CoEnzyme Q10

Overview

Coenzyme Q10, or CoQ10, is found in the mitochondria of all cells and is particularly enriched in tissues of the heart, liver, kidney and pancreas. CoQ10 functions as part of the cellular system that generates energy from oxygen (in the form of ATP) for bodily processes. CoQ10 can also act as an antioxidant to help prevent cellular damage from free radicals created during exercise and during the generation of energy.

Dietary supplements containing CoQ10 (often suspended in soybean oil or other oil base for better absorption) are generally marketed with claims of increasing energy and endurance levels, supporting heart function, reducing blood pressure, and improving overall heart strength.

Because coenzyme Q10 is part of the respiratory chain as an electron/proton carrier, it functions in the production of adenosine triphosphate (ATP) in the mitochondria of the cell. CoQ10 has also been shown to exhibit activity as a free radical scavenger and antioxidant. The theory of CoQ10 supplementation posits that consumption of CoQ10 increases tissue and mitochondrial CoQ10 levels and supports ATP production as well as serving an antioxidant function.

Comments

For athletes, the data do not consistently support the use of supplemental CoQ10 as an ergogenic performance aid. As a general “energetic” dietary supplement, as in the case of reducing fatigue and alleviating symptoms of Chronic Fatigue Syndrome, the effectiveness of CoQ10 supplementation is largely unsupported. As an antioxidant, especially in combination with other antioxidants such as vitamins C and E, CoQ10 appears to be beneficial. For heart patients, CoQ10 appears to be especially indicated, particularly in those patients who may be taking cholesterol-lowering medications (HMG-CoA reductase inhibitors in the class of “statin” medications that includes lovastatin (Mevacor) simvastatin (Zocor), pravastatin (Pravachol), and fluvastatin (Lescol)).

Scientific Support

Since CoQ10 levels peak around age 20 and decline with age, it seems logical that supplemental CoQ10 might be beneficial in older adults. The antioxidant effects of CoQ10 are well-established. A number of studies have shown that CoQ10 reduces the initiation and propagation of lipid peroxidation (free radical damage) in cell membranes and in lipoprotein fractions (Taggart et al. 1996). Additionally, combined supplementation of CoQ10 plus vitamin E produces a synergistic antioxidant effect on lipoproteins and "spares" the vitamin E (Kucharska et al. 1996).

In heart disease, CoQ10 has shown benefits in patients with heart failure – with 50mg daily for 4 weeks resulting in improvements in dyspnea, heart rate, blood pressure, and ankle edema (Hoffman-Bang et al. 1995). In most studies of heart failure, a significant reduction in hospitalizations and episodes of pulmonary edema and cardiac asthma are generally observed (Khatta et al. 2000). Cardiac patients supplemented with CoQ10 prior to heart surgery tend to recover sooner and maintain blood and tissue levels of CoQ10 better than patients not receiving supplements. In a one study, 144 patients suffering from acute MI benefited from 28 days of CoQ10 at 120mg/day when compared to placebo by decreasing incidence of angina, arrhythmias, and poor left ventricular function (Soja et al. 1997). A handful of studies have suggested reductions in systolic and diastolic blood pressure of 7-10mmHg after 8-10 weeks of CoQ10 supplementation (Sacher et al. 1998, Singh et al. 1998). In addition, individuals taking cholesterol-lowering medications (HMG-CoA reductase inhibitors – also known as “statin” drugs) may benefit from CoQ10 supplements because these medications can reduce blood levels of CoQ10 (Langosjoen and Langosjoen 1999). In several studies, CoQ10 levels have been shown to be significantly reduced with simvastatin and related statin medications, resulting in an accompanying reduction in ejection fraction response to exercise, myocardial reserve, and myocardial contractile function (Langosjoen and Langosjoen 1999, Knontush et al. 1997). CoQ10 was approved in 1974 in Japan for the treatment of congestive heart failure and at least one formulation (UbiQGel), has received FDA Orphan Drug Status for treating mitochondrial disorders (Greenberg and Frishman 1990).

The one area in which data is most conflicting is for CoQ10 as an ergogenic aid for athletic performance. Because of its role in ATP synthesis, it is logical that supplemental CoQ10 may support the process of cellular energy production. Research in this area has been conflicting, however, with some studies showing a benefit and others showing no effect (Weston et al. 1997).

Safety/Dosage

CoQ10 has a good safety profile and daily doses of 50-100mg are well tolerated. Reported side effects are rare, but tend to be various forms of epigastric distress (heartburn, nausea, stomachache) which can be prevented by consuming the supplement with a meal. Intakes of 100-200mg per day have been studied with no apparent adverse side effects, but muscle damage has been noted in at least one study (Kucharska et al. 1998) of 120mg per day over 20 days (perhaps due to a pro-oxidant effect and free radical damage in the muscle).

Smoking is known to deplete CoQ10 levels in blood and tissues. Several medications can reduce blood and tissue levels of CoQ10, including those for controlling cholesterol (statins, including a theoretical reduction in CoQ10 levels with use of red yeast rice supplements, which contain natural lovastatin), blood pressure (beta-blockers, by inhibiting CoQ10-dependent enzymes), and blood sugar (some oral hypoglycemic agents), suggesting that CoQ10 supplements may be warranted in patients taking these medications. HMG-CoA reductase inhibitors can reduce CoQ10 concentrations by approximately 32 to 47% by blocking the synthesis of mevalonic acid, a precursor of coenzyme Q-10.

References

1.Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990 Jul;30(7):596-608.

2.Gvozdjakova A, Kucharska J, Mizera S, Braunova Z, Schreinerova Z, Schramekova E, Pechan I, Fabian J. Coenzyme Q10 depletion and mitochondrial energy disturbances in rejection development in patients after heart transplantation. Biofactors. 1999;9(2-4):301-6.

3.Hofman-Bang C, Rehnqvist N, Swedberg K, Wiklund I, Astrom H. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group. J Card Fail. 1995 Mar;1(2):101-7.

4.Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R, Robinson SW, Gottlieb SS. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med. 2000 Apr 18;132(8):636-40.

5.Kontush A, Reich A, Baum K, Spranger T, Finckh B, Kohlschutter A, Beisiegel U. Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia. Atherosclerosis. 1997 Feb 28;129(1):119-26.

6.Kucharska J, Gvozdjakova A, Mizera S, Braunova Z, Schreinerova Z, Schramekova E, Pechan I, Fabian J. Participation of coenzyme Q10 in the rejection development of the transplanted heart: a clinical study. Physiol Res. 1998;47(6):399-404.

7.Kucharska J, Gvozdjakova A, Mizera S, Margitfalvi P, Schreinerova Z, Schramekova E, Solcanska K, Notova P, Pechan I, Fabian J. Coenzyme Q10 and alpha-tocopherol in patients after heart transplantation. Bratisl Lek Listy. 1996 Oct;97(10):603-6.

8.Langsjoen PH, Langsjoen A, Willis R, Folkers K. Treatment of hypertrophic cardiomyopathy with coenzyme Q10. Mol Aspects Med. 1997;18 Suppl:S145-51.

9.Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in cardiovascular disease. Biofactors. 1999;9(2-4):273-84.

10.Mortensen SA. Coenzyme Q10 as an adjunctive therapy in patients with congestive heart failure. J Am Coll Cardiol. 2000 Jul;36(1):304-5.

11.Munkholm H, Hansen HH, Rasmussen K. Coenzyme Q10 treatment in serious heart failure. Biofactors. 1999;9(2-4):285-9.

12.Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S. Coenzyme Q10 in health and disease. Eur J Clin Nutr. 1999 Oct;53(10):764-70.

13.Sacher HL, Sacher ML, Landau SW, Kersten R, Dooley F, Sacher A, Sacher M, Dietrick K, Ichkhan K. The clinical and hemodynamic effects of coenzyme Q10 in congestive cardiomyopathy. Am J Ther. 1997 Feb-Mar;4(2-3):66-72.

14.Sinatra ST. Coenzyme Q10: a vital therapeutic nutrient for the heart with special application in congestive heart failure. Conn Med. 1997 Nov;61(11):707-11.

15.Sinatra ST. Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration. Mol Aspects Med. 1997;18 Suppl:S299-305.

16.Singh RB, Wander GS, Rastogi A, Shukla PK, Mittal A, Sharma JP, Mehrotra SK, Kapoor R, Chopra RK. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998 Sep;12(4):347-53.

17.Soja AM, Mortensen SA. Treatment of chronic cardiac insufficiency with coenzyme Q10, results of meta-analysis in controlled clinical trials. Ugeskr Laeger. 1997 Dec 1;159(49):7302-8.

18.Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials. Mol Aspects Med. 1997;18 Suppl:S159-68.

19.Taggart DP, Jenkins M, Hooper J, Hadjinikolas L, Kemp M, Hue D, Bennett G. Effects of short-term supplementation with coenzyme Q10 on myocardial protection during cardiac operations. Ann Thorac Surg. 1996 Mar;61(3):829-33.

20.Weston SB, Zhou S, Weatherby RP, Robson SJ. Does exogenous coenzyme Q10 affect aerobic capacity in endurance athletes? Int J Sport Nutr. 1997 Sep;7(3):197-206.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Hawthorn

Overview

Hawthorn is an English shrub that has a long history of medicinal use in herbal medicine, including cardiovascular disorders, digestive complaints, dyspnea and kidney stones. Hawthorn is a popular phytomedicine in Europe for use in cardiovascular disorders today. Hawthorn has the ability to increase the integrity of the blood vessel walls, improving coronary blood flow, improve oxygen utilization, and to possess positive inotropic activity. The cardiovascular effects of hawthorn are thought to be the result of these activities and primarily due to the flavonoid group of compounds present in hawthorn. Clinical trials conducted on congestive heart failure (functional class II) patients have shown good results, including positive implications on the changing of blood lipids (Rigelsky and Sweet, 2002).

Comments

In Europe hawthorn is a widely used phytotherapy used alone and in combination with digitalis for congestive heart failure. As clinical evidence continues to mount in the favor of the use of hawthorn as a cardioprotectant, its popularity in the United States is also increasing.

Scientific Support

Blood Pressure Reduction

Hawthorn extract was tested singly and in combination with magnesium supplements and compared to placebo for its ability to lower blood pressure. Thirty-six mildly hypertensive people were involved in the study and randomly assigned to undergo a 10-week supplementation regimen of either: a) 600 mg of Magnesium, b) 500 mg of hawthorn extract, c) the combination of the two (a and b), or d) placebo. A decline in the systolic and diastolic blood pressure was found in all treatment groups, with no difference found between the groups. Factorial contrast analysis in ANOVA found a reduction in resting diastolic blood pressure at the end of treatment in 19 of the subjects given hawthorn extract, along with a trend in the reduction of anxiety in this group. The authors noted the low dose of hawthorn extract used in the study and thought the results prompted further study for hawthorn (Walker et al., 2002).

Cardiovascular Disease

Pittler et al (2003) conducted a meta-analysis on the studies with hawthorn used to treat chronic heart failure. A variety of database searches were performed and experts commercial manufacturers in the field were asked to contribute published and unpublished studies. Inclusion criteria of randomized, double-blind, placebo controlled studies with hawthorn used alone in therapy resulted in 13 trials. Eight of these trials that involved 632 patients met the meta-analysis criteria. Improvement of outcome measures of workload and pressure-heart rate were found in the hawthorn groups. Symptoms that showed improvement from hawthorn treatment included dyspnea and fatigue. Infrequent, mild and transient side effects of nausea, dizziness, and cardiac and gastrointestinal complaints were found. The authors concluded that hawthorn extract proved to be a beneficial adjuvunct therapy for NYHA class II cardiac disease.

Hawthorn extract (standardized extract of the fresh berries of C. oxyacantha and C. monogyna) was tested in a placebo controlled, randomized, parallel multicenter clinical study in patients with NYHA class II cardiac failure. The 143 participants were given either hawthorn extract (30 drops three times daily) or placebo for 8 weeks. Primary outcome measurements were the changes in exercise tolerance (bicycle exercise tolerance testing), and secondarily, blood presure-heart rate product (BHP). In the hawthorn treatment group there was a significant improvement found, with dyspnoea and fatigue not occuring until a significanly higher wattage of bicycle output had been reached. The authors concluded that NYHA II patients undergoing long term hawthorn therapy could expect improvement in their condition (Degenring et al., 2003).

Hawthorn extract (Rob 10) was tested on exercise tolerance and quality of life in 88 patients in a placebo-controlled, randomized, double-blind clinical study. Patients were given 25 drops, three times daily of the hawthorn extract or placebo for three months. Treatment with hawthorn resulted in a significant increase in exercise time, and beneficially impacted the quality of life assessment, the assessments of dyspnea. The authors concluded that hawthorn extract was able to be used safely and efficaciously in NYHA type II congestive heart failure patients (Rietbrock et al., 2001).

Hawthorn extract (WS 1442-standardized to 18.72% oligomeric procyanidines) was tested in 40 NYHA class II pateints in a randomized, placebo-controlled, double-blind clinical study. Patients were treated with either hawthorn extract (1 capsule three times daily) or placebo for 12 weeks. The primary outcome in this study was the effect on exercise tolerance, and as a secondary outcome the blood pressure-heart rate product was calculated. The treatment group produced a borderline significant improvement in exercise tolerance, and a significant improvement in the blood pressure-heart rate product. Administration of hawthorn extract was found to be safe and well tolerated, and effective for NYHA class II heart failure (Zapfe jun, 2001).

A standardized hawthorn extract (WS 1442) was tested in a multicenter utilization observational study. Hawthorn (Crataegutt novo 450, 1 tablet b.i.d) was administered to 1,011 patients with NYHA type II cardiac insufficiency over 24 weeks. Hawthorn extract administration resulted in a significnat improvement in the clinical symptoms of NYHA II, including reduced exercise tolerance, fatigue, palpitation and exercise dyspnea. Additionally, ankle edema and nocturia was reduced by 83% in half of the patients with these symptoms before treatment. Exercise tolerance was found to be increased overall, as well as a reduction in blood pressure, blood pressure-heart rate product (BHP), a stabilization in the heart rate, improvement in measures of myocardial perfusion, and the overall assessments of improvement by the patient and the physician were found from hawthorn treatment. The authors concluded hawthorn extract to be an efficient, well-tolerated and easily regulated therapeutic alternative for NYHA II patients (Tauchert et al., 1999).

Leuchtgens (1993) studied hawthorn extract (WS 1442) in NYHA II cardiac insufficiency patients in a placebo-controlled, randomized, double-blind study. Hawthorn was administered (1 capsule two times daily) for 8 weeks or placebo, and the blood pressure-heart rate product (BHP) and a subjective assessment of improvement were used as primary outcomes, and exercise tolerance, change in heart rate, and arterial blood pressure were used as secondary outcomes. Hawthorn treatment produced a statistically significant improvement in the measures of BHP, subjective assessments of improvement, and also in the heart rates. Both groups produced a mild reduction in systolic and diastolic blood pressure and no adverse reactions were observed.

Safety / Dosage

Generally, the recommended dosage level for hawthorn is 160-900 mg of a water-ethanol extract (equivalent to 30-169 mg epicatechin or 3.5-19.8 mg flavonoids) 2-3 times daily (Rigelsky and Sweet, 2002).

Side effects of hawthorn are usually mild and transitory, but may include a mild rash, headache, sweating, dissiness, palpitations, sleepiness, agitation and gastrointestinal upset. Drug interactions may occur with other vasodilators, it is thought to potentially potentiate or interact with other drugs used for heart failure, hypertension, angina and arrhythmias (Rigelsky and Sweet, 2002). A recent randomized crossover clinical study was conducted in order to determine the potential interaction with drugs that are P-sglycoprotein substrates, such as digoxin. The authors concluded that in the dosages studied (450 mg two times daily of Hawthorn leaves and flowers extract, and 0.25 mg digoxin), the two medications could be coadministered safely (Tankanow et al., 2003).

References

1.Degenring FH, Suter A, Weber M, Saller R. A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine. 2003;10(5):363-9.

2.Leuchtgens H. [Crataegus Special Extract WS 1442 in NYHA II heart failure. A placebo controlled randomized double-blind study] Fortschr Med. 1993 Jul 20;111(20-21):352-4.

3.Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med. 2003 Jun 1;114(8):665-74.

4.Rigelsky JM, Sweet BV. Hawthorn: pharmacology and therapeutic uses.

5.Am J Health Syst Pharm. 2002 Mar 1;59(5):417-22.

6.Rietbrock N, Hamel M, Hempel B, Mitrovic V, Schmidt T, Wolf GK. [Actions of standardized extracts of Crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure] Arzneimittelforschung. 2001 Oct;51(10):793-8.

7.Tankanow R, Tamer HR, Streetman DS, Smith SG, Welton JL, Annesley T, Aaronson KD, Bleske BE. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). J Clin Pharmacol. 2003 Jun;43(6):637-42.

8.Tauchert M, Gildor A, Lipinski J. [High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure] Herz. 1999 Oct;24(6):465-74; discussion 475.

9.Walker AF, Marakis G, Morris AP, Robinson PA. Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension. Phytother Res. 2002 Feb;16(1):48-54.

10.Zapfe jun G. Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA class II. Phytomedicine. 2001 Jul;8(4):262-6.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Cat's Claw

Overview

Although Cat’s Claw (or “una de gato”) is generally thought of as only coming from the rainforests of Peru, it is also found in the rainforests of surrounding countries such as Brasil and Bolivia. It has numerous traditional medicine uses, along with the popular uses today of immune system stimulation/modulation. It is known to possess antioxidant and anti-inflammatory activity, and has been used for numerous illnesses such as cancer, AIDS, colds/flu, yeast infections, intestinal/gastric ulcers and both osteo- and rheumatoid arthritis.

Comments

A lively debate exists for which chemotype (eg. containing pentacyclic or tetracyclic oxindole alkaloids) of cat’s claw and which species “is the best”. A recent preclinical study using in vitro methods by Sandoval et al (2002) concluded that although both species show antioxidant and anti-inflammatory effects, the presence of oxindole or pentacyclic alkaloids did not influence these activities. Sandoval et al (2002) further concluded that U.guianensis is more potent in these activities. Saventaro is the brand name of a cat’s claw extract that contains the pentacyclic oxindole alkaloids (manufactured by an Austrian company, Immodal Pharmaka).

Another debate exists as to which part of the plant is the most efficacious. Although many references have been made to the use of the root bark traditionally, today the stem bark is more popular, mostly due to its availability and higher sustainability of harvest.

Recent animal studies on a proprietary extract of cat’s claw called C-Med 100 have found that it has the ability to increase spleen cell numbers dose-dependently, but the effect was not due to increasing proliferation rate but rather their survival rate. Thus the authors noted the possible use of this extract for patients with leukopenia (Akesson et al., 2003).

Scientific Support

Rheumatoid Arthritis

An extract of the pentacyclic chemotype of U. tomentosa was studied in 40 rheumatoid arthritis patients (also taking sulfasalazine or hydroxychloroquine) for its safety and efficacy. The study design was a 52-week 2-phase study, with the first phase consisting of 24 weeks and being double-blind and placebo-controlled, and the second phase consisting of 28 weeks with all patients taking the cat’s claw treatment. In the first phase of the study the treatment group showed a statistically significant reduction in number of painful joints compared to the placebo group. In the second phase of the study, treatment resulted in a reduction in the number of painful and swollen joints, and in the Ritchie Index compared to the post-treatment values. Minor side effects were observed and the treatment was concluded to be relatively safe and of modest benefit (Mur et al., 2002).

Osteoarthritis

Cat’s claw was studied for its effect in patients with osteoarthritis of the knee, safety and for its in-vitro antioxidant and anti-inflammatory actions. In 45 patients with osteoarthritis of the knee, freeze-dried U.guianensis was given to 30 and placebo to 15, and hematological parameters were studied. No negative effects were found on the blood, liver, or experienced side effects compared to placebo. Symptoms that were significantly reduced by treatment were pain associated with activity and medical and patient assessment scores. However, no changes were found in knee pain at rest, at night, and knee circumference. In vitro studies of antioxidant (using the DPPH free radical scavenging method) and anti-inflammatory (measuring TNFalpha, and PGE2 production) activity showed both species to be equally efficacious. Due to the dosages studied, it was hypothesized that anti-inflammatory activity may result more from ability to inhibit TNFalpha rather than PGE2 (Piscoya et al, 2001).

The proprietary cat’s claw extract called C-MED 100 was studied for its ability to affect the response to 23 valent pneumococcal vaccine. C-MED 100 had been earlier found in preclinical studies to produce immune stimulating and anti-inflammatory effects. C-MED was concluded to enhance the immune response through observed lymphocyte/neutrophil ratios of peripheral blood, and the reduction of decline of antibody titer responses to the pneumococcal vaccination at 5 months. No negative side effects were found either through medical examination, clinical chemistry or blood cell analysis (Lamm et al., 2001).

Anti-cancer

In a preliminary study, a decoction of U.tomentosa bark was given to a smoker for 15 days and found to decrease the mutagenicity induced by Salmonella typhimuriium TA98 and TA100 through urine analysis. Fractions of the plant extract were tested in vitro and found to have no mutagenic effect in strains of S. typhimurium, bur rather to be able to protect against photomutagenic effects of 8-mehoxy-psoralen and UVA. These studies confirmed earlier reports of antimutagenic activity of cat’s claw, but not of its proported mutagenic effects (Rizzi et al., 1993).

Safety / Dosage

Generally dosage ranges from 20-60 mg daily for a week, and then 20 mg daily as a maintenance dose. The standardized product containing pentacyclic oxindole alkaloids (POAs) that is manufactured by Immodal Pharmaka (Saventaro) is standardized to contain a minimum of 260 µg POAs in every 20 mg dose. The C-MED-100 product (manufactured by CampaMed) is manufactured to eliminate the indole alkaloids (<0.05%) and other high molecular weight compounds such as tannins, and to contain 8% or more carboxyl alkyl esters. The recommended dose of this product is 350 mg daily (McKenna et al., 2002).

Cat’s claw is generally regarded as safe, but it is not recommended for pregnancy or lactation because it has not been fully evaluated. Initial and temporary gastrointestinal side effects are sometimes experienced, such as gas, bloating, nausea and diarrhea.

References

1.Akesson Ch, Pero RW, Ivars F. C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo. Phytomedicine. 2003 Jan;10(1):23-33.

2.Lamm S, Sheng Y, Pero RW. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Phytomedicine. 2001 Jul;8(4):267-74.

3.McKenna D, Jones K, Hughes K, Humphrey S. Botanical Medicines: The Desk Reference for Major Herbal Supplements, 2nd Ed. 2002 Haworth Press; Binghamton, NY

4.Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002 Apr;29(4):678-81.

5.Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001 Sep;50(9):442-8.

6.Rizzi R, Re F, Bianchi A, De Feo V, de Simone F, Bianchi L, Stivala LA. Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J Ethnopharmacol. 1993 Jan;38(1):63-77.

7.Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002 May;9(4):325-37.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Zinc

Overview

Zinc is an essential trace mineral that functions as part of about 300 different enzymes. As such, zinc plays a role in numerous biochemical pathways and physiological processes. More than 90% of the body’s zinc is stored in the bones (30%) and muscles (60%), but zinc is also found widely distributed in small amounts in virtually all body tissues. The richest dietary sources of zinc are seafood (especially oysters), meat, fish, eggs, and poultry. Because of the varied roles of zinc in the body, claims for zinc-containing dietary supplements are numerous, including those for improved wound healing, general immune system support (including reduced severity and length of colds and upper respiratory tract infections), and support of various “male” aspects of health (supporting a healthy prostate gland, preventing benign prostatic hyperplasia, and increasing fertility via enhanced sperm production.

Comments

Zinc lozenges have become one of the most popular natural approaches to treating the common cold and the scientific evidence generally supports this use for short periods of time (1-2 weeks). Zinc lozenges appear to reduce cold symptoms such as sore throats, hoarseness and coughing – and may even be able to shorten the duration of colds by a full day or so. Like vitamin C, zinc is an essential nutrient for optimal functioning of the immune system – and they both possess significant antiviral activity when consumed at elevated levels for a short period of time. It also appears, however, that some forms of zinc lozenges may be more effective than other forms (due to the total amount of ionized zinc that the lozenge actually releases into the mouth and throat). At least one study has shown that lozenges containing zinc gluconate plus citric acid, sorbitol or mannitol may not deliver high enough levels of ionized zinc – whereas those lozenges which contained glycine (an amino acid) appeared to deliver a higher quantity of ionized zinc.

Scientific Support

Because zinc is an essential part of nearly 300 different biochemical pathways, “structure/function” claims can be made for the nutrient’s role in a wide variety of processes including digestion, wound healing, energy production, growth, cellular repair, collagen synthesis, bone strength, cognitive function, carbohydrate metabolism (glucose utilization and insulin production), and reproductive function. Even mild zinc deficiency has been associated with depressed immunity, decreased sperm count and impaired memory. Perhaps the most popular claim for zinc is for its role in immunity, where zinc delivered in lozenge form may interfere with the replication of the cold virus (rhinovirus).

Zinc deficiency is common in developing countries and in some elderly and athletic populations (Bogden et al. 1990, Bunker et al. 1994, Johnson and Porter 1997, Mahalanabis et al. 2002, Penny et al. 1999, Sazawal et al. 1998, Singh et al. 1994) and in these populations, zinc supplementation at dosages of 10-25mg/day – improves most markers of immune function and duration of illness (diarrhea and upper respiratory tract infections).

Evidence exists to support the use of zinc lozenges in reducing the duration and severity of colds. Although concentrated zinc lozenges can help kill cold viruses in the mouth and throat, it is important to begin using them as soon as possible following the onset of cold symptoms (ideally within the first 24-48 hours). Test tube studies have shown that zinc can block the cold virus from replicating – an effect that could help the body’s natural immune defenses “get a jump” on killing the viruses. Most studies of the effect of zinc lozenges (typically zinc gluconate or zinc acetate) on the common cold have shown that subjects in the supplement group tend to have fewer “symptomatic” days (on average 2-3 fewer sick days) compared to subjects receiving a placebo (measured in terms of coughing, sore throat, nasal congestion and headache).

Occasionally, high dose zinc supplements are recommended to diabetic patients. Such patients commonly suffer from increased loss of zinc and reduced body stores of zinc. High doses of zinc have been shown to mimic the effects of insulin in reducing blood sugar and promoting wound healing. These effects, however, should be considered preliminary and high dose zinc supplements are not recommended for diabetics except on the advice of their personal physician.

Exercise performance has also been associated with adequate zinc status – especially in athletes who avoid red meat, concentrate their diets too much on carbohydrates or follow an overly restricted dietary regime. Low zinc intake (below 3mg/day) has been linked to reduced activity of a zinc-containing enzyme in red blood cells called carbonic anhydrase (which helps red blood cells transport carbon dioxide from tissues to the lungs to be exhaled). Mild to moderate zinc deficiency can lead to significant reductions in the body’s ability to take up and use oxygen, remove carbon dioxide and generate energy during high intensity exercise.

Safety / Dosage

The short-term use of zinc at therapeutic doses for cold relief (see below) is assumed to be safe and chronic supplementation with zinc at levels 2-3 times the current RDA should not be expected to pose any significant adverse side effects. However, high doses of zinc are not recommended for periods of more than two weeks due to concerns of immune system suppression, interference with copper absorption and other long-term health effects such as increased risk for heart disease. High doses of zinc (gram levels) can cause nausea, diarrhea, and vomiting.

The Daily Value for zinc is 15mg per day – a level that should be adequate for support of bone metabolism and optimal physical performance. As therapy for colds, however, higher levels are required – with levels in the range of 13-23mg (in lozenge form) taken every 2-4 hours for no more than 2 weeks. These levels appear to be quite effective for reducing duration and severity of cold symptoms compared to not taking zinc lozenges. It is also important to note that other supplements, particularly high levels of calcium and iron can decrease zinc absorption, while complexation (chelation) with various amino acids (such as glycine, histidine and aspartate) or other organic compounds (such as gluconate or picolinate) may increase zinc bioavailability. Zinc supplementation can also reduce absorption of copper (Bonham et al. 2003) and iron (Donangelo et al. 2002), but may also potentiate the effect of supplemental vitamin A on night vision and immune parameters (Christian et al. 2001).

References

1.Abbasi AA, Prasad AS, Rabbani P, DuMouchelle E. Experimental zinc deficiency in man. Effect on testicular function. J Lab Clin Med. 1980 Sep;96(3):544-50.

2.Bogden JD, Oleske JM, Lavenhar MA, Munves EM, Kemp FW, Bruening KS, Holding KJ, Denny TN, Guarino MA, Holland BK. Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly. J Am Coll Nutr. 1990 Jun;9(3):214-25.

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15.Penny ME, Peerson JM, Marin RM, Duran A, Lanata CF, Lonnerdal B, Black RE, Brown KH. Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru. J Pediatr. 1999 Aug;135(2 Pt 1):208-17.

16.Peretz A, Neve J, Jeghers O, Pelen F. Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases. Am J Clin Nutr. 1993 May;57(5):690-4.

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18.Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998 Jul;102(1 Pt 1):1-5.

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EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.