Does 5-hydroxytryptophan cause acute and chronic toxic perturbations in rats?

In 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) occurred in the United States that was attributed to contaminated l-tryptophan (LT). Features of tryptophan-induced EMS included debilitating myalgia and marked peripheral eosinophilia. Although the contaminant(s) was found only in the product produced by a single manufacturer (Showa Denko), all LT was withdrawn from the market and replaced by 5 hydroxytryptophan (5HTP). The belief was that the latter should not contain the implicated contaminant(s), because it was manufactured by a process entirely different from the banished LT. Nevertheless, in 1994 a case diagnosed as EMS appeared. Although the exact causative factor(s) in LT and the possible 5-HTP-induced EMS are uncertain, many reported finding "Peak E" in contaminated LT and the presence of "Peak X" in the 5-HTP of the 1994 case. The latter finding led some to assume that Peak X was a potential pathological agent in 5-HTP that might cause future cases of EMS. To determine whether 5-HTP could cause EMS, we followed 120 male Sprague-Dawley rats, 7 to 8 weeks of age (body weight 200-250 g), for 1 year. They were divided into three groups of 40. One group acted as control, drinking only water; a second group received a low dose of 5-HTP in their drinking water (87.5 mg/dL); and the last group drank a high dose of 5-HTP, 875 mg/dL. No significant differences in the body weights of these three groups of animals were observed over the year. After 2 months, systolic blood pressures (SBP) in the 5-HTP groups were significantly lower for the duration of the study. At the end of 12 months, SBP of the control group averaged 140 mm Hg, the low-dose 5-HTP group averaged 133 mm Hg, and the high-dose group averaged 125 mm Hg. Even though enough 5-HTP was given to cause a physiological response, no significant differences were found in the hematological values, including eosinophil count. Also, no significant differences were found in hepatic and renal values. In the histological studies, no treatment-related changes were noted in the hearts, livers, pancreases, leg striated muscles, and small intestines. In particular, there was no evidence of eosinophilic infiltration and fascial/perimysial inflammation. Accordingly, no significant evidence of EMS was seen in rats receiving high-dose 5-HTP for 1 year.

Effects of Essential Oils and Monolaurin on Staphylococcus aureus: In Vitro and In Vivo Studies.

The antimicrobial properties of volatile aromatic oils and medium-chain fatty acids derived from edible plants have been recognized since antiquity. To give examples, Origanum oil, used as a food-flavoring agent, possesses a broad spectrum of antimicrobial activity due, at least in part, to its high content of phenolic derivatives such as carvacrol and thymol. Similarly, lauric acid, present in heavy concentrations in coconuts, forms monolaurin in the body that can inhibit the growth of pathogenic microbes. Using Staphylococcus aureus in broth cultures and a microdilution method, comparative efficacy of Origanum oil, and a constituent carvacrol, other essential oils and monolaurin were examined. Origanum oil was the most potent of the essential oils tested and proved bactericidal in culture to two strains of Staphylococcus aureus (ATCC #14154 and #14775) at 0.25 mg/mL. In vitro, monolaurin's effects mirrored Origanum oil. The combination of both was bactericidal at the 0.125 mg/mL concentration of each. In two separate In vivo experiments, injected Staphylococcus aureus (ATCC #14775) killed all 14 untreated mice within a 1-week period. In treated mice, over one third survived for 30 days when given oral Origanum oil daily for 30 days (6/14). Fifty percent of the mice survived for 30 days when receiving daily vancomycin (7/14) and monolaurin (4/8). Over 60% of mice survived when receiving a daily combination of Origanum oil and monolaurin (5/8). Origanum oil and/or monolaurin may prove to be useful antimicrobial agents for prevention and therapy of Staphylococcus aureus infections.

Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats.

Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (-)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70-75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (-)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4-6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.

Comparison of Saw Palmetto (extract and whole berry) and Cernitin on prostate growth in rats.

Pharmaceuticals such as finasteride and alpha blockers are used to treat symptoms of benign prostatic hyperplasia (BPH) and are known to cause severe adverse reactions. Accordingly, a search for safer, natural products has been undertaken. Two natural agents (nutraceuticals) have come under recent scrutiny; because natural products, in general, often have evidence of long-term safety. The present study compares the in vivo effects on androgen-induced prostatic enlargement in rats of two nutraceuticals--the widely recognized Saw Palmetto (Serenoa repens) and the less well-known Cernitin (defined pollen extract). Non-castrated rats, had a mean prostate weight of 124 mg +/- 8.8 (S.E.M.) compared to the 24.5 mg +/- 1.9 (S.E.M.) of the castrated rat followed under the same regimen (p < 0.01). When castrated rats were given testosterone, the mass increased significantly to 250.0 mg +/- 31.7 (S.E.M.) (p < 0.01). In the five remaining groups, castrated rats receiving testosterone were given finasteride, an extract of Saw Palmetto, crushed whole berry derived from Saw Palmetto fruit, a water soluble and fat soluble extract of Cernitin or a combination of the Saw Palmetto extract and Cernitin. All treatments decreased the size of the prostate to roughly the same size as in the non-castrated rats, a size that was significantly smaller than castrated rats treated with testosterone in the same manner (p < 0.01). A second study examining non-castrated rats treated with very high doses of testosterone showed similar results. In both studies, the nutraceuticals generally decreased body weight. In conclusion, these studies show the ability of Saw Palmetto (whole berry and extract) and Cernitin to influence prostatic hyperplasia via effects on androgen metabolism.

Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains.

Maitake mushroom has been reported to favorably influence hypertension and diabetes mellitus. The purpose of this study was to compare the effects of whole Maitake mushroom powder and two extracts designated as ether soluble (ES) and water soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and on spontaneously hypertensive rats (SHR), a model of genetic hypertension. In the initial study, we followed four groups of eight ZFR and SHR receiving special diets: a baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD + fraction ES (0.10% w/w), and BD + WS (0.22% w/w). Different effects of these dietary regimens on the 2 rat strains were found. At 35 days, only consumption of the ES diet significantly decreased systolic BP (SBP) in SHR (average 197 vs. 176 mm Hg, p < 0.001), while in ZFR only the groups consuming the whole Maitake and WS diets showed significantly decreased SBP (138 vs. 120-125 mm Hg, p < 0.001). A challenge test with losartan (an angiotensin II receptor blocker) indicates that angiotensin II does not play a major role in SBP regulation of ZFR, but does in SHR where consumption of ES relative to other groups significantly lowered activity of this system. In SHR, glucose, cholesterol, circulating insulin and HbA1C were virtually similar among all dietary groups; but whole Maitake (-22%), ES (-120%) and WS (-80%) diets were associated with decreased triglycerides, and the ES diet with lowered serum creatinine (-29%). In ZFR, circulating insulin and HbA1C were significantly decreased in the whole Maitake powder and ES groups, and tended to be lower in the WS group compared to control. In the ensuing studies, we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg fraction WS plus 100 microg niacin-bound chromium (NBC). Oral gavage of WS clearly lowered SBP and circulating glucose concentrations, more so with the addition of chromium. We conclude that the examined forms of Maitake mushroom have antihypertensive and antidiabetic potential which differ among rat strains. The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin system.

Effects of Maitake mushroom fractions on blood pressure of Zucker fatty rats.

A link exists between insulin resistance and many chronic disorders of aging including advancing-age. A safer means to prevent or, at least, slow the erosion of insulin sensitivity would provide a novel approach to better health. We compared the ability of a specific extract labeled fraction SX, as well as whole Maitake powder, fraction ES and fraction D of Maitake to influence SBP and various pertinent biochemical parameters when given orally to Zucker Fatty rats, a model of insulin resistance and type 2 diabetes mellitus. A secondary gain was the ability to ascertain the effects of bitter melon, olive oil, and sesame oil alone and combined with fraction SX to influence SBP. We found that a water-soluble fraction obtained from Maitake mushroom (SX) lowers SBP and fasting blood glucose significantly over the three to six weeks of study. While whole Maitake fraction lowered SBP effectively, the effects on fasting blood sugar were not apparent under the conditions of study. In contrast to fraction SX and fraction D, developed primarily to enhance immunity and suppress tumor development and growth, has essentially no effect on SBP under the conditions examined. An ether soluble fraction designated ES lowers SBP significantly. Interestingly, olive oil, unlike sesame oil, also lowers SBP. Finally, bitter melon and a combination of SX plus bitter melon also lower SBP. We conclude that fraction SX of Maitake mushroom may be useful to treat insulin resistance alone or combined with other natural products such as bitter melon and niacin-bound chromium.