Tapan K. Basu

Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial

Background: Upper respiratory tract infections are a major source of morbidity throughout the world. Extracts of the root of North American ginseng (Panax quinquefolium) have been found to have the potential to modulate both natural and acquired immune responses. We sought to examine the efficacy of an extract of North American ginseng root in preventing colds. Methods: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 323 subjects 18–65 years of age with a history of at least 2 colds in the previous year were recruited from the general population in Edmonton, Alberta. The participants were instructed to take 2 capsules per day of either the North American ginseng extract or a placebo for a period of 4 months. The primary outcome measure was the number of Jackson-verified colds. Secondary variables measured included symptom severity, total number of days of symptoms and duration of all colds. Cold symptoms were scored by subjects using a 4-point scale. Results: Subjects who did not start treatment were excluded from the analysis (23 in the ginseng group and 21 in the placebo group), leaving 130 in the ginseng group and 149 in the placebo group. The mean number of colds per person was lower in the ginseng group than in the placebo group (0.68 [standard deviation (SD) 0.82] v. 0.93 [SD 0.91], difference 0.25%, 95% confidence interval [CI] 0.04–0.45). The proportion of subjects with 2 or more Jackson-verified colds during the 4-month period (10.0% v. 22.8%, 12.8% difference, 95% CI 4.3–21.3) was significantly lower in the ginseng group than in the placebo group, as were the total symptom score (77.5 [SD 84.6] v. 112.3 [SD 102.5], difference 1.5%, 95% CI 1.2–2.0) and the total number of days cold symptoms were reported (10.8 [SD 9.7] v. 16.5 [SD 13.8] days, difference 1.6%, 95% CI 1.3–2.0) for all colds. Interpretation: Ingestion of a poly-furanosyl-pyranosyl-saccharide–rich extract of the roots of North American ginseng in a moderate dose over 4 months reduced the mean number of colds per person, the proportion of subjects who experienced 2 or more colds, the severity of symptoms and the number of days cold symptoms were reported.

Sulfur: its clinical and toxicologic aspects

Although there is no known dietary requirement for inorganic sulfur, it is an essential element for all animal species in as much as they all require the sulfur-containing amino acid methionine. There are three predominate forms of organic sulfur in animals and humans: 1). the thiomethyl of methionine residues in protein; 2). the sulfhydryl disulfides of protein; and 3). the compounds containing ester or amide bound sulfates of glycosaminoglycans, steroids, and many xenobiotic metabolites. Thus, sulfur becomes an important constituent of amino acids, proteins, enzymes, vitamins and other biomolecules. Unlike mammalian species, plants can use inorganic sulfur and synthesize methionine from which are synthesized all the other important sulfur compounds. Hence, sulfur deficiency occurs mainly when plants are grown in sulfur-depleted soils and when humans and animals consume low-protein diets. In recent times, however, the increasing prevalence of refining petroleum and smelting sulfur compounds of metallic minerals into free metals are having a large impact on the balance of sulfur in the environment. Sulfur toxicity is associated mainly with high levels of the element and its toxic volatile substances in the environment. Sulfur dioxide (SO(2)), a major air pollutant, may adversely affect animal and human health by causing bronchitis, bronchoconstriction, and increased pulmonary resistance.

Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats.

Echinacea plant extract is widely used for the prevention and the treatment of upper respiratory tract infections. However, the active components in the herb, their optimal dosages and their in vivo effects are still undefined. Using male Sprague-Dawley rats (425-475 g), an in vivo study was conducted to examine the immunomodulatory effects of various dose levels of three components, isolated and purified from Echinacea purpurea. The components were cichoric acid, polysaccharides and alkylamides. The rats were gavaged orally two times/day for 4 days with three different concentrations of each of the Echinacea components. Among the components, alkylamides at the dose level of 12 microg/kg body weight/day significantly increased the phagocytic activity as well as phagocytic index of the alveolar macrophages. The alveolar macrophages obtained from this group of rats also produced significantly more TNF-alpha and nitric oxide after an in vitro stimulation with LPS than any other active component or the control. None of the components at any concentration had any effect on the release of TNF-alpha, IFN-gamma and IL-2 by the splenocytes. These results suggest that the alkylamides are one of the active constituents of E. purpurea plant. At a dose level of approximately 12 microg/kg body weight/day they effectively stimulate alveolar macrophage function in healthy rats. The immunomodulatory effects of alkylamides appear to be more pronounced in lungs than in spleen.

Efficacy of a standardized echinacea preparation (EchinilinTM) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial

Background:  Recently, echinacea has regained popularity as one of the treatments chosen most commonly by consumers with the expectation that it will reduce the severity and duration of the common cold. However, the results from a limited number of clinical trials for this application have thus far been inconclusive. This incongruity may be the result of investigators utilizing poorly standardized echinacea products, likely devoid of sufficient quantities of active constituents necessary to exert a definitive clinical effect. Therefore, a formulation containing alkamides, cichoric acid, and polysaccharides at concentrations of 0·25, 2·5, and 25 mg/mL, respectively, was prepared from freshly harvested Echinacea purpurea plants (commercially available as Echinilin, Natural Factors Nutritional Products, Inc., Vancouver, BC, Canada). The objective of this study was to test the efficacy of this highly standardized formulation in reducing the severity and duration of symptoms of a naturally acquired common cold.

Echinacea stimulates macrophage function in the lung and spleen of normal rats.

Echinacea plant extract has been used for immunostimulation for many years but the evidence supporting its therapeutic potential is still controversial. Using male Sprague-Dawley rats (425-475 g), an in vivo study was conducted to examine the immunomodulatory effects of preparations of Echinacea containing its components cichoric acid, polysaccharides and alkylamides in different concentrations. The rats were gavaged orally with these preparations, two times/day for 4 days. Phagocytic activity of alveolar macrophage was increased with increasing concentrations of the Echinacea components. A trend of increase in TNF-alpha and nitric oxide release by the alveolar macrophages following an in vitro stimulation with LPS was also evident. An enhanced release of cytokines (such as TNF-alpha and IFN-gamma) in response to Echinacea components, was also apparent in rats spleen macrophage, but at higher concentrations. These results suggest that the Echinacea preparations containing optimal concentrations of cichoric acid, polysaccharides and alkylamides are potentially effective in stimulating an in vivo, non-specific immune response in normal rats.

Vitamin A homeostasis and diabetes mellitus

Recent studies have shown that plasma concentrations of vitamin A (retinol) and its carrier proteins, retinol-binding protein (RBP), and transthyretin (TTR), are decreased in human subjects with insulin-dependent (IDDM) but not with noninsulin dependent diabetes mellitus (NIDDM). Rats made diabetic with streptozotocin (STZ) have also been shown to have reduced levels of plasma vitamin A while its hepatic concentrations elevate. The circulatory vitamin A levels remained low while its hepatic concentrations were further elevated following supplementation of the vitamin. The reduced circulatory status of vitamin A in diabetic animals was not caused by its impaired intestinal absorption. Further experimental studies have pointed to the fact that IDDM is associated with a deficiency of vitamin A, which is secondary to an impaired transport mechanism of this vitamin from its hepatic storage to the target site, such as retina of the eyes. The diabetes-associated changes in vitamin A metabolism were reserved to normal by insulin treatment. The underlying cause for decreased metabolic availability in uncontrolled diabetes, is not clearly understood. It appears that the increased hepatic store of vitamin A is attributed to a decreased availability of its carrier proteins. Subnormal vitamin A status in poorly controlled diabetic subjects may not respond to vitamin A supplementation, rather it may increase its load in the liver leading to hepatoxicity. These results clearly suggest that there is need for further research identifying the importance of vitamin A in diabetes mellitus.

Vitamin A (retinol) status of first nation adults with non-insulin-dependent diabetes mellitus.

OBJECTIVE Poorly controlled insulin-dependent diabetes mellitus (IDDM) has been reported to be associated with an impaired metabolic availability of vitamin A. The purpose of this study was to examine vitamin A status in a select group with non-insulin dependent diabetes mellitus (NIDDM). METHODS Participants included 106 (male, female, > 40 years) Plains Cree adults residing in central Alberta, with NIDDM (n = 59) and non-diabetic controls (n = 47). Non-fasting plasma samples were collected and concentrations of retinol, zinc, alpha-tocopherol, total protein, albumin, retinol binding protein (RBP), transthyretin (TTR), cholesterol, triglycerides, glucose, insulin, and fructosamine were determined. Multiple linear regression was used to identify predictors of plasma RBP concentration. Three repeated 24-hour recalls and a food frequency questionnaire were used to determine vitamin A intakes. RESULTS Diabetic subjects had similar intake and plasma concentration of vitamin A compared to controls. Factors such as alpha-tocopherol, zinc, total protein, albumin, and TTR, which are known to influence vitamin A metabolism, also remained unaffected in subjects with diabetes. Plasma levels of vitamin A carrier protein (RBP), however, were elevated in diabetic subjects, possibly as a result of hyperinsulinemia. The subjects with diabetes had many characteristics of the insulin resistant syndrome, including central obesity, hypertension, and hypertriglyceridemia. Poor metabolic control, based on plasma glucose, was a significant predictor of RBP concentration in diabetic subjects. CONCLUSIONS The plasma concentration of RBP was elevated in diabetic subjects and was associated with normal circulatory availability of retinol. The subjects with NIDDM, characterized by insulin resistance without insulin deficiency, thus, appear to be associated with normal vitamin A status.

DOES BETA-CAROTENE PREVENT CANCER? A CRITICAL APPRAISAL

Abstract The possible role of beta-carotene as a protective nutrient against cancer is reviewed. Human prospective and retrospective studies strongly indicate that beta-carotene protects against lung cancer and probably against stomach cancer. It may also be protective against cancer of the ovary, cervix, breast and other cancers, but not the colon or rectum. The protective factor appears to be beta-carotene itself, rather than total vitamin A. Experiments using a variety of animal models also show that beta-carotene is anticarcinogenic and appears to act at several stages of the process. Possible mechanisms of action are discussed, namely that it must first be converted to vitamin A, that it alters carcinogen metabolism, that it is an anti-oxidant and that it enhances the immune defenses.

Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol)

Using streptozotocin-induced diabetic Wistar rats, studies were carried out to examine the metabolic availability of vitamin A in the plasma, liver and the retina of the eye. Control and diabetic rats were fed ad lib. on a semi-purified diet either with or without (basal) vitamin A supplementation, or pair-fed on the basal diet for 4 weeks. Despite the fact that diabetic rats consumed 48% more feed, they had lower plasma concentrations of retinol (P < 0.003). The decrease in plasma retinol concentration was a response to diabetes (or diabetes-induced trauma), since neither pair-feeding (P < 0.01) nor vitamin A supplementation altered this effect (P < 0.05). Furthermore, the hepatic concentrations of the vitamin in these animals remained elevated and this increase was greater in the supplemented diabetic group (P < 0.001). Decreases in 11-cis retinal (a component of rhodopsin) concentrations in the retina were also observed in diabetic animals. The increased hepatic and the decreased plasma and retina vitamin A levels suggest a defect in the transport of the vitamin from the liver.

Intestinal absorption in health and disease: micronutrients.

The main theme of this chapter concerns the precise biochemical mechanisms involved in stages up to, and including, gastrointestinal absorption of vitamins and certain selected minerals. Essential data regarding sequential events, immediately following absorption of these micronutrients, are also included. There is reference to water-soluble vitamins that are, in general, either coenzymes in various metabolic reactions or carriers of certain biochemical groupings. In contrast, fat-soluble vitamins frequently function as integral components of cell membranes; they, too, receive ample attention. It is appropriate, nevertheless, to recognize that some minerals required in very small amounts are closely allied biochemically with particular vitamins; these specific associations are apportioned emphasis at relevant places in the text. Although predominant discussion centres on the physiological state, clinical reference is necessarily made to gastrointestinal disorders in which imbalance of vitamins and minerals consequently results in an additional detrimental impact on health.