the current study because evidence from large-scale and well-designed trials was lacking.

In the researchers’ recent large-scale study, they evaluated 1,766 adults aged 65 years and older who were participating in the Health Survey for England 2000. They then assessed cognitive impairment in the subjects using what’s known as the Abbreviated Mental Test Score and measured serum levels of 25-hydroxyvitamin D, a test used to determine vitamin D3 levels in the body.

The scientists found that subjects who had normal cognitive function had higher levels of serum vitamin D3 than those who were cognitively impaired. The researchers also found that compared to those participants who had higher levels of vitamin D3, those with the lowest levels were more than twice as likely to be cognitively impaired.

The large-scale study added to data from previous smaller studies, which support roles for vitamin D3 in brain development and neuroprotection.

Reference:
Llewellyn DJ, Langa K, Lang I. Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment. J Geriatr Psychiatry Neurol. 2008 Dec 10. Published online ahead of print.

Cinnamon May Improve Insulin Response

Blood sugar control may be improved in people who consume cinnamon supplements, according to the results of a new study.

Past studies have shown that cinnamon can improve fasting glucose in humans. However, data on how cinnamon affects insulin sensitivity is limited. Insulin resistance occurs when cells lose their sensitivity to insulin. When this occurs, sugar is unable to enter the cells. The cells are unable to respond to the message that insulin is trying to send, and in an attempt to compensate, the pancreas produces higher and higher amounts of insulin. During insulin resistance, sugar builds up in the blood to elevated levels.

In the current study, researchers sought to determine how cinnamon can affect insulin sensitivity. Eight male volunteers in their 20s underwent two, 14-day interventions involving cinnamon or placebo supplementation. Placebo supplementation was continued for 5 days following this 14-day period. Oral glucose tolerance tests were performed on days 0, 1, 14, 16, 18, and 20.

Cinnamon ingestion reduced the glucose response to the oral glucose tolerance test on day 1 and day 14. Cinnamon ingestion also reduced insulin responses to the oral glucose tolerance test on day 14 as well as improving insulin sensitivity on day 14. The improvements were lost after the subjects stopped taking the cinnamon supplements.

The researchers concluded that cinnamon may improve glycemic control and insulin sensitivity and that the effects are no longer observed after cinnamon is stopped.

Reference:
Solomon TP, Blannin AK. Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans. Eur J Appl Physiol. 2009 Jan 22. Eur J Appl Physiol. 2009 Jan 22. Published Online Ahead of Print.

Green Tea Plays Important Role in Women’s Health

Women who drink green tea may have a reduced risk of developing breast cancer, a new study has noted.

Past epidemiological and animal data suggest that tea and tea polyphenols may be protective against various cancers. Consequently, researchers from the Vanderbilt School of Medicine undertook the current study to further explore the potential link between green tea consumption and breast cancer.

The researchers compared the diets of 3,454 women with breast cancer and 3,474 healthy controls aged between 20 and 74.

Compared with nondrinkers, regular green tea drinkers experienced a modest, 12 percent decreased risk for breast cancer. Among premenopausal women, the reduced risk was associated with the number of years they had been drinking green tea. The study authors also noted a dose-response relationship, with the women who drank the most tea per month experiencing the greatest reduced risk.

Reference:
Shrubsole MJ, Lu W, Chen Z, Shu XO, Zheng Y, Dai Q, Cai Q, Gu K, Ruan ZX, Gao YT, Zheng W. Drinking green tea modestly reduces breast cancer risk. J Nutr. 2009 Feb;139(2):310-6.

Individuals who do not want to consume large amounts of green tea can take green tea extract capsules. Our green tea extract is very low in caffeine and has a high EGCG content.

Stephania Tetrandra May Improve Gastrointestinal Health

Tetrandrine, an important component of the botanical Stephania tetrandra, improved the symptoms of ulcerative colitis in a new study using an animal model of this inflammatory bowel disease.

In past studies, activation of nuclear factor (NF)-kappaB has been shown to play a critical role in the development of ulcerative colitis (UC). Tetrandrine, isolated from the herb Stephania tetrandra, has been demonstrated to be a potent inhibitor of NF-kappaB activation.

In the current study, researchers investigated the effects of tetrandrine in an experimental model of ulcerative colitis in mice. Researchers induced colitis in the animals by administering dextran sulfate sodium (DSS). The study authors then administered tetrandrine and noted how the botanical-derived compound affected the disease activity index (DAI) and histological score, which refers to how disease affects the microscopic anatomy of cells and tissues. NF-kappaB DNA binding activity also was assessed.

A significant improvement was observed in the disease activity index and histological score in mice given tetrandrine. Furthermore, the increase in NF-kappaB DNA binding activity was significantly reduced following administration of tetrandrine. Activity of IL-1beta and TNF-alpha also was significantly reduced following administration of tetrandrine. IL-1beta and TNF-alpha are both cytokines (cellular signaling molecules) involved in the inflammatory response. Overproduction of tumor necrosis factor-alpha (TNF-alpha) has been implicated in a variety of human diseases. IL-beta production in peripheral tissue has been associated with hyperalgesia (increased sensitivity to pain).

According to the researchers, “The administration of tetrandrine leads to an amelioration of DSS-induced colitis, suggesting administration of tetrandrine may provide a therapeutic approach for UC.”

Reference:
Zhang DK, Cheng LN, Huang XL, Shi W, Xiang JY, Gan HT. Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor -kappaB activation. Int J Colorectal Dis. 2009 Jan;24(1):5-12.

Stephania tetrandra is found with other inflammation-modulating botanicals in the Advanced Inflammation Control formula.