Dr. Tori Hudson, N.D.

For most bladder infections, a natural approach is usually very effective and the infection resolves quickly without recurrence or complications. The primary goals of a natural therapeutics approach are to:

• enhance the individual’s internal defenses against the infection by providing immune support
• restore vaginal and bladder microflora, enhancing the flow of urine
• promote a proper pH
• prevent bacteria from adhering to the bladder epithelium

Increasing the urinary flow is easily accomplished by increasing the quantity of liquids. Water and herbal teas related to the treatment goals are the most logical choices. 64 ounces per day is the common recommendation.

No natural approach to cystitis would be complete without mention of cranberry. Women have used cranberry juice as a home remedy for decades. Several studies have shown that cranberries and cranberry juice are effective in women with active urinary tract infections. In one study, 16 ounces of cranberry juice daily was effective in 73% of individuals with an active infection.1 Cranberry has also been shown to reduce the ability of E. coli to adhere to the lining of the bladder and urethra. Many people still think that the action of cranberry juice is due to acidifying the urine. However, recent studies have shown that components in cranberry juice reduce the ability of E. coli to adhere to the lining of the bladder and urethra.

One of the most useful herbs for bladder infection is uva ursi (Arctostaphylos uva ursi), also known as bearberry or upland cranberry. The antiseptic, antibacterial and astringent activity of uva ursi is largely due to its arbutin content. Uva ursi is especially active against E. coli as well as having diuretic properties. Uva ursi has also been used with recurrent bladder infections and was very effective in a double-blind study of 57 women. After one year, five of twenty-seven women had a recurrence in the placebo group while none of thirty women had a recurrence in the uva ursi group. Pipsissewa, a Native remedy of the Pacific Northwest, is a traditional remedy for urinary infections. It’s mildly antimicrobial effects have been attributed to its arbutin content.

Oregon grape root is another useful herb in bladder infections due to its antimicrobial properties. Specifically, it has demonstrated antibacterial activity against E. Coli and Proteus species. Oregon grape root and Goldenseal are rich sources of one of the most significant plant based antibacterial active constituents, berberine. Berberine is effective against many bacteria and is also able to fight infections by inhibiting the bacteria from adhering to the host cell.

Other botanicals have been traditionally used for bladder infections with positive effect. The water-soluble mucilage herbs are known to be soothing to the irritated uroepithelium and reduce inflammation. These include corn silk for its soothing and cooling effect on the urinary tract; marshmallow root due to its content of mucilage, which can form a protective layer on the lining of the bladder; and even plantain leaf with its high percentage of mucilage and allantoin. Additional antimicrobial herbs for the bladder include bucchu, myrrh, propolis and juniper berry. Numerous immune stimulants may be helpful including echinacea, osha and wild indigo root. Bladder tonics stimulate the flow of blood and nutrients to the urinary tract and may be useful adjunct herbs. These include nettles leaves, goldenrod, kava kava and horsetail. Dandelion leaf, bucchu and parsley root have diuretic effects and increase the flow of urine to help flush the bacteria.

Probiotics, or “live micro-organisms that confer a health benefit for the host” for the prevention of urinary tract infections (UTIs) are useful in establishing and maintaining a proper bladder pH and enhancing a normal ecology of the vagina, urethra and bladder. Lactobacilli dominate the urogenital flora of healthy reproductive aged women. Several in vitro and in vivo studies support the therapeutic benefit of several strains of lactobacilli on the restoration of vaginal ecology and flora and the prevention of recurrent bladder infections. Lactobacillus rhamnosus and Lactobacillus fermentum appear to be the most effective.

References

• Prodromos P, Brusch C, Ceresia G. Cranberry Juice in the treatment of urinary tract infections. Southwest Med 1968; 47:17.
• Sternlief P. Cranberry Juice in renal disease. New Engl J Med 1963;268:57
• Moen D. Observations on the effectiveness of cranberry juice in urinary infections. Wisconsin Med J 1962;61:282.
• Ofek I, Goldhar J, et al. Anti-Escherichia coli adhesion activity of cranberry and blueberry juices. NEJM 1991; 324:1599
• Zafiri D, Ofek I, et al. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Chemother 1989;33:92-98.
• Sobota A. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urology 1984; 131:1013-1016.
• Ofek I, et al. Anti-escherichia activity of cranberry and blueberry juices. NEJM 1991; 324:1599.
• Larsson B, Jonasson A, Fianu S. Prophylactic effect of UVA-E in women with recurrent cystitis: A Preliminary Report. Curr Ther Res 1993;53:441-443.
• Amin A, Subbaiah T, Abbasi K. Berberine Sulfate: Antimicrobial activity, bioassay, and mode of action. Can J Microbiol 1969;15:1067-1076.
• Johnson C, Johnson G, Poe C. Toxicity of alkaloids to certain bacteria. Acta Pharmacol Toxicol 1952;8:71-78.
• Hahn F, Ciak J. Berberine. Antibiotics 1976;3:577-588
• Falagas M, Betsi G, Tokas T, Athanasiou S. Probiotics for prevention of recurrent urinary tract infections in women. Drugs 2006;66(9):1253-1261.

Polycystic ovarian syndrome (PCOS), is not really classified as a disease, because it is not a specific and constant set of symptoms and physical characteristics. Rather, it is better described as a syndrome, with a collection of symptoms, physical characteristics and laboratory findings. There are two consistent aspects of PCOS: hyper-androgenism and a lack of or infrequent ovulation. The most common characteristics of PCOS are obesity, hirsutism, and irregular/infrequent/lack of ovulation and thus irregular menses and poor fertility. Over 95% of women who have all three of the classic signs of obesity, hirsutism and/or irregular menses, have PCOS. One of the problems with PCOS, is that many women have this syndrome, but don’t have all three of the classic signs. Not all women with PCOS are obese, in fact not even 50%. Many PCOS women are of normal weight or even underweight, have no excess hair growth on the face of chest or legs, and may even have pretty regular menses.

The current diagnostic criteria from the 2003 Rotterdam PCOS consensus workshop is that at least two of the following three features must exist (and exclusion of other etiologies of their hyperandrogenism and/or amenorrhea/oligomenorrhea):

• Oligo- or anovulation
• Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries (> 12 follicles 2-9 mm or volume > 10 ml)

So many variables exist with this syndrome, that it’s no wonder it can be hard to come up with a definitive diagnosis. There can be other manifestations of hyper-androgenism (hair loss, acne) in And, not all PCOS women are infertile because of random unpredictable ovulation. Yet PCOS is likely the single most common cause of a lack of ovulation, leading to abnormal menstrual cycles and infertility

An important feature of PCOS is that there are some hormonal changes including hyperinsulinism and/or insulin resistance and elevated total testosterone. Total testosterone is not a very accurate laboratory test in women, and the range of normal has not been established, so testing testosterone levels has limited value.

The underlying cause of PCOS is varied and still evolving. What we currently know is the following:

1. elevated secretions of androgens from the ovaries and/or adrenal glands that overwhelm the body’s ability to convert these androgens to estrogen
2. abnormal ratios of the pituitary hormones, leutinizing hormone (LH) to follicle stimulating hormone (FSH)
3. failure of the monthly maturing of a follicle in the ovaries
4. a resistance to insulin
5. likely a genetically driven defect in the action of insulin

Metabolic dysfunctions including abnormalities in lipid levels, insulin and blood sugar levels, and high blood pressure are significant medical problems, that can be related to the underlying syndrome of PCOS.

Besides the potential changes including increased body weight, acne, facial hair, hair thinning, the irregular menstrual cycles and potential of infertility, there are significant diseases that can result from the underlying syndrome, including an increased risk of cardiovascular disease, type II diabetes and uterine cancer.

The metabolic goals of a holistic natural medicine approach are to:

1. lower androgens
2. inhibit the conversion of testosterone to the more potent dihydrotestosterone
3. to induce regular ovulation, and
4. to modify insulin resistance and lower the hyper-secretion of insulin

Diet and exercise are common to both conventional and alternative treatments of PCOS-to promote weight loss, increase insulin sensitivity, decrease male hormone levels, and thus restoring ovulation. Dietary changes that may improve insulin resistance are the primary emphasis with a reduction of refined carbohydrates and total calories, while increasing the high fiber foods of vegetables, legumes and whole grains. Many individuals with PCOS will respond to a diet that is not more than 80 gm/day of carbohydrates, and 60-90 gm per day of protein.

There are several natural substances that bind to and stimulate sex hormone binding globulin (SHBG), which then binds some of the testosterone in our blood stream, which in turn reduces the hyperandrogenism of PCOS. The root of the nettles plant contains many lignans and these compounds have an affinity to SHBG in humans. Nettles root can also affect aromatase inhibition which could inhibit the conversion of the weaker testosterone to dihydrotestosterone.
Caffeine containing beverages (coffee, green tea, black teak, oolong tea and even colas), were seen to have a relationship between intake and increases in SHBG. This then, had a favorable effect on hormone levels,. As caffeine intake and SHBG increases, estrogen level decreases. This is just one of the mechanisms by which green tea may have breast health implications and favorably influencing the risk of breast cancer.

Flax seeds and soy, are two important foods groups relevant in a PCOS diet. The flax seeds again, containing lignans, which increases SHBG, lowering blood testosterone levels and perhaps reducing the hyperandrogenic effects.1 I recommend 1-2 tbsp per day of flax seeds or ground flax meal.

One of the potential significant aspects of PCOS is a buildup of the lining of the uterus. This occurs because the ovaries still produce adequate estrogen, but not enough progesterone, due to a lack of ovulation. The uterus then receives what is called unopposed estrogen stimulation. This thickening is called hyperplasia, and the cells over time can become atypical or even malignant. The potential role of soy foods in the diets of women with PCOS may have some contradictions but basically, it is thought that soy can reduce blood estrogen levels and increase SHBG and that women with higher soy diets excrete more than twice the amount of estrogen in their stool in one study, and increased the excretion of estrogens in the urine in another. There are indeed, other soy studies that do not show the same results. I recommend one to two servings of a soy food per day, or something equivalent to 50mg-100 mg of soy isoflavones daily.

Saw palmetto inhibits the activity of an enzyme, 5-alpha reductase, thereby reducing the conversion of testosterone to dihydrotestosterone, the more potent form. This may have implications in reducing acne, excess facial and body hair, as well as hair loss from the scalp. Saw palmetto was recently studied as part of a formula and was able to initiate a reduction in hair loss and an improvement in hair density in patients with testosterone related hair loss.

3.5 gms of a licorice root extract standardized to contain 7.6% W.W. glycyrrhizic acid (0.25 grams total glycyrrhizic acid per day), q.d. for 2 months was given to nine “healthy” women, ages 22-26 years. Outcome measures included blood pressure, plasma renin activity (PRA), plasma cortisol, plasma aldosterone, total serum testosterone, androstenedione, 17-OH-progesterone (17OHP) and gonadotropins, which were tested at baseline, after 1 and 2 months taking licorice, and one month post-treatment. Mean total serum testosterone significantly decreased after one and two months of treatment (27.8 ± 8.2 vs. 19. ± 9.4 and 17.5 ± 6.4 ng/dL, respectively).

It’s interesting to note that this is the first trial to follow-up on earlier trials that found that licorice may reduce testosterone secretion in women with polycystic ovary syndrome (Acta Obst Gynecol Jpn 1988;40:789-92) and another showing a similar result in hyperandrogenic and oligomenorrheic women.

Calcium and vitamin D are two of the most reaching nutrients our body needs affecting muscles, bones, thyroid, brain, heart, hormones, colon, breast and more. Calcium and vitamin D regulation may also contribute to the development of faulty ovarian follicle development in women with PCOS, resulting in reproductive and menstrual dysfunction. Vitamin D also plays a role in glucose metabolism and is commonly deficient in individuals with type 2 diabetes. Supplementing with vitamin D has been shown to improve glucose tolerance, insulin secretion and insulin sensitivity in those with DM., A deficiency of vitamin D may be more frequent in women with PCOS and in a small study, five of thirteen women had an overt vitamin D deficiency. Seven of the nine women with no menses or infrequent menses, had a return to a normal menstrual cycle within two months of being given 50,000 IU once or twice per week of vitamin D and 1,500 mg per day of calcium.10

Chromium is a trace mineral that enhances the action of insulin. Supplementing with chromium has been shown in some studies to improve the blood sugar control in those with type 2 DM. Giving PCOS women 1,000 mcg per day of chromium for as little as two months was able to improve insulin sensitivity by 30% and by 38% in obese women with PCOS.

A little known supplement, D-chiro-inositol is not commercially available, but pinitol, a compound similar to D-chiro-inositol, is available. Pinitol appears to mediate insulin activity. In an important study about this nutrient, 600 mg of pinitol twice per day for three months lowered blood glucose levels by 19%, lowered average glucose levels by 12% and significantly improved insulin resistance.

Conventional treatment of PCOS includes diet and exercise, and a drug, Metformin, used to improve insulin resistance. This can lead to normal ovulation. Other medications are used to induce ovulation such as clomiphene citrate, spironolactone to decrease testosterone on the hair follicle, and oral contraceptives to address irregular menstrual cycles and excess body hair. A topical medication, Vaniqa, is used topically, to reduce facial hair.

PCOS is a complicated condition, requiring long term attention and regular medical attention, keeping in mind the potential for increased risks of diabetes, hypertension, hyperlipidemia, uterine cancer.

As a practitioner with more awareness and experience with PCOS, we have an important role in detecting the long undiagnosed patient, the inadequately managed patient, and the discouraged patient.

In summary, a comprehensive plan for PCOS would include:

Weight loss in those who are overweight
Daily aerobic exercise one hour per day
Low simple carbohydrates (Up to 80 gm/day of carbohydrates and 60-90 gm per day of protein)
Flax seeds 1-2 tbsp per day
Soy food 1 to 2 servings per day
Vitamin D 2,000 i.u. per day or without testing, up to 5,000 i.u. per day
Calcium 1,000mg-1,500 mg per day (including dietary sources)
Chromium 1,000 mcg per day
Green tea (90% polyphenols, 80% catechins, 45% EGCG) 300mg-500 mg per day or 3 cups of tea per day
Nettles root 600 mg per day
Saw Palmetto extract 400 mg per day
Pinitol 600 mg twice per day

Consider Licorice root extract

Important resources:

Women’s Encyclopedia of Natural Medicine. Tori Hudson, N.D., McGraw/Hill publishing

PCOS, A Woman’s Guide to Dealing with Polycystic Ovary Syndrome. Colette Harris with Dr. Adam Carey. Thorson’s publishing

PCOS, The Hidden Epidemic. Samuel Thatcher, M.D., PhD. Perspectives Press

The Natural Diet Solution for PCOS and Infertility. Nan Dunne, N.D. (paperback and e-book

PCOS Health Review – free newsletter; Nan Dunne, N.D. and Bill Slater

References

• Schottner M, Gansser D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin. Planta Med 1997; 63(6): 529-532
• Gansser D, Spiteller G. Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts. Z Naturforsch 1995;50(1-2):98-104.
• Schottner M, GanBer D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG). Planta Med 1997; 63:529-532
• Gansser D, Spiteller G. Aromatase inhibitors from Urtica dioica roots. Planta Med. 1995;61(2): 138-140.
• Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese Women. Nutrition and Cancer 1998; 30(1): 21-24.
• Kumar N, Cantor A, Allen K, et al. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer 2002;94:1166-1174.
• Goldin B, Adlercreutz H, Gorbach S, et al. The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr 1986;44:945-953
• Xu X, Duncan A, Wangen K, Kurzer M. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiology, Biomarkers and Prevention 2000;9:781-786.
• Martini M, Dancisak B, Haggans C, Thomas W, Slavin J. Nutrition and Cancer 1999;34(2): 133-139.
• Prager N, Bicket K, French N, Marovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. JAH and Comple Med 2002;8(2): 143-152.
• Armanini D, et al. Steroids 2005;69:763-6.
• Acta Obst Gynecol Jpn 1982;34:939-44
• Thys-Jacobs S, Donovan D, Papadopoulos A, et al. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999;64:430-435.
• Raghuramulu N, Raghunath M, Chandra S, et al. Vitamin D improves oral glucose tolerance and insulin secretion in human diabetes. J Clin Biochem Butr 1992;13:45-51.
• Borissova A, Tankova T, Kirilov G, et al. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients, Int J Clin Pract 2003;57:258-261.
• Gaby A. Chromium. Integrative Med 2006;5(4):22-26.
• Lydic L, McNurlan M, Komaroff E, et al. Effects of chromium supplementation on insulin sensitivity and reproductive function in polycystic ovarian syndrome: a pilot study. Fertil Steril 2003;80 (Suppl 3): S45-S46.
• Lydic M, McNurlan M, Bembo S, Mitchell L, Komaroff E, Gelato M. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril 2006;86:243-246.
• Davis A, Christiansen M, Horowitz J, et al. Effect of pinitol treatment on insulin action in subjects with insulin resistance. Diabetes Care 2000;23:1000-1005.
• Kim J, Kim J, Kang M, et al. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus: a randomized contolled study. Eur J Clin Nutr 2005;59:456-458.

Fifty eight women were surgically diagnosed with endometriosis and were then started on Pycnogenol within 6 months of the surgery after confirming regular menstruation and ovulation for three months. Women were randomized to receive either pycnogenol 30 mg twice daily for 48 weeks or a gonadotropin-releasing hormone agonist (Gn-RHa), leuprorelin acetate depot, 3.75 mg IM six times every four weeks for 24 weeks. Patients were monitored at 4, 12, 24, and 48 weeks after treatment began.

Results: Both groups had similar symptoms before the treatments began: severe pain, pelvic tenderness and pelvic indurations. After four weeks on Pycnogenol, patients slowly but steadily improved reducing symptoms from severe to moderate. Overall, this group experienced a 33% reduction in symptoms of their endometriosis. The leuprorelin group had a greater response within the treatment period, but relapsed after 24 weeks post treatment. The Pycnogenol group maintained regular menses and normal estrogen levels during treatment and as expected, the leuprorelin group had suppressed menstruation and drastically lowered estrogen levels during treatment. In addition, five women in the trial taking Pycnogenol became pregnant.

Kohama T, Herai K, Inoue M. Effect of French maritime pine bark extract on endometriosis as compared with leuprorelin acetate. J Reprod Med 2007; 52(8):703-708.

Commentary: One of the most common causes of pelvic pain and infertility, endometriosis is a challenging problem for women and a complex problem to treat with natural medicine. New research shows multiple potential factors involved in the etiology and progression of the disease including:

• Retrograde menstruation
• Coelomic metaplasia
• Metastasis
• Iatrogenic
• Genetic
• Environmental factors
• Altered cellular immunity
• Increased inflammatory mediators

Issues of cellular metabolism and mitochondrial dysfunction are very important in women’s health, creating numerous problematic changes that result in hypothalamic suppression as well as dysfunctions in the brain, heart, skeletal muscles, liver and endocrine system. The hypothalamus controls sleep, pituitary and autonomic functions. When hypothalamic function is suppressed, it can result in insomnia, irritable bowel syndrome, deficiencies of growth hormone and hypothalamic-pituitary-adrenal and thyroid axis dysfunction. Chronic fatigue syndrome (CFS) and fibromyalgia (FMS) in particular, are common syndromes in women associated with decreased mitochondrial function and declining tissue levels of adenosine triphosphate (ATP).

Individuals with CFS/FMS are found to have: 20% less energy in their muscles,, defective or inefficient mitochondria, nutrient deficiencies in cells and tissues needed to process food into energy, and thickened capillary walls slowing the rate of synthesizing energy.

As cellular energy is depleted, fatigue and muscle pain become more and more severe and the muscles require additional energy in their recovery efforts. Energy is used faster than fuel is made available to renew it, and the fatigue, soreness, pain and stiffness continue to progress. Energy depletion reaches a critical point and CFS/FMS becomes a state in which the mechanisms for recovery are overwhelmed.

D-Ribose is a naturally occurring five-carbon sugar found in all living cells. It is the D-isomer of ribose that has been shown to possess biological activity. The body naturally converts glucose into ribose. Ribose is then used to drive the pathways of energy metabolism. One of the problems faced when the body’s ribose stores have been depleted, is that tissues such as heart and muscle are unable to produce it quickly enough to restore this depleted energy store. It is this delay that slows cellular and tissue energy recovery.

D-ribose is a component of ATP, RNA, NADH, and coenzyme-A, all needed by the mitochondria to maintain cellular energy homeostasis. In the body, we form ribose through the pentose phosphate pathway (PPP) or through the hexose monophosphate shunt. In heart and muscle tissue, the PPP is fairly slow because these tissues lack the enzymes needed to shunt the glucose in the pathway of ribose synthesis. These tissues instead prefer to use glucose to fuel ATP. The enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase preserve glucose metabolism, at a cost to ribose synthesis. When ribose is needed to rebuild the ATP pools, the process is slow. This is the main rationale for providing supplemental ribose for heart and muscle tissue, the purpose being to speed up the rebuilding of depleted ATP pools, thereby promoting a quicker more efficient tissue recovery.

Most body tissues cannot make enough ribose to restore energy levels to normal once they have been depleted. When cells suffer metabolic stress or mitochondrial dysfunction, ATP is catabolized and metabolic recovery is compromised. These mechanisms may be similar to what occurs in individuals with CFS. Under these conditions, adenosine diphosphate (ADP) accumulates and the cells try to balance the ratios of ATP with ADP to maintain energy. These reactions lead to catabolic end products that are washed out of the cell with a subsequent loss in purines and adenine nucleotides. One therapeutic option is to try to restore these energy substrates in order to recover the function of the cell, including muscle cells. By providing supplementation in the form of ribose, it is possible to enhance the nucleotide recovery, and preserve or even rebuild cellular energy stores.

D-ribose research in CFS/FMS was initiated with a case study in 2004 of a veterinary surgeon with fibromyalgia. After 3 weeks of ribose she was back to full time work, with her profound fatigue and muscle pain having disappeared. An important study was also done involving high-intensity athletes. Post exercise, muscle energy levels were reduced by almost 30%. Supplementing with 10 g of ribose per day for 3 days following the exercise restored muscle levels to normal while those treated with placebo received no effect.

An open-label uncontrolled pilot study was done to evaluate the effect of D-ribose on symptoms in forty-one CFS and FMS patients D-ribose was given at a dose of 5 grams t.i.d. for an average of three weeks. Questionnaires pre and post D-ribose intervention were compared and showed a significant improvement in five categories: energy, sleep, mental clarity, pain intensity and well being. At the end of the study, approximately 66% of patients experienced significant improvement while using D-ribose. These patients had a 45% average increase in energy and a 30% overall improvement in well-being.

Many individual nutrients and botanicals are utilized in the treatment of CFS/FMS: magnesium, CoQ10, malic acid, vitamin D, rhodiola, licorice, ginseng, resveratrol, carnitine and more. While most alternative minded practitioners embrace a whole system, mind/body, functional approach in working with these challenging clinical situations, I have found D-ribose to be the single most important nutrient in the search for alleviation of symptoms and a path towards health. I thank Jacob Teitelbaum, M.D. and other D-ribose researchers for pointing us in the right direction.

References

• No authors listed. Symptoms of mitochondrial cytopathies. United Mitochondrial Disease Foundation. Avalable at http://www.umdf.org/site/c.dnJEKLNqFoG/b.3042207/. Accessed March 4, 2008.
• Mignot E, Taheri S, Nishino S. Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Nat Neurosci 2002; Nov;5 Suppl: 1071-1075.
• Palkovits M. Interconnections between the neuroendocrine hypothalamus and the central autonomic system. Geoffrey Harris Memorial Lecture, Kitakyushu, Japan, October 1998. Front Neuroendocrinol. 1999;20(4):270-295.
• Demitrack M, Dale K, Straus S, et al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. 1991: 73(6); 1223-1234.
• Bengtsson A, Henriksson K. The muscle in fibromyalgia-a review of Swedish studies. J Rheumatol Suppl. 1989 Nov; 19:144-149.
• Lund N, Bengtsson A, Thjorborg P. Muscle tissue oxygen pressure in primary fibromyalgia. Scand J Rheumatol. 1986; 15(2):165-173.
• Strobel E, Krapf M, Suckfull M, et al. Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia. Rheumatol Int. 1997; 16(5)175-180.
• Douche-Aourik F, Berlier W, Feasson L, et al. Detection of enterovirus in human skeletal muscle from patients with inflammatory muscle disease or fibromyalgia and healthy subjects. J Med Virol. 2003;71(4):540-547.
• Park J, Phothimat P, Oates C, Hernanz-Schulman M, Olson N. Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum. 1998; 41(3):406-413.
• Kushmerick M. Muscle energy metabolism, nuclear magnetic resonance spectroscopy and their potential in the study of fibromyalgia. J Rheumatol Suppl. 1989 Nov; 19:40-46.
• Bengtsson A, Henriksson K, Larsson J. Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia. Arthritis Rheum. 1986;29(7):817-821.
• Lund E, Kendall S, Janerot-Sjoberg B, Bengtsson A. Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise. Scand J Rheumatol. 2003;32(3):138-145.
• Eisinger J, Bagneres D, Arroyo P, Plantamura A, Ayavou T. Effects of magnesium, high-energy phosphates, piracetam and thiamin on erythrocyte transketolase. Magnes Res. 1994;7(1):59-61.
• Pouleur H. Diastolic dysfunction and myocardial energetics. Eur Heart J 1990; 11(Supp): 30-34.
• Pasque M, Wechsler A. Metabolic intervention to affect myocardial recovery following ischemia. Ann Surg 1984;200:1-10.
• Perlmutter N, Wilson R, Angello D, et al. Ribose facilitates thallium-201 redistribution in patients with coronary artery disease. J Nucl Med 1991; 32:193-200.
• Gebhart B, Jorgenson J. Benefit of ribose in a patient with fibromyalgia. Pharmacotherapy. 2004;24(11):1646-1648.
• Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol. 2004;286(1):R182-R188.
• Teitelbaum J, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med 2006 Nov; 12(9):857-862.

The purpose of this study was to evaluate the effects of Pycnogenol in reducing symptoms of osteoarthritis (OA) in a double-blind, placebo-controlled, randomized trial. 100 patients older than age 25 (14 men and 36 women in the pycnogenol group and 18 men and 32 women in the placebo group) suffering from mild OA (stage I or II) in at least one knee and mild to moderate pain for at least 3 months prior to the study, and/or morning knee stiffness and /or knee crepitus.

The main outcome criteria were reduction of symptoms of OA using WOMAC scores and reduction of pain using visual analogue scale (VAS). The secondary outcome was a decrease in the use of analgesics. Study subjects were randomly assigned to Pycnogenol 50 mg tid or placebo. Patients were allowed to continue with their medication with NSAIDs or analgesics if they were using them before the start of the study and were allowed to change medication as needed but then reported dosage or frequency changes at each visit. Patients were evaluated at baseline, at 3 months and 4 weeks after completing the treatment. The WOMAC questionnaire for pain, stiffness and daily activities was completed by the patient every 2 weeks during the whole study. The VAS for pain was filled in by each patient weekly during the whole study.

Results: The WOMAC-A score, summarizing pain scores, improved significantly in the Pycnogenol group (p=00004) over the time of the study. The statistical difference for pain reduction compared to baseline in the Pycogenol group was evident after weeks 8,12 and 14 (p < 0.001). The difference between treatment group and placebo was near statistical significant at week 8 (p= 0.08).

The WOMAC-B score, the stiffness score, improved statistically significant (p=0.01) in the Pycnogenol groups versus baselines after weeks 8,12 and 14. Statistically significant differences between treatment group and placebo group were observe at weeks 8 and 12 (p< 0.05).

The WOMAC score in regards to the ability to perform daily activities improved significantly versus baseline in the Pycnogenol group at weeks 8,12 and 14 (p< 0.01). The change in the placebo group was not significant and the difference between the Pycnogenol and placebo groups was not significant.

Pain scores by VAS was somewhat higher in the placebo group than the Pycnogenol group at baseline although not significant. After treatment for 4 weeks, the treatment group reported less pain when compared to the placebo and pain continued to diminish until month 3. The correlation of decreased pain over time was statistically significant (p< 0.04) for the Pycnogenol group, but the correlation was poor for the placebo group (p<0.17). Only a marginal significance was seen between Pycnogenol versus placebo was seen at weeks 4 ( p=0.08) and 8 (p=0.07).

Patients in the Pycnogenol group were able to reduce their use of analgesics or NSAIDs at a higher percentage than those in the placebo group and 10% of placebo group patients had to increase their dose of analgesics whereas no higher doses were needed in the Pycnogenol group.

Cisar P, Jany R, Waczulikova I, et al. Effect of Pine Bark Extract (Pycnogenol) on symptoms of knee osteoarthritis. Phytotherapy Research 2008;22:1087-1092

Commentary: I’m encouraged to see this study and am looking forward to using this in patients with milder to moderate OA symptoms, especially of the knees. Pycnogenol is a special standardized extract from the bark of the French maritime pine. It is composed of polyphenols, several phenolic acids, catechins, taxifolin and procyanidins. In laboratory research Pycnogenol selectively inhibits matrix metalloproteinases (MMPs). MMPs are one of the inflammatory responses in arthritic joints induced by interleukin-1. The matrix degrading activity contributes to the loss of cartilage and is associated with chronic inflammation. Other in nvitro research has shown that Pycnogenol inhibits other inflammatory cells and specifically inhibits COX1 and COX2. These previously observed anti-inflammatory effects as a background to the current study, contributes a body of information that enables us to have another viable alternative treatment in early OA of the knee as well as an approach to possibly reduce the use of analgesics and NSAIDs in pain management.

As the saying goes, you usually get what you pay for. But just so you know what you’re paying for, multivitamin-mineral supplements vary in four basic ways:

1. ingredients
2. potency
3. quality
4. manufacturing process

In general, however, basic mass-market multiples are often sold at a lower price because they are inferior in one or more of those four basic ways. Typically, they omit mixed carotenoids, bioflavonoids and smaller minerals and nutrients such as vitamin K, boron and iodine. Because they contain fewer ingredients, and often not some of the premier more costly ingredients such as CoQ10, they are less expensive. One of the most striking differences is the amount of individual ingredients. For instance, vitamin D may range from 100 IU to 400 IU; calcium may vary from 200 mg to 500 mg. Taking one capsule/tablet per day may be what is written on the label, but serving sizes may be 2 or 3 capsules in order to get the total on the label. The point is, read the label carefully so you are taking the number of capsules you need to take, in order to get the dose on the label. Many of the vitamins and minerals are available in more than one form and some are more bioavailable than others. Bioavailability is determined by absorption or more efficient use by the body. For instance, calcium carbonate is usually less expensive, but for some people it is constipating and they do better with calcium citrate - this is not necessarily more expensive, but it is a bulkier form of calcium with less elemental calcium per pill, so you have to take more pills to get the dose you have targeted. Many vitamins are synthetic and aren’t available in natural forms. Beta carotene for example comes in a natural or synthetic form and better yet, some multiples contain natural mixed carotenoids and the natural form of other vitamins, which provide additional more potent antioxidant effects. Processing methods also vary, and some of those methods expose the nutrients to greater heat less stable conditions, and use additives and dyes which can render them with less nutritional value.

One capsule/tablet per day mass market multis are usually very low potency, contain the less desired form of the nutrient, omit some important ingredients that would be optimal for a daily vitamin, and contain unnecessary additives. Look for multis where the serving size is 2 or 3 capsules per day, have mixed natural carotenoids, have some of the extras such as bioflavonoids, vitamin K, boron, iodine and then you have to be a bit studious in order to learn about the more bio-available forms of nutrients. The book, Encyclopedia of Nutritional Supplements by Michael Murray, N.D. is an excellent resource for this.

Thirty-two hirsute women with polycystic ovary syndrome (PCOS) were studied in an open-label clinical trial. All the women were given 100 mg of spironolactone per day while sixteen of them also received 3.5 g/day of a licorice root extract standardized to 7.6% glycyrrhetinic acid. Study duration was two months. Systolic blood pressure significantly decreasd at 30 and 60 days in the women taking spironolactone (SP), but not in the SP plus licorice group. Diastolic blood pressure did not change in either group. Twenty percent of the women in the SP only group had fatigue, orthostatic symptoms and polyuria. These were most significant in the first two weeks of treatment but diminished over the course of the study. Women in the SP and licorice group did not report any of these side effects. Plasma rennin activity and aldosterone were more increased in the SP only group compared with the other group. There were no changes in SHBG in either the SP only group or the SP plus licorice. Plasma cortisol increased in both groups after 30 and 60 days.

Armanini D, Castello R. Scaroni C, et al. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur J Obstet Gynecol 2007;131:61-67.

Commentary: It’s very useful to find a second study on licorice and it’s role in PCOS. Glycyrrhetinic acid has been shown to reduce serum testosterone and induce regular ovulation. (Yaginuma T, Izumi R, Yasui H, et al. Effect of traditional herbal medicine on serum testosterone levels and its inductions of regular ovulation in hyperandrogenic and oligomenorrheic women. Nippon Sanka Fujinka Gakkai Zasshi 1982;34:939-944) ( Takahashi K, Yoshino K, Shirai T, et al. Effect of a traditional herbal medicine on testosterone secretion in patients with polycystic ovary syndrome detected by ultrasound. Nippon Sanka Fujinka Gakkai Zasshi 1988;789-92.)

Spironolactone is often used as part of a treatment plan in PCOS women with bothersome hirsutism. While Spironolactone can be helpful, fatigue and polyuria are a frequent side effect. It may be that licorice and glycyrrhetinic acid have a potential synergistic effect on the androgen receptors, reduce the side effects associated with Spironolactone, as well as reducing serum testosterone and inducing regular ovulation. Licorice extract along with a lower carbohydrate/higher protein diet, therapies that increase SHBG such as nettles root, green tea, flax seeds and soy and insulin sensitizing strategies such as daily aerobic exercise, fenugreek powder, cinnamon extract, d-pinitol, chromium (and possibly glucophage) offer a comprehensive approach for women with PCOS.

In order to evaluate the efficacy of a topical green tea extract, researchers conducted a randomized, double-blind, vehicle (placebo)-controlled trial involving 502 men and women aged 18 and older. Participants were clinically diagnosed with 2 to 30 external genital and perianal warts and were randomly assigned to receive sinecatechins ointment 15%, sinecatechins ointment 10% or vehicle (placebo). The duration of treatment was a maximum of 16 weeks or until there was complete clearance of all baseline and new warts, whichever occurred first, followed by a 12 week treatment free phase at which time wart recurrence was assessed.

Seven patients were excluded from analysis and the results were based on 495 patients (254 men and 241 women). Baseline warts were mainly on the vulva (41.2% of women), and penile shaft (36.9% men), followed by the perianal area (18.1% total), perineal area (15.3% total) and glans penis (11.8% men).

Complete clearance of all baseline and newly occurring warts occurred in 57.2% and 56.3% of patients treated with both 15% and 10% sinecatechins ointment compared with 33.7% for the vehicle (both P < .001). Significant results were observed at week 4 and 6 and all follow-up visits. Partial responses of at least 50% occurred in 78.4% of the 15% ointment group, 74.0% of the 10% ointment group, and 51.5% in the vehicle group. The recurrence on any wart occurred in 6.5% of the patients using the 15% ointment, 8.3% with the 10% ointment and 8.8% using the vehicle. There was also a very low rate of new warts at the end of the treatment in all groups.

Tatti S, Swinehart J, Thielert C, et al. Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts. ObGyn 2008;111:1371-1379.

Commentary: External genital warts are one of the most common sexually transmitted infections, yet no single treatment has emerged as delivering the best outcomes. Options include herbal topical applications of thuja, licorice root and vitamin A, homeopathic medicines, and conventional treatments including podofilox solution or gels, imiquimod cream, trichloroacetic acid, cryotherapy, curettage, electrosurgery, excision, laser therapy, interferon and 5-fluorouracil gel.

This study is one of two independent phase III studies to establish efficacy and safety of sinecatechins ointment. Overall, patients in both the 15% and 10% ointment group had a significantly higher number of complete clearances of baseline warts and a lower number of recurrent lesions during the 12 week treatment free follow-up period. The results were better in women than in men, likely due to the greater keratinization of the skin on the penile shaft. Based on clearance rates of all warts, a 50% success was achieved in almost 80% of patients in both sinecatechins ointment strengths. Recurrence rates are higher in cryotherapy, imiquimod and podofilox. The results of the current study indicate that a green tea extract ointment standardized to 15% or 10% sinecatechins is a very effective topical treatment to clear warts, inhibit new external anogenital warts and keep patients wart free.

The objective of this double-blind, placebo-controlled trail was to study whether saffron could be used to relieve PMS symptoms. 50 reproductive aged women with regular menstrual cycles and with PMS symptoms for at least the last 6 months were randomly assigned to receive 15 mg of saffron twice daily, or placebo twice daily, for four full menstrual cycles. The Daily Symptom Report and the Hamilton Depression Rating Scale were used to evaluate the response.According the Daily Symptom Report 19 of the 25 women in the saffron group responded with at least a 50% reduction in severity of symptoms, vs only 2 of 25 in the placebo group (P< 0.0001). A significant difference between the saffron group and placebo group occurred between the third and four cycle and was statistically significant by the end of the study (P< 0.0001).

According the Hamilton Depression Rating Scale, 15 of 25 women in the saffron group responded to treatment vs only 1 of 25 in the placebo group. (P< 0.0001). Again, a significant difference was seen between cycles 3 and 4 with a statistically significant difference by the study end (P< 0.0001).

Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Agha-Hosseini M, Kashani L, Aleyaseen A, et al. BJOG 2008;115:515-519.

Commentary: Improvements in the Total Premenstrual Daily Symptoms and the Hamilton Depression Rating Scale with saffron should give us definite motivation to try this simple treatment. Saffron has been previously shown to have an antidepressant effect in women with mild to moderate depression, through a serotonergic mechanism, so it’s not surprising that it would work in PMS. Research on PMS in the last several years has pointed strongly to the etiology being the dysregulation of the serotonergic system. This is why we have seen conventional medical practitioners focus on the use of SSRIs in treatment.

This is the first clinical trial I’ve seen in the use of saffron for the treatment of PMS. While only a small study and short follow-up, the positive results warrant further study, and in the meantime, accumulating some clinical experience.