Ribose Supplements

Ribose is a five-carbon simple sugar (a pentose) that forms the carbohydrate portion, or backbone, of RNA and DNA molecules. When combined with adenine, ribose produces adenosine, one of the components of the energy currency of the cell, ATP. Ribose is used in the body in several specific ways. It can be converted into pyruvate and enter into the pathways of energy metabolism, or it can be used to manufacture nucleotides, the primary building blocks for important structures in the body such as RNA, DNA, and ATP. As a result, ribose supplements are typically marketed for increasing energy levels, exercise endurance, and muscular power output.



Clearly, anybody concerned with managing diminished blood flow to the heart or muscle tissues would be interested in ribose supplementation. In particular, people who experience chest pain, shortness of breath, or leg pain during exercise may want to consider ribose as a daily dietary supplement. The casual or occasional exerciser is unlikely to benefit from ribose supplements except in the case of several back-to-back days of intense exercise. For the "weekend warrior," who probably has enough time between exercise sessions to fully recover ATP levels, supplemental ribose is not recommended. Competitive athletes, who may be training once or more per day, could notice very modest benefits such as increased power output and increased time to exhaustion with regular ribose supplementation (because of enhanced ATP resynthesis following exercise-induced depletion); required doses, however, are large (more than 10 g/day) and expensive.



Because ribose can serve as a precursor to adenosine (the A in ATP} and seems to stimulate the production of ATP (in laboratory studies), the theory behind ribose supplementation is that it maximizes ATP stores and therefore increases cellular energy stores for improved exercise performance and fatigue prevention.



In the cell, ATP loses its phosphate groups to generate energy. Losing one phosphate turns ATP (triphosphate) into ADP (diphosphate) and finally into AMP (monophosphate). Adenine or adenosine (no phosphates) can either be converted back to AMP or lost from the cell. The conversion back to AMP/ADP/ATP or the "salvage" of adenosine requires a ribose-containing molecule known as 5-phosphororibosyI-l-pyro-phosphate (PRPP). If this salvage does not take place, the adenosine is lost and must be converted "from scratch" a process known as de novo synthesis, which again requires the ribose-containing PRPP.



Ribose has been understudy as a therapy for cardiac ischemia (reduced blood flow to die heart) for a number of years (Pasque and Wechsler, 1984). The data from those studies clearly indicate that ribose can help improve heart function during and following periods of reduced blood flow and oxygen delivery (Erickson, 1990), Under conditions of constricted blood and oxygen flow to heart and muscle tissue, ATP levels have been shown to decrease by as much as 50%. This finding is not unexpected, but the fact that creatine phosphate levels recover relatively quickly while ATP levels may remain depressed for several days suggests that adenosine levels may not be adequately maintained. In animal studies, supplemental ribose permits recovery of approximately 85% of normal ATP levels within 24 hours following restricted circulation.



In patients with coronary artery disease, supplemental ribose allows subjects to exercise forsignificandy longer periods than they could before they consumed ribose and longer than subjects who consumed a placebo supplement (Pliml et al., 1992). During intense exercise, ATP levels are reduced 10-20%, which may be attributed to the loss of adenosine and inadequate resynthesis of ATP (Wagner et al., 1991). In some muscle fibers, complete resyndiesis of ATP may require 24-96 hours (1-4 days) to fully recover from exhaustive exercise. Supplemental ribose has the potential to increase the rate of adenosine production and ATP synthesis following exhaustive exercise by approximately 3-4 times, meaning that recovery of ATP stores can be reduced from 1-4 days to 6-24 hours (Wagner et al., 1991).



Because ribose is found in all cells of the body, it is generally recognized as a nontoxic substance. Supplemental doses of as much as 60 g/day have been given with no significant side effects (Erickson, 1990). At such high levels, die possible occurrence of gastrointestinal distress, diarrhea, and hypoglycemia are more likely. For purposes of maintaining elevated levels of ribose in the blood, smaller doses of 3-10 g/day of ribose are common in commercial dietary supplements, but as noted earlier, the clinical evidence for energy or endurance benefits of such doses in healthy subjects has been disappointing.

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Tribulus - Tribulus Terrestris

Tribulus is a traditional Chinese medicinal herb that has gained attention lately for its uses in enhancing sexual and athletic performance and treating painful urination and as a general tonic (Anand et ah, 1994).



The main active components in tribulus appear to be steroidal saponins and protodioscin. Tribulus has been proven to improve sexual desire and erectile function by converting protodioscin to DHEA. Both phyto-chernicals have been shown in preclinical tests to stimulate sexual desire and function .



Few well-designed studies have been conducted on Tribulus terrestris for its primary indications of sexual performance and athletic performance. Of the few human clinical studies involving treatment with only tribulus, the results were favorable. A few other studies exist in the areas of sexual performance and athletic performance, but they used tribulus in a mixture with other supplements, and it is not known how much the tribulus contributed to the clinical results. Of note, a heart drug made from Tribulus terrestris saponins is being recommended for clinical therapy and prevention of atherosclerosis in Russia (Kern ertelidze et al., 1982). Overall, even though tribulus is one of the most popular ingredients in supplements for bodybuilding, clinical support to back up its claims is still lacking.



Sexual Performance

Nikolova and Stanislavov (2000) performed a clinical study involving 51 patients using an extract of Tribulus terrestris (Tribestan) and found statistically significant improvement in parameters to measure infertility.



The use of tribulus treatment over 3 months produced reductions in the leukocyte count and the locally secreted immunoglobulins, elevation of tt-amylase levels, and normalization of seminal parameters. The authors noted that the treatment with Tribulns terrestris extract had a side benefit of improving overall male health, indicated by decreased cholesterol and triglyceride levels and elevated levels of lipoproteins by the end of the study.



Stanislavov and Nikolova (2000) reported thai in 15% of the infertile couples in Russia, 9% of males and 15% of women showed signs of infertility that might have been the result of imrnunological health. In a study of a cohort of this group, Tribulus terrestris extract (Tribestan) was chosen because of the presence of furostanol compounds in the plant and the absence of reported toxicity in humans. As a result of treatment, conception was reportedly good in these couples, especially when the males had high liters of sperm antibodies. The authors noted that due to the good results, they recommended treatment in similar cases in practice.



In a double-blind study with Tribulus terrestris, 45 men with fertility problems {moderate idiopathic oligozoosperms) were given a dry-powder extract or a placebo. After 3 months of treatment, 7 of the 36 men treated successfully conceived with their wives. In the treatment groups, significant increases in normal acrosome morphology and aero-some reaction test were found.



Athletic Performance

Ten highly trained cyclists were given a supplement of Tribulus terrestris and ipriflavone or a placebo for 38 days. Cyclists in the active group improved hormonal markers of overtraining and performance during the period of intense training and competition (McGregor et al., 2000). Street et al. (2000) gave capsules containing 250 mg of Tribulus terrestris, 100 mg of 7-ispropoxyisofavone, 100 mg ofAvena saliva, and 50 mg of saw palmetto to two bodybuilders to determine the effect of the supplement on plasma testosterone and luteinizing hormone. As part of the normal weight-lifting regime, the supplements were administered for 2 weeks, 8 capsules 2 times daily. The luteinizing hormone and plasma



Sports Supplements

Testosterone tevels were found not to change within the period of supplementation, nor were biochemical measures of liver function changed.



Hor a standardized extract (60% saponins), the dosage is 100-500 mg 3 times daily; an unspecified preparation of tribulus was used in a couple of clinical studies at the dosage of 750-1,350 mg/day along with other supplements (Brown et al., 2000, 2001a, 2001b, 2001 c).



The only reported side effect of tribulus is frequent urination, and because of its diuretic properties, tribulus is not recommended in cases of dehydration (Singh and Sisodia, 1971). There are no known drug interactions with tribulus.



Possible association with hepatotoxicity, photosensitization, and a disease called geeldikkop have been made with the ingestion of large amounts of tribulus by sheep but have never been confirmed (Bourke, 1984; Clastonbury, 1984).

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Dietary Supplements Containing Inosine

Inosine is part of a chemical family called purine nucleotides and acts as a precursor to adenosine, an important molecule for cellular energy. Inosine can be found in brewer's yeast and organ meats, such as liver and kidney, and is available as a supplement in its purified form.



Dietary supplements containing inosine are often marketed with claims for increased energy levels and endurance performance, enhanced adenosine triphosphate (ATP) production, improved heart function, and reduced lactic acid accumulation during intense exercise.



Many of the effects attributed to inosine stem from its potential role in increasing levels of a compound known as 2,3 diphosphoglycerate (DPG) in red blood cells. An enhanced 2,3 DPG level would ease the release of oxygen from the blood cells to the tissues and, in theory, enhance energy generation, promote lactic acid removal, and improve exercise performance overall.



Because there are no convincing studies demonstrating the beneficial effects of inosine as a dietary supplement, it is not recommended as a stand-alone dietary aid. Inosine is commonly contained as part of an overall mixture of ingredients in dietary supplements that may contSeveral studies have investigated the effects of inosine supplementation on aerobic performance in athletes, yet none have shown convincing benefits associated with the supplement. In at least two studies, a potential for inosine to interfere with energy metabolism was suggested, particularly in high-intensity sprint-type events.



Inosine has many possible metabolic roles in the body. Preliminary information suggests that inosine might stimulate axon growth from healthy nerve cells to injured nerve cells in the brain and spinal cord of the central nervous system (Bianchi et al., 1999). It penetrates the cell walls of both cardiac and skeletal muscles, where it promotes the generation of ATP, the energy substance that allows muscles to contract (Febbraio and Dancey, 1999; Norman, 1995). It also serves as a precursor ribute to energy metabolism.



Hypoxanthine, which may be phosphorylated into the nucleotide inosine monophosphate (IMP). IMP is claimed to be an important regulator between adenine and guanine nucleotide synthesis and may lead to the formation of ATP. Increased production of ATP leads to improved respiration and oxygen transport and serves to enhance all athletic performance, whether aerobic or anaerobic in nature. IMP also helps to maintain glycogen breakdown by activating phosphorylase b and increasing the formation of uric acid.



Inosine also contributes to erythrocyte metabolism by promoting the production of 2,3 DPG, which is necessary for die transport of oxygen molecules from the red blood cells to the cell for energy. Both inosine and hypoxanthine are believed to be vasodilating agents, which may enhance blood flow to the heart and skeletal muscles and lead to improvement of various heart conditions (Iwasa et al., 1997; Kipshidze et al, 1978).



A double-blind, placebo-controlled, crossover trial was conducted on 9 highly trained endurance runners to investigate the ergogenic effect of oral inosine supplementation on a 3-mile run time and oxygen uptake (VO2) peak. Each patient underwent four trials, which followed the same protocol and measured three separate tests within each trial: a 13-rninute subrnaximal treadmill warm-up, a 3-mile treadmill run test, and a maximal treadmill run to test VO2 peak. Patients were instructed to prepare for each trial as if preparing for a race. The patients were given 6,000 mg (3 doses of 2,000 mg) of inosine per day for 2 days or matching placebo prior to testing. The last dose was taken within 2 hours of testing. The results showed no significant effect of inosine in the 3-mile treadmill run test or in the maximal VO2 peak test (Williams et al., 1989).



Another randomized, double-blind, placebo-controlled, crossover trial was conducted in 7 healthy male volunteers to evaluate the use of inosine over a period of 5-10 days at a dosage of 10,000 mg/day on measures associated with aerobic and anaerobic performance. All patients completed three trial sessions, which included a series of three stationary cycling performance tests; a 5-6-second sprint, a 30-second sprint, and a 20-minute time trial. These trial sessions were completed prior to the study (at baseline), on days 6 and 11. Patients completed the performance tests after supplementation with inosine (two equal doses taken early morning and late afternoon, dissolved in orange juice) or a placebo. Each trial was separated by a 6-week washout period. The results showed no significant differences for any of the variables measured. It was concluded that inosine has no ergogenic effects, does not improve performance, and may cause possible health problems if taken over long periods (McNaughton et al., 1999).



A similar double-blind, placebo-controlled, crossover trial was performed on. 10 competitive male cyclists. These patients completed a bike test, a 30-minute self-paced cycling performance, and a supramaximal cycling sprint following 5 days of oral supplementation with 5,000 mg/ day of inosine and a matching placebo. The results showed no differences between the inosine and placebo groups within each test performed(Starling et al., 1996). These findings demonstrate that prolonged inosine supplementation does not appear to improve aerobic performance and short-term power production during cycling.



Another 8-week, double-blind, placebo-controlled, crossover trial was conducted to examine the effects of the Coenzyme Athletic Performance System (CAPS) on endurance performance to exhaustion. Eleven highly trained male triathletes were given 3 daily doses of CAPS or a matching placebo for two 4-week periods. CAPS consisted of 100 mg of coenzyme QlO, 500 mg of cytochrome C, 100 mg of inosine, and 200 III of vitamin E. A 4-week washout period separated the two treatment groups. After each treatment period, an exhaustive performance test consisting of a 90-minute treadmill run followed by cycling until exhaustion was performed. The results showed that the mean time to exhaustion and blood parameters for the patients using CAPS were not significantly different from the placebo group. In conclusion, CAPS had no apparent benefit on exercise to exhaustion (Snider et al., 1992).



The overall results obtained from these trials suggest that the anecdotal effects of inosine as stated by athletes and manufacturers hold little weight when tested in the laboratory'-. Therefore, inosine supplementation has no athletic performance benefit and may be detrimental to general health.



According to Japanese researchers, inosine may be used as a treatment for various heart conditions. A study was performed to evaluate the effect of the nucleoside inosine on the intracardiac hemodynamics and the contraction and relaxation of a diseased myocardium. The study included 102 patients with a macrofocal myocardial infarction. Twenty-two patients received inosine by intravenous drip in a single dose of 200 mg in the acute stage of infarction, SO patients were given inosine pills in a daily dose of 800 mg in the restoration period for 1 month, and 20 patients were given a placebo. Comparative appraisal of treatments showed prevailing improvement in die condition of patients treated with inosine. These patients had positive EGG dynamics, increased cardiac output, and decreased peripheral resistance. Inosine achieved maximum effect by 60-90 minutes after the beginning of the infusion (Yabe and Yoshimura, 1981).



Another study administered 200 mg of inosine through a central vein to 16 patients with various cardiac diseases, including effort angina pectoris, myocardial infarction, valvular disease, idiopathic cardiomyopathy, and congenital heart disease. Left ventricular performance was assessed by the time course of various hemodynamic parameters, including ejection fraction. The results demonstrated that inosine caused a significant decrease in pulmonary wedge pressure, left ventricular end-diastolic pressure, and systolic left ventricular pressure. Inosine caused increases in all of the other hemodynamic parameters, such as cardiac output and ejection fraction. Quantitative evaluation disclosed the beneficial effects of inosine on the left ventricular function through the remarkable load-reducing effect and the unequivocal positive inotropic effects (Iwasa et al., 1997). In general, supplemental inosine appears to be safe at doses of as much as 5-6 g for several weeks. In susceptible people, however, inosine supplementation may lead to buildup of uric acid levels. Uric acid is a byproduct of inosine metabolism and may lead to painful symptoms of gout, such as arthritic joints and toes caused by deposits of uric acid crystals.

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Dietary Supplements: Nicotinamide Adenine Dinucleotide (NADH)

NADH is the abbreviation for nicotinamide adenine dinucleotide, with the H indicating the reduced form that has an extra hydrogen atom. NADM functions as a coenzyme, meaning that it is a required cpfactor for a metabolic process. In the case of NADH, coenzyme functions include roles in energy generation and the production of neurotransmit-ters such as dopamine and norepinephrine. Thus, NADH supplements are generally promoted for increasing energy levels, reducing CFS, treating jet lag, and enhancing memory and cognitive function.



NADH supplements typically cost about $1 per 5-mg dose; therefore, an effective dose of the supplement may cost between $2 and $4 per day. Because of the nonexistence of any reliable treatment for chronic fatigue syndrome, the preliminary antifatigue benefits of NADH are promising. Nevertheless, the preliminary nature of these results also means that NADH may be most useful as an adjunct to more established antifatigue supplements such as cordyceps, rhodiola, and ginseng.



The precise cause of CFS is unknown (Calabrese et al., 1992). Symptoms include prolonged and debilitating fatigue, inability to concentrate, flu-like symptoms, muscle weakness, joint pain, headaches, and sleep disturbances (Chester, 1997; Komaroff and Buchwald, 1991). CFS affects about 500,000 Americans, but no effective treatment is known (Gantz and Holmes, 1989; Houde and Kampfe-Leacher, 1997). Researchers theorize that CFS stems from a lack of the chemical responsible for cellular energy, ATP (Klonoff, 1992). One theory is that both infections and stress deplete cellular ATP levels and lead to chronic fatigue, and that supplemental levels of NADH can stimulate ATP production and provide benefits to people suffering from fatigue and cognitive dysfunction (Colquhoun and Senn, 2000). Further benefits from NADH may stem from its role in stimulating the production of the neurotransmitters dopamine and norepinephrine (involved in brain function and memory) as well as from the stimulation of tyrosine hydroxylase, an enzyme involved in synthesizing neurotransmitters (Birkmayer el al., 2002).



Among the dozen or so clinical reports of NADU supplementation, however, only two arc randomized, double-blind, placebo-controlled trials (Birkmayer el al., 2002; Forsyth et a!., 1999). Of the many open-label studies of NADU administration to patients with Alzheimer disease, dementia, or Parkinson disease, most of the studies showing a positive effect come from the same clinic in Austria {Birkmayer et al., 2002), and the dosing regimens include oral as well as intravenous, parenteral, and intramuscular routes of administration. The positive benefits of NADU supplementation in these open-label studies have not been duplicated by other clinics or laboratories, and some open-label studies have shown no benefit of NADH supplements (10 rng/dayfor3 months) in cases of mild-to-moderate Alzheimer disease (Rainer et al., 2000).



In the two existing well-controlled studies of NADH supplementation, 10-20 mg of NADH showed some promising antifatigue effects. In one study {Forsyth et al., 1999), 10 mg/day of NADH for 4 weeks was effective in alleviating generalized symptoms of CFS in about one third of patients. In another study (Birkmayer el al., 2002), a 20-mg acute dose of a sublingual form of NADH improved cognitive function, mood, and sleepiness in subjects suffering from jet lag.



Some people report mild side effects such as nervousness and loss of appetite in the first few days of taking NADH. No serious side effects are documented, and animal studies have shown no problems associated with NADH supplementation (Birkmayer and Nadlinger, 2002). Commercial NADH supplements are generally available in 2.5-mg and 5-mg tablets, with suggested dosages ranging from 2.5-15 mg/day, depending on individual requirements (e.g., therapy or maintenance).

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Dietary Supplements: Rhodiola

Rhodiola comprises more than 200 related species of plants in the Crassulacea family and is generally found in the arctic mountain regions of Siberia (Kelly, 2001). Of the many species of rhodiola, only two have been studied at any appreciable level in humans: Rhodiola rosea and Rhodiola crenulalci ("Rhodiola rosea," 2002) The root of the plant is used medicinally and is also known as arctic root, golden root (for rosea), and more recently, crenulin (for crenulata). Rhodiola has been used for centuries to increase the body's resistance to physical and mental stresses (Zhang et al., 1989), As a modern-day dietary supplement, rhodiola is typically promoted for boosting energy levels, relieving stress and anxiety, and enhancing athletic performance.



Rhodioln roscn extract appears to be valuable as an adaptogen, increasing the body's ability to deal with a number of psychological and physiological stresses. Of particular value is the theoretical role of rhodiola in increasing the body's ability to take up and use oxygen, an effect similar to that of cordyceps, which may explain some of the nonstimulant "energizing" effects attributed to the plant. Rhodiola is often called the "poor man's" cordyceps based on ancient stories in which "commoners" used rhodioia for energy because the plants grew wild throughout the Rhodiola is typically considered an adaptogen (like ginseng) and is believed to invigorate the body and mind to increase resistance to a multitude of stresses. The key active constituents in rhodiola are believed to be rosavin, rosarin, rosin, and salidroside (Kelly, 2001), which are reported in animal studies to influence levels of neurotransmitters (serotonin, dopamine, and norepinephrine), catecholamines, and free radicals (Maslova et al., 1994; Ohsugi et al., 1999; Rege et al., 1999)



Unfortunately, most of what we know about the clinical effects of rhodiola supplementation comes from a handful of small studies in which standardized extracts of both Rhodiola rosea and Rhodiola crenulata have been shown to increase cognitive function and mental concentration while reducing feelings of general fatigue (Darbinyan et al., 2000, Spasov et al., 2000a, 2000b). One of the theoretical mechanisms of action for rhodiola's antifatigue effects is an enhancement of oxygen efficiency; although some studies have observed this effect (Ha et al., 2002), other studies have not (Wing et al., 2003). A possible reason for the discrepancy in these results is study design, with positive-effect studies tending to have larger numbers of subjects, longer durations of supplementation, and more complete characterizations of study materials (standardized Rhodiola extracts).



For example, one study of rhodiola followed 15 subjects supplemented with rhodiola for 7 days under simulated high-altitude conditions (4,600 meters) and found a reduction in hypoxia-induced oxidative stress but no change in hemoglobin saturation or blood oxygen levels (Wing et al., 2003). In contrast, a similar study (Ha et al., 2002) of 24 subjects living at a higher altitude (5,380 meters) for a longer duration (1 year) showed a beneficial effect of rhodiola supplementation on blood oxygen levels when rhodiola was given over a longer period (24 days).



Another significant factor among the handful of clinical studies on rhodiola is the material being studied, with well-characterized extracts (standardized to salidroside, rosavin, and other active/marker compounds) showing significant beneficial effects, while less well-characterized material (nonstandardized extracts and raw rhodiola root) tending to show modest or no beneficial effects. For example, three well-controlled studies of a standardized extract of Rhodiola rosea have shown benefits in reducing mental and physical fatigue in physicians working night duty (Darbinyan et al., 2000) and students under stress (Spasov et al., 2000a, 2000b).



Rhodiola rosea extract is thought to be quite safe. There are no known contraindications or interactions with other drugs or herbs, but there are anecdotal reports of mild allergic reactions (rashes) in some persons.


General dosage recommendations for extracts of both Rhodiola rosea and Rhodiola crenulata are typically in the range of 100-600 mg/day. Ideally, a standardized Rhodiola extract is preferred, with the best efficacy demonstrated for extracts with active/marker compounds in the ranges of 3-6% rosavin and 1-2% salidroside (Kelly, 2001).

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Dietary Supplements: Buckthorn

Sea buckthorn is a small shrub that produces berries used in Traditional Chinese Medicine and known since ancient Greek times for its ability to enhance energy, promote weight gain, and heal the skin and make it look younger. In more modern times, studies have found that it may be a good antioxidanl and that it contains palmitoleic acid, a rare fatty acid that is a component of our skin and promotes skin health. Other uses for sea buckthorn include promoting cardiovascular health, healing ulcers, and protecting the skin against damage from the sun's ultraviolet rays. Sea buckthorn oil is high in vitamin E, carotenoids, sterols, and the fatty acids: palmitic (16:0), oleic (18:ln-9), palmitoleic (16:ln-7), linoleic (18:2n-6), and a-linolenk (18:3n-3; Johansson et al., 2000).



Clinical research has not substantiated the claims for sea buckthorn as an energizer; however, experimental and clinical studies have found that it shows promise for promoting cardiovascular health, antioxidant functions (antiaging, cardiovascular), and as a wound and tissue healer.



Wound Healing and Dermatitis Treatment

A synthetic preparation of sea buckthorn oil (Aekol) was compared in a clinical setting on the treatment of 41 patients with natural sea buckthorn and standard wound-healing remedies. The patients studied exhibited various wound-healing complications, including open injuries on their limbs, pyoderma or necrosis from skeletal trauma, and tissue necrosis after operations. From the study ofvarious clinical and biochemical parameters for wound healing, it was concluded that Aekol exhibited a similar efficacy as natural sea buckthorn extract and far exceeded the traditional remedies (Kostrikova et al., 1990).



Yang et al. (2000) conducted a placebo-control led parallel study to examine the effect of the daily ingestion of 5 g of sea buckthorn seed oil compared with pulp oil or paraffin oil for 4 months. The outcome measure was the fatty acid composition of skin glycerophospholipids in patients with atopic dermatitis before and after treatment. The seed oil ingestion caused only a slight increase in docosapeniaenoic acid (22:5n-3) and a decrease in palmitic acid (16:0). The authors concluded that the composition of glycerophospholipids in the skin is well buffered and not significantly affected by short-term dietaiy changes.



Yang et al. (1999) studied the effect of daily supplementation for 4 months of 5 g of either sea buckthorn seed oil, pulp oil, or paraffin oil on atopic dermatitis. In a placebo-controlled, double-blind study, the clinical evaluation of each treatment on atopic dermatitis was evaluated, as well as changes in plasma and skin lipid content. The sea buckthorn seed oil was characterized as high in linolek (34%), a-linolenic (25%), and oleic (19%) fatly acids, whereas the pulp oil was high in palmitic (33%), oleic (26%), and palmitoleic (25%) fatty acids. Significant improvements were observed for dermatitis symptoms in the groups treated with pulp oil and paraffin oil, but no changes in the seed oil group were noted. No changes were detected in levels of triacylglycerols, serum total, or specific immunoglobulin E in either of the groups.



Cardiovascular Health

Johansson et al. (2000) studied the effect of sea buckthorn berry oil (supercriiical carbon dioxide extracted) on risk factors of cardiovascular disease in a pilot clinical study. After a treatment period of 4 weeks, the ingestion of 5 g of sea buckthorn oil was found to have no effect on phospholipid fatty acids, plasma lipids, or glucose. The treatment group, however, did show a marked decrease in the rate of adenosine-5'-diphos-phate-induced platelet aggregation and maximum aggregation.



The effect of supplementation of the total flavone fraction of sea buckthorn was studied on the sympathetic nerve activity in hypertensive patients. Specifically, the authors were investigating whether this fraction was able to exert an inhibitory effect on sympathetic activity after supine isometric exercise. The 88 participants were given the sea buckthorn flavone extract, nifedipine, orverapamil. After 8 weeks of treatment, the sea buckthorn flavone extract was found not to alter the sympathetic activity in the treatment of hypertension, but it did exhibit an inhibitory effect on the sympathetic activity after supine isometric exercise. The authors noted that for this reason, sea buckthorn flavones might provide a clinical benefit (Zhang et al., 2001).



Hccleston et al. (2002) studied the antioxidant profile of sea buckthorn juice and its effect on various biochemical markers in cardiovascular health: plasma lipids, low-density lipoprotein (LDL) oxidation, platelet aggregation, and plasma soluble cell adhesion protein concentration. This study was in response to the growing evidence that antioxidanl nutrients were able to affect cell response and gene expression relating to the oxidative processes that contribute to atherogenesis. After 8 weeks of treatment with sea buckthorn juice, there were no significant changes in plasma total cholesterol, LDL-C, platelet aggregation, or plasma.



Because few clinical studies have been performed on sea buckthorn, and because it has a diversity of potential uses, the optimal dosage recommendations are difficult to ascertain. Generally, it is taken orally, about 250-500 mg/day as an energy promoter, and up to 1 g or more as a topical skin protector or wound healer.

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Ginseng Supplements

Ginseng refers lo a group of adaptogenic herbs from the plant family Araliacae. Commonly, the term ginseng refers to "true" ginseng (Panax ginseng C.A. Meyer), as well as to a related plant called Siberian ginseng (Eleutherococcus seniicosus, or eleuthero for short). Medicinal preparations are made from the roots of the plants. Panax ginseng has been used in Traditional Chinese Medicine (TCM) for thousands of years as a tonic indicated for its beneficial effects on the central nervous system, protection from stress, antifatigue action, enhancement of sexual function, and acceleration of metabolism.



Siberian ginseng did not come into the picture as a botanical remedy until the twentieth century. Found in the northern regions of the former Soviet Union, the roots of Eleutherococcus seniicosus were sought out as a cheaper substitute for the expensive Oriental ginsengs. Soviet researchers found Siberian ginseng to be an excellent tonic to enhance athletic performance as well as to strengthen the body during times of stress.



Several other "ginsengs" are used as adaptogenic tonics throughout the world; among them are Panax quinquefolium (or Panax fjuijiquefoiius, also known as American ginseng, with a rich history of use by Native Americans) and ashwagandha, sometimes called Indian ginseng (not a true ginseng but with a long history of medicinal use by ayurvedic healers in India).



American ginseng is the most similar to the true Panax ginseng and is highly prized in the Orient, where it is thought to provide a "cooler" invigoration than the native Panax ginseng (considered "warming" by traditional Chinese healers).



In general, the various ginseng supplements available in the U.S. market are claimed to increase energy levels, relieve stress, enhance athletic performance, enhance immune system function, control blood sugar, improve mental function, and promote general well-being. In most of these functions, ginseng, whether Siberian, Panax ginseng, or one of the other varieties, is often termed an adaptogen a therapeutic and restorative tonic generally thought to produce a "balancing" effect on the body. The properties typically attributed to adaptogens are a nonspecific increase in resistance to a wide range of stressors (including physical, chemical, and biological factors) as well as a "normalizing" action irrespective of the direction of the pathological changes. In general, an adaptogen can be thought of as a substance that helps the body adapt to stress.



Among the many herbs promoted as energy boosters, Asian ginseng is by far the most popular. Although the term ginseng actually encompasses a family of roots, Panax ginseng, the type grown in China, Korea, and Japan, is die type generally known for its energetic and antistress properties. In TCM, Panax-ginseng is used as a tonic properties. In general terms, an adaptogen is a substance that boosts energy and aids in combatting stress and remaining calm. The research on ginseng's benefits as a tonic and energy booster is equivocal. Some studies have shown benefits in increasing energy levels in fatigued sub jects (Vogler et al., 1999; Wang et al., 1983), but most studies on ginseng as an aid to athletic performance have shown no effect (Bahrke and Morgan, 2000). The differences among study findings may have been the result of many commercially available ginseng supplements actually containing little or no ginseng at all; many researchers often take it for granted that a given product selected off the shelf for study will actually contain what it claims (not always a good assumption). The clearest indication that a supplement contains something other than real ginseng is the price; ginseng root is a very expensive ingredient, and "bargain" ginseng products may not contain real ginseng, enough ginseng, or the active saponin compounds that are thought to deliver ginseng's antifatigue and adaptogenic effects.



Siberian ginseng (eleuthero), is not truly ginseng (it is a shrub, rather than a root) but it is a close enough cousin (same botanical family but different genus) to deliver some of die same energetic benefits. Eleuthero is used in popular sports supplements. The Siberian form of ginseng is generally a less expensive alternative to true Asian or Panax ginseng, though it may have more of a stimulator;' effect rather than an adaptogenic effect (not necessarily a bad thing if you just need a boost). Often promoted as an auhletic performance enhancer, eleuthero may also possess mild-to-moderate benefits in promoting recover}' following intense exercise, perhaps the result of an enhanced deliver}' of oxygen to recovering muscles.



Ashwagandha is an herb from India that is sometimes called Indian ginseng, not because it is pan of the ginseng family but to suggest energy-promoting and stress-reducing benefits similar to those attributed to the more well-known Asian and Siberian ginsengs. Although there has been very little human research done on ashwagandha, herbalists and natural medicine practitioners often recommend the herb to combat stress and fatigue, and it does appear to be particularly suited as a relaxant following stressful events.



Although the scientific evidence for the benefits of ginseng and its mechanisms of action can be considered inconclusive, the adaptogenic role of the various ginseng strains have proven beneficial for many thousands of years and may therefore prove valuable as normalizing substances during stressful conditions.



The active components in Panax ginseng and American ginseng are thought to be a family of triterpenoid saponins that are collectively referred to as ginsenosides. In general, most of the top-quality ginseng products, whether whole root or extract, are standardized for ginsenoside content. The active components in Siberian ginseng are considered to be a group of related compounds called eleutlierosides. It has been theorized that ginseng's action in the body is the result of its interaction within the hypothalamic-pituitary axis to balance secretion of adrenal corticotropic hormone (ACTH). ACTH has the ability to bind directly to brain cells and can affect a variety of stress-related processes in the body. These behaviors might include motivation, vitality, performance, and arousal.



In a widely cited, though poorly conducted, study of student nurses on night duty, 1,200 mg/day of Panax ginseng appeared to improve general indices of stress and mood disturbances (Coleman et al,, 2003). Levels of free fatty acids, testosterone, and blood sugar, which were all elevated by night work, were significantly reduced to the levels observed under day work. In another study, 2,700 mg/day of Panax quinquefoUus was able to reduce blood sugar levels and insulin requirements in a group of diabetic subjects following 3 months of supplementation (Vuksan et al., 2000). One study of the effects of 200 mg/day of Panax ginseng extract for 12 weeks showed improvements over baseline values of mental performance: attention, mental processing, logical deduction, and both motor function and reaction time (Kennedy and Scholey, 2003).



Over a period of several decades, German and Soviet researchers have studied the effects of ginseng extract, typically standardized to 4% ginsenosides, on the performance of athletes. One study compared 200 mg/day of eleuthero versus a placebo in 14 highly trained male athletes (Dowling et al., 1996). The ginseng group showed an increase in maximum oxygen uptake compared with the placebo group as well as a statistically significant improvement in recovery time and lower serum lactate values. Other studies in various groups of young athletes have shown ginseng extract to provide statistically significant improvements in performance measures, such as forced vital capacity and maximum breathing capacity, compared with the placebo groups (Pieralisi et al., 1991; Ziemba et al., 1999).



In a double-blind, placebo-controlled, crossover study (8 weeks on treatment, 2 weeks of washout, and 8 weeks on treatment), 45 patients were given 900 mg of ginseng 3 times a day. Mean International Index of Erectile Function scores were significantly higher in patients treated with the ginseng than those who received a placebo. The authors concluded that ginseng may be an effective alternative for treating male erectile dysfunction (Hong et al., 2002).



An open study consisting of 36 children ranging from 3 to 17 years old were given a combination product containing Panax quinquefolium (200 mg) and Ginkgo ttloba extract (50 mg) to be taken twice daily for 4 weeks. At the beginning of the study, after 2 weeks, and then at week 4, parents completed the Conners' Parent Rating Scale. After 4 weeks of treatment, the proportion of subjects exhibiting improvements ranged from 44% for the social problems attribute to 74% for the Conners' attention-deficit/ hyp era ctivity disorder (ADHD) index and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-JV) hyperactive-impulsive attribute. The authors concluded that the combination treatment may improve symptoms of ADHD and that further research on the combination should be done (Lyon et al., 2001).



Unfortunately, the scientific evidence for ginseng is far from definitive. For every study showing a positive benefit in terms of energy levels and/ or physical or mental performance, there is at least one other study showing no benefits (Bahrke and Morgan, 2000). Part of the discrepancy in results from well-controlled studies may have to do with differences among the ginseng extracts used in various studies (nonstandardized extracts with unknown quantities of active components).

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Brewer's Yeast Supplements

Brewer's yeast is not the same as the baker's yeast that makes bread rise or the yeast that causes yeast infections. It is just what it sounds like it should be the yeast used in making beer. Because of the different methods used in its culture, it can vary in its nutritional profile; however, it tends to be a good source of several B vitamins and a few minerals: thiamin (B,), riboflavin (B2), niacin (B3), folic acid, pyridoxine (Bfi), B12, chromium (known as glucose tolerance factor [GTF]), copper, iron, and zinc.



Most of the clinical work that has been performed on brewer's yeast has been for its potential use as a source of organic chromium, which has been theorized and confirmed in several studies to improve glucose cohtrol and lipid values. It is this application that has led to claims about brewer's yeast being good for reducing blood sugar and cholesterol. One study suggests its beneficial role in athletic recovery. The energy claims made on brewer's yeast are yet unfounded by clinical research.



One product made from brewer's yeast that is not included in this review is called brewer's yeast cell wall. It is a byproduct of producing brewer's yeast extracts and is being promoted as a functional food for modulating the immune system, controlling cholesterol, and promoting healthy intestinal flora (Tomohiko et al, 2000, 2001).



AcneWeber et al. (1989) studied the effects of a maximum of 5 months of brewer's yeast supplementation (Saccharomyces cerevmae Hansen CBS 5926 [Perenterol]) in 139 patients with acne. Physicians' rating of the results on the treatment group was very good or good in 74% of the patients versus 21.7% in the placebo group. In the treatment group that was rated very good or good, 80% of the patients were considered healed or very much better compared with only 26% of the placebo group that was rated very good or good.



Athletic Recovery and Antioxidant

In a nonblinded, controlled study, the effect of an undefined yeast cell preparation (high in antioxidant vitamins, antioxidant enzymes, trace elements, and minerals) on the stress reaction and antioxidant status of nine highly trained athletes was studied. Venous blood samples were drawn and tested in the resting state after an overnight fast followed by a 15-km cross-country race. The treatment with the yeast cell preparation gave an improvement in the systemic and muscular stress reaction, reflected by a lower soluble interleukin-2 receptor and plasma fibrinogen and higher plasma fibronectin in the resting state, and a significant difference in fibrogen and fibronectin 1 hour after the race. Myoglobin, CKMM3, and mangan superoxide dismutase were reduced, reflecting a decrease in free-radical stress (Konig et al., 1999).



Blood Sugar and Diabetes

The effect of daily chromium supplementation (either brewer's yeast containing 23.3 u.g of chromium, or carbon tetrachloride providing 200 u.g of chromium) was tested on glucose tolerance, serum lipids, and drug dosage in 78 type 2 diabetes patients. The study was a double-blind, placebo-controlled, crossover design that lasted 32 weeks. The authors concluded that the supplementation with chromium resulted in better control of glucose and lipid variables, with decreases of drug dosages (to the point that some subjects no longer needed insulin). The brewer's yeast supplementation of chromium increased the time chromium was retained in the body and extended the beneficial effects as a result.



The effect on serum glucose and lipids of brewer's yeast supplementation (10 g/day for 12 weeks) was studied in a controlled (torula yeast) study of 22 Chinese adults. Blood was drawn before the glucose load and at 30-, 60-, 90-, and 120-minute intervals after. The treatment group resulted in decreases in serum triacylglycerol values and in 60- and 90-minute values of oral glucose tolerance testing (Li, 1994).



Rabinowitz et al. (1983) studied the effect of chromium supplementation on carbohydrate utilization in a double-blind, random, crossover trial involving 43 men. This study was conducted because of the observation of diabetes resulting from chromium deficiency in experimental animals and humans during long-term parenteral nutrition. The groups were given either inorganic chromium (chromium trichloride), a brewer's yeast containing GTF (an organic form of chromium), a brewer's yeast not containing GTF, or a placebo. The patients were further split into subgroups of 21 ketosis-prone men, 7 ketosis-resistant nonobese men, and 15 ketosis-resistant obese men. Chromium levels were found to increase In the body pools of the men from treatment with either organic or inorganic forms of chromium by about 25%. Additionally, in the ketosis-resistant subgroups, there was a significant increase in postprandial insulin from treatment with brewer's yeast that contained GTF. No effects were found, however, on carbohydrate metabolism in any of the groups.



In one study of 23 elderly people, the effect on glucose tolerance, insulin, cholesterol, and triglycerid.es of 200 jig of chromium (from chromic chloride), 5 g of brewer's yeast, or placebo supplementation was studied. After 10 weeks, no differences were found among the groups on the measured parameters. Plasma chromium content, however, rose after the supplementation with chromic chloride, but not with brewer's yeast. The authors concluded that age was not a factor leading to chromium deficiency.



Saner etal. (1983) conduced a study of the effect of chromium supplementation (with 30 g/day of brewer's yeast containing 50 iig of chromium) for S weeks on patients with Turner syndrome, which is characterized by a high incidence of diabetes. Chromium- and lipid-value testing suggested that the study patients had chromium deficiencies and that these deficiencies could have a role in the abnormal glucose tolerance tests found in many Turner syndrome patients.



In a small pilot study involving 10 patients with type 2 diabetes, the effect of brewer's yeast supplementation was studied. Eight of the 10 patients showed improvement in glucose tolerance. No significant changes in serum insulin, total cholesterol, or triglycerides were found (Bialkowska etal., 1981).



Glucose control and lipid values were compared after the daily ingestion of either 9 g of chromium-rich brewer's yeast or chromium-poor torula yeast for 8 weeks. The 24 participants in the study were older (mean age of 78 years) and were divided into normal and diabetic subgroups. In the brewer's yeast group, glucose tolerance improved significantly and insulin output was reduced after supplementation. Additionally, cholesterol and total lipids fell after supplementation in this group, with higher decreases in the hypercholesterolemic people. The torula yeast group showed no significant changes in glucose control, insulin, or lipids. Cholesterol was found to have significantly decreased in the subgroup of nondiabetics but not in the diabetic group.



Cardiovascular Health

A review of yeast-derived fiber products has suggested that they are a heller source of fi-glucan (a dietary fiber) than are oat products because they are more concentrated; therefore, yeast products may be better dietary additions to lower serum cholesterol levels (Bell et ah, 1999). Apart from being a E-glucan source, brewer's yeast and chromium is known to improve blood lipid values, cholesterol, and triglycerides. Several of these studies have been cited here.



It is important to look at the nutritional content of the brewer's yeast product to verify that it contains GTF (or chromium) if its intended use is for chromium supplementation. Some people report mild gastrointestinal (GI) upsets when first taking brewer's yeast. Starting with small amounts (1/4 teaspoon daily) and increasing as desired (to 1-3 tablespoons daily) can help patients avoid GI upsets. In clinical studies for blood sugar control, from 5-30 g of GTF-containing brewer's yeast was taken daily with beneficial results. No other serious side effects have been noted.

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Bee Product Supplements

Bee products commonly used as dietary supplements are bee pollen, propolis, and royal jelly. They are all included in one review because they contain many overlapping constituents and claims and are often used in formulalioris together, making them difficult to narrowly define in terms or" content.



Bee pollen is difficult to characterize specifically because products sold as "bee pollen" are made up of a variable content of vitamins, minerals, ami.no acids, carbohydrates, and trace minerals. The plants the pollen was harvested from and under what conditions also vary. Typical claims for bee pollen include use as an energizer and for athletic endurance, although clinical studies are lacking to confirm these claims.



Royal jelly is the food the worker bees bring to fortify the queen bee, and it is fed to bee larvae in their first few days of life. It is a secretion that comes from the head of the worker bee and contains flower nectar, sugars, and proteins. As an overall tonic and energizer, royal jelly is generally used for people who need something to make them thrive and feel younger.



Propolis, sometimes called "nature's penicillin," is a complex mixture of mostly pollen and waxes that bees collect from plants and then use to sterilize, cement, and varnish the hives. It is rich in amino acids, trace minerals, flavonoids, and vitamin K. Although in preclinical studies propolis has been confirmed to be effective as an antibacterial, anti-fungal, and anti-inflammatory, clinical studies are needed to confirm these roles and determine the therapeutic dosages and conditions for which it is best suited.



Overall, some evidence exists to support the claims of these bee products, but much more clinical work is needed, and certainly an effort to define and characterize products would help our understanding. Considering the other natural alternatives with more clinical substantiation that exist for many of the claims of propolis, it may be best to limit the use of propolis unti! further clinical work is performed. The most exciting and promising uses seem to be as an alternative antibiotic and to treat inflammation, especially considering the negative issues that exist for drugs on the market in those categories and the apparent lack of serious negative side effects with bee products (in nonallergic persons).



PREMENSTRUAL SYNDROME. In a randomized, double-blind, placebo-controlled, crossover trial, a preparation (Femal) composed of bee pollen extract, pollen and pistil extract, and royal jelly was tested in women with PMS. During 2 months of treatment, the efficacy of the Femal preparation was tested with well-established questionnaires and daily measurements of body weight. Overall symptom scores were reduced significantly in the treatment group, and the authors noted evidence of a slow onset of benefits to treatment. PMS-related weight iMin was reduced by 50% by treatment compared with placebo. No adverse effects were reported in the study (Windier and Christer, 2002).



ATHEROSCLEROSIS. A statistical review on the published human and ciinical studies involving royal jelly estimated that the use of 50-100 mg royal jelly daily could reduce total serum cholesterol levels by 1.4% and total serum Jipids by about 10%.



MALNUTRITION. In an uncontrolled clinical trial, royal jelly {Royal Peking Jelly, 800 mg dai ly) was given to patients with malnutrition secondary to various diseases. Through clinical and biochemical evaluation, promising results were found with respect to body weight, gut proteins, plasma aldoslerone concentration, and nitrogen balance (Foppiani, 1984).



HERPES. Three groups of 30 people with herpes simplex virus (HSV) type 2 participated in a study comparing propolis to acyclovir and placebo in a randomized, masked-investigator, controlled, multicenter clinical study. Treatment began in the blister phase (ointment was applied 4 times daily topically to blisters, or inserted on tampons if the blisters were vaginal or on the cervix), and the participants were examined at days 3, 7, and 10 of treatment The clinical symptoms and the number and size of blisters were recorded. The healing process was found to be faster in the propolis group, with the number of patients healed on day 10 being 24, 14, and 12, and the number of patients healed on day 7 being 10, 4, and 3 out of 30 in the propolis, acyclovir, and placebo groups, respectively. In addition, among the women with vaginal infections of microbial pathogens, propolis was found to normalize vaginal flora in 55% of the women, while the acyclovir and placebo groups had no effect. Propolis was also found lo be more effective at reducing local symptoms (Vynograd et al., 2000).



IMMUNE STIMULATION. The immune-stimulating effect of a prophylactic propolis treatment was studied in an open prospective clinical study. Propolis XNP was given (500 mg in the morning for 13 days), and cytokine secretion capacity was studied during and after treatment. The cytokine secretion capacity (but not the cytokine plasma levels) increased significantly during the treatment period in a time-dependent manner. The authors concluded that propolis was able to elicit an enhanced immune reactivity without side effects (Bratter et al., 1999).



INFLAMMATORY RESPIRATORY DISEASE, An aqueous propolis extract (Nivcrisol) was studied for the treatment of chronic inflammatory diseases of the upper airways in preschool and school children during the cold season of 1994-1995. Beneficial results found for the propolis extract include decreased numbers of acute and chronic symptoms and a decrease or suppression of the viral-microbial flora in the upper airways. The authors concluded that the propolis extract preparation was a good adjuvant medication for the treatment of some forms of acute or chronic rhinopharyngeal diseases, because they found good clinical results and the preparation was well tolerated and economical.



PERIODONTOPATH1ES. Propolis has been found beneficial in the treatment of gingivitis and oral ulcers in several small case studies and pilot clinical studies (Coranov et al., 1979; Magro-Filho and de Carvalho, 1994; Martinez Silveira et al., 1988; Mitroi et al., 1987; Neumann et al., 1986; Schmidt et al., 1980). In addition to their use in treating periodontopathies, preparations with propolis have been found to be antimicrobial, anti-inflammatory, and highly antimycotic (against Candida albicans] and to have antiscar effects (Gafar et al., 1989; Kosenko and Kosovich, 1990; Vitoria el al., 1999).



GIARDIASIS. In a study of propolis extract ("bee glue" or Propolisina) for the treatment of giardiasis, 138 people were divided into two groups and given either propolis or an imidazole derivative (tinldazole), The propolis extract treatment resulted in a 52% cure in children using a 10% concentrated extract and a comparable efficacy in adults with a 20% concentrated extract. In adults who undertook treatment with a 30% concentrated extract, there was higher efficacy than tinidazolc (60% versus 40%, respectively). The authors concluded it to be a good treatment that is economical, which is important for people in developing countries.

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Georgiy Kharchenko - herbal weight loss, synephrine fat burners, phentramin d diet pills