Search PubMed⌕ Search

Biomedical subjects

Vladimir Vuksan

Publications and source records attributed to Vladimir Vuksan.

16 recordsLinked to original sources

Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety.

BACKGROUND AND AIM: To address the paucity of randomized clinical studies assessing ginseng on long-term outcomes in type 2 diabetes, we assessed the clinical antidiabetic efficacy and safety of 12 weeks of supplementation with a Korean red ginseng (KRG) preparation, dose, and mode of administration, selected from an acute, clinical, screening model. METHODS AND RESULTS: Nineteen participants with well-controlled type 2 diabetes (sex: 11 M:8 F, age: 64+/-2 years, BMI: 28.9+/-1.4 kg/m(2), HbA(1c): 6.5%) completed the study. Using a double-blind, randomized, crossover design, each participant received the selected KRG preparation (rootlets) and placebo at the selected dose (2 g/meal=6 g/day) and mode of administration (preprandial oral agent [-40 min]) for 12 weeks as an adjunct to their usual anti-diabetic therapy (diet and/or medications). Outcomes included measures of efficacy (HbA1c and fasting- and 75-g oral glucose tolerance test [OGTT]-plasma glucose [PG], plasma insulin [PI], and insulin sensitivity index [ISI] indices); safety (liver, kidney, haemostatic, and blood-pressure function); and compliance (returned capsules, diet-records, and body-weight). There was no change in the primary endpoint, HbA(1c). The participants, however, remained well-controlled (HbA1c=6.5%) throughout. The selected KRG treatment also decreased 75 g-OGTT-PG indices by 8-11% and fasting-PI and 75 g-OGTT-PI indices by 33-38% and increased fasting-ISI (homeostasis model assessment [HOMA]) and 75 g-OGTT-ISI by 33%, compared with placebo (P<0.05). Safety and compliance outcomes remained unchanged. CONCLUSIONS: Although clinical efficacy, as assessed by HbA1c, was not demonstrated, 12 weeks of supplementation with the selected KRG treatment maintained good glycemic control and improved PG and PI regulation safely beyond usual therapy in people with well-controlled type 2 diabetes. Further investigation with similarly selected KRG treatments may yield clinical efficacy.

Administration, Oral↗

Long-term intake of North American ginseng has no effect on 24-hour blood pressure and renal function.

Ginseng is consumed by 10% to 20% of adults in Asia and by up to 5% in Western countries. Despite observational evidence suggesting a link between its intake and the development of hypertension, there remains no long-term scrutiny for its effect on blood pressure (BP). We therefore undertook a randomized, placebo-controlled, double-blinded, crossover trial in 52 hypertensive individuals to determine the effect of 12-week North American ginseng intake on 24-hour BP; we also measured serum cystatin C as a marker of renal function. After a 4-week placebo run-in, we randomly assigned 52 participants to 3 g/day of ginseng or placebo for 12 weeks. This was followed by an 8-week washout and a subsequent 12-week period in which the opposite treatment was administered. At run-in and at weeks 0 and 12 of each treatment period, participants were fitted with an ambulatory BP monitor to assess 24-hour BP. The primary outcome was the treatment difference at week 12 in mean 24-hour systolic BP. Secondary outcomes were treatment differences at week 12 in other ambulatory BP parameters and serum cystatin C. Forty participants (77%) completed the trial, with 3 removed from main analysis (n=2, antihypertensive drug changes; n=1, incomplete ambulatory monitoring). In the remaining 37, 12-week ginseng treatment was associated with a neutral effect on all ambulatory BP parameters compared with placebo; an intention-to-treat analysis supported this. Ginseng did not affect serum cystatin C level. Overall, long-term ginseng use had no effect on 24-hour BP and renal function in hypertensive individuals.

Blood Pressure↗

Korean red ginseng rootlets decrease acute postprandial glycemia: results from sequential preparation- and dose-finding studies.

BACKGROUND: Fractionation of a ginseng source to produce differences in the ginsenoside profile might influence its effect on postprandial glycemia. To explore this possibility and identify an efficacious ginseng for a longterm study, we conducted a preparation-finding study of different Korean red ginseng (KRG) root fractions followed by a dose-finding study of the most efficacious fraction. METHODS: A double-blind, randomized, within-subject design was used in both studies. In the preparation-finding study, 7 healthy subjects (sex: 3m:4f, age: 32 +/- 4 y, BMI: 24 +/- 2 kg/m2) received 6 g placebo and KRG-rootlets, -body, and -H2O extract 40 min before a 50 g-OGTT with finger-prick blood samples at -40-, 0-, 15-, 30-, 45-, 60-, 90-, 120-min. In the dose-finding study, 12 healthy subjects (sex: 9M,3F, age: 29 +/- 3 y, BMI: 22.5 +/- 1 kg/m2) received 0 g (placebo), 2 g, 4 g, and 6 g of the most efficacious root fraction following the same protocol. Ginsenosides were analyzed using HPLC-UV. RESULTS: In the preparation-finding study, a wide variation in the ginsenoside profiles was achieved across the 3 KRG fractions. This variation coincided with differential effects. The main effects of KRG-rootlets (p = 0.050) and time (p < 0.001) and their interaction (p < 0.1) were significant. This was reflected in a 29% reduction in area under the curve (AUC) by KRG-rootlets compared with placebo (p = 0.052). Conversely, neither KRG-H2O extract nor KRG-body affected glycemia. Stepwise-multiple regression models identified Rg1 as the sole predictor of mean- and AUC postprandial blood glucose. In the dose-finding study, KRG-rootlets were tested as the most efficacious fraction. A significant effect of KRG-rootlets treatment (mean of 3 doses) but not dose was found. The mean of 3 doses decreased AUC by 17% compared with placebo (p = 0.057). CONCLUSIONS: Together the studies indicate 2 g KRG-rootlets is sufficient to achieve reproducible reductions in postprandial glycemia. But the longterm sustainability of KRG selected using this approach remains to be tested.

Adult↗

North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension.

An early observational study suggested that ginseng could elevate blood pressure. This caused concern because 4.5% of American adults use ginseng, with a popular choice being North American ginseng. To date, North American ginseng lacks hemodynamic evaluation; therefore, we conducted a randomized, double-blinded, controlled trial to investigate its effect on blood pressure in 16 hypertensive individuals (mean+/-SD age 61.1+/-8.1 years; systolic/diastolic blood pressure 132.4+/-12.8/83.3+/-8.1 mm Hg; 13 on antihypertensives). We used 6 batches of North American ginseng root that varied in quality and ginsenoside content, representing the spectrum of this ginseng on the market. On 8 mornings, each participant was fitted with an ambulatory blood pressure monitor, which measured blood pressure during a 30-minute baseline period. Each participant then consumed in a randomized and double-blind fashion 3 g of encapsulated treatment: placebo (on 2 mornings) or powdered North American ginseng (on 6 mornings). After treatment, blood pressure was measured every 10 minutes for 160 minutes, and its change at each post-treatment time point relative to baseline was determined per individual and averaged, and the mean was obtained for the overall 160-minute period. None of the North American ginsengs or their mean differed from placebo in their effect on overall (160 minutes) mean blood pressure change. None affected blood pressure versus placebo at the 10-minute intervals; but their mean versus placebo increased systolic and diastolic blood pressure at 140 and 160 minutes, respectively, and lowered diastolic blood pressure at 100 minutes. The findings together suggested that North American ginseng exerts a neutral acute effect on blood pressure in hypertensive individuals.

Aged↗

Herbal remedies in the management of diabetes: lessons learned from the study of ginseng.

The only example of an approved antidiabetic drug that was developed from a herbal source with a long history of use for diabetes is the biguanide Metformin from French lilac (Galega officinalis). Clinical data are beginning to emerge that support antidiabetic indications for several other herbs. This viewpoint discusses the state of the evidence for their clinical antidiabetic efficacy. One of the most studied herbs, ginseng (Panax spp.), is used as a model to illustrate the challenges associated with achieving reproducible clinical efficacy. It is concluded that the best evidence for clinical efficacy in diabetes remains for ginseng. But overall insufficient evidence exists to claim a diabetes indication for herbs. The experience with ginseng suggests that although reproducible efficacy may be achieved using an acute postprandial clinical screening model to select an efficacious ginseng batch, dose, and time of administration, there is a need to develop a basis for standardization that ties the composition of herbs to efficacy. In absence of such standardization, the use of herbs in diabetes must be approached cautiously.

Complementary Therapies↗

Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians.

BACKGROUND: Few studies have evaluated the associations of plasma homocysteine concentration, the methylenetetrahydrofolate reductase (MTHFR) C677T genotype and B vitamin concentration with intima media thickness (IMT) in multiethnic populations. METHODS: In the Study of Health Assessment and Risk in Ethnic groups (SHARE), we measured carotid IMT, fasting serum folate, serum B12, plasma pyridoxal-5'-phosphate (PLP) and plasma homocysteine and determined the MTHFR C677T genotype in a cross-sectional study of 818 South Asian, Chinese and European Canadians without previous history of CVD, cancer or diabetes during 1996-1998. RESULTS: Plasma homocysteine was inversely related to serum folate, serum B12, plasma PLP, B vitamin supplement use and Chinese ethnicity, and was positively associated with hypertension, smoking, IMT, MTHFR 677T/T genotype and South Asian ethnicity. Although ethnicity was not a statistically significant modifier, among carriers of the MTHFR 677T/T genotype with serum folate < or =14 nmol/L compared to >14 nmol/L, plasma homocysteine was significantly higher among South Asians (50.9% increase, P < 0.001) and Europeans (52.4% increase, P < 0.001) but not Chinese (11.0% increase, P > 0.05). Plasma homocysteine > 11.7 micromol/L was associated with a 5.9% (95% CI: 1.9%, 10.0%) increase in IMT (approximately 0.04 mm) in the pooled-data analyses with similar increases noted in the ethnic-specific analyses. The 677T/T genotype was not associated with a significant change in IMT in the pooled-data analyses (2.7%; 95% CI: -1.7%, 7.2%) nor in ethnic-specific analyses compared to other genotypes, although there were only 63 677T/T homozygotes. CONCLUSION: The combination of lower serum folate and the MTHFR 677T/T genotype is associated with increased plasma homocysteine among South Asians and Europeans, but the association is not evident among Chinese possibly because their serum folate may not have been low enough to compromise MTHFR activity. Plasma homocysteine > 11.7 micromol/L appears to be associated with a clinically important increase in IMT.

Asia, Southeastern↗

Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides.

BACKGROUND: It is unclear whether other ginseng sources can replicate the glycemic-lowering efficacy observed previously with American ginseng and whether ginsenosides are mediators. We assessed the effect of eight popular ginseng types on postprandial plasma glucose (PG) and insulin (PI) indices, linking effects to ginsenoside profiles. METHODS: Using a double-blind, randomized, multiple-crossover design, 12 healthy participants (gender: 6M:6F, age: 34 +/- 3 y, BMI: 25.8 +/- 1.2 kg/m(2)) received 10 3g treatments: American, American-wild, Asian, Asian-red, Vietnamese-wild, Siberian, Japanese-rhizome, and Sanchi ginsengs and two placebos. Each treatment was given 40-minutes before a 75g-oral-glucose-tolerance-test (75g-OGTT) with blood drawn at -40, 0, 15, 30, 45, 60, 90, 120-minutes. HPLC-UV analysis quantified seven principal ginsenosides. RESULTS: Two-factor analysis showed the main effects of ginseng-type and time were significant for PG and PI, with an interaction for PG (p < 0.05). Subsequent one-factor analysis showed an effect of ginseng-type on 90-min-PG and 90-min-PI (p < 0.05). This was reflected in effects on peak-PG, area under the curve (AUC)-PG and AUC-PI (p < 0.05). But the effect on 90-min-PI and AUC-PI were significant (p < 0.05) only in overweight participants (BMI > 25 kg/m(2), n = 6). Planned comparisons with placebo showed a tendency for American ginseng and Vietnamese ginseng to lower 90-min-PG (p < 0.06), while Asian ginseng raised peak-PG and AUC-PG, American-wild ginseng raised 120-min-PG, and Siberian ginseng raised 90-min-PG, 120-min-PG, and AUC-PG (p < 0.05). Stepwise-multiple-regression assessed the protopanaxadiol:protopanaxatriol (PPD:PPT)-ginsenoside ratio as the sole predictor (p < 0.05) for 90-min-PG (beta = -0.43, r(2) = 0.072), AUC-PG (beta = -0.25, r(2) = 0.06), 90-min-PI (beta = -0.26, r(2) = 0.065), AUC-PI (beta = -0.20, r(2) = 0.04). CONCLUSIONS: Ginseng has variable glycemic effects, in which the PPD:PPT-ginsenoside ratio might be involved. But the low variance explained suggests the involvement of other unmeasured ginsenoside or non-ginsenoside components.

Acute Disease↗

Development and evaluation of cultural food frequency questionnaires for South Asians, Chinese, and Europeans in North America.

We developed three ethnic food frequency questionnaires (FFQs) to characterize the diets of South Asian, Chinese, and European immigrants. FFQs were developed from foods reported in the diet records and recalls of 29 South Asians, 25 Chinese, and 20 Europeans participating in a pilot study from 1995-1996 in Hamilton, Ontario, Canada. The FFQ and a seven-day diet record were then administered to 342 South Asians, 317 Chinese, and 346 Europeans participating in the Study of Health Assessment and Risk in Ethnic groups (SHARE) in three Canadian centers from 1996-1998. For FFQ validation, a subset of these participants completed a second seven-day diet record and second FFQ 8 to 10 months later. The FFQ generally underestimated macronutrient and overestimated micronutrient intake compared with the records. Consumption of most macronutrients was lower among South Asians. Energy-adjusted deattenuated correlation coefficients between the records and second FFQ ranged from 0.32 to 0.73 (South Asians), 0.17 to 0.84 (Chinese), and 0.30 to 0.83 (Europeans). The FFQs generally performed well and will be used to investigate diet-disease relations in SHARE. Lower correlations for dietary fats among Chinese persons (0.17 to 0.31) may be improved with more direct questions on the FFQ regarding brand, type, and amount of oil consumed in stirfry servings.

Asia↗

The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century.

It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.

Animals↗

Null and opposing effects of Asian ginseng (Panax ginseng C.A. Meyer) on acute glycemia: results of two acute dose escalation studies.

OBJECTIVE: We have repeatedly reported that a batch of American ginseng with a specific ginsenoside (glycosidal saponin) profile decreases acute postprandial glycemia. We investigated whether Asian ginseng is able to replicate this glycemia-lowering efficacy in two separate acute dose escalation studies. METHODS: Each study was conducted in a separate sample of 11 healthy subjects (gender: 8M:3F and 6M:5F, age: 29 +/- 2y and 27 +/- 3y, BMI: 28.5 +/- 2.1 kg/m(2) and 26.9 +/- 1.4 kg/m(2)) using a randomized, single-blind, placebo-controlled, multiple-crossover design. Treatments consisted of 0 (placebo), 1, 2, and 3 g of Asian ginseng for the first study and 0 (placebo), 3, 6, and 9 g Asian ginseng for the second study administered 40 minutes before a 75g-OGTT protocol with blood drawn at -40, 0, 15, 30, 45, 60, 90, and 120 minutes. Ginsenosides were analyzed by HPLC-UV. RESULTS: Neither the main effect of pooled-treatment, nor dose, nor either factors interaction with time was significant for incremental plasma glucose and insulin. But the diagnostically and therapeutically relevant two-hour plasma glucose (2h-PG) value was significantly higher for pooled Asian ginseng treatment than placebo (5.46 +/- 0.31 versus 4.99 +/- 0.30 mmol/L, p = 0.050). Ginsenoside analyses showed that the Asian ginseng contained up to 96% lower and sevenfold higher quantities of various ginsenosides and their ratios than our previous efficacious batch of American ginseng. CONCLUSIONS: Asian ginseng showed both null and opposing effects on indices of acute postprandial plasma glucose and insulin. This is in contrast to our findings with American ginseng. One explanation may be the marked ginsenoside differences. Practitioners and consumers should be aware of ginseng's variable effects.

Acute Disease↗

The relationship between dysglycemia and atherosclerosis in South Asian, Chinese, and European individuals in Canada: a randomly sampled cross-sectional study.

OBJECTIVE: Raised glucose levels extending from normal into the diabetic range (dysglycemia) are an emerging risk factor for clinical cardiovascular events. The relationship between dysglycemia and atherosclerosis (AS) in the general population and in different ethnic groups remains controversial. RESEARCH DESIGN AND METHODS: Glucose tolerance, HbA1c, other metabolic risk factors for AS, and carotid mean maximal intimal media thickness were assessed in a random sample of 979 Canadians of South Asian, Chinese, and European descent. RESULTS: The age and sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase in HbA1c in all participants (P < 0.0001) and in those of South Asian (P = 0.018), Chinese (P = 0.002), and European (P < 0.0001) descent. This progressive curvilinear relationship was most apparent at HbA1c levels >5.7%. The HbA1c-AS relationship persisted after adjustment for ethnicity, age, sex, diabetes status, abdominal obesity, insulin resistance, insulin secretion, fasting free fatty acids, blood pressure, and/or dyslipidemia (P < 0.004). Both diabetes (P = 0.002) and HbA1c (P < 0.0001) were determinants of the intimal medial thickness when included in separate statistical models. When included together in a single model, HbA1c (P < 0.0001) but not diabetes (P = 0.6) was a significant determinant. CONCLUSIONS: The degree of AS is related to the level of HbA1c irrespective of diabetes status and independent of abdominal obesity and other markers of the metabolic syndrome. This progressive relationship between HbA1c and AS was observed within different ethnic groups.

Adult↗

High-complex carbohydrate or lente carbohydrate foods?

Current dietary guidelines of the American Diabetes Association emphasize the importance of minimizing risk factors for cardiovascular disease while maximizing diabetes control. Potential advantages are seen for increased monounsaturated fat intake, but only the quantity rather than the quality of the carbohydrate is considered important. However, review of the carbohydrate issue suggests that many cultures now at high risk of diabetes originally consumed starchy staples higher in fiber and with a lower glycemic index than eaten currently. Furthermore, diets high in cereal fiber have been associated with improved glycemic control, and low glycemic index diets resulted in reduction in glycosylated proteins in type 1 and 2 diabetes. Finally, large cohort studies have demonstrated beneficial effects of cereal fiber and low glycemic index carbohydrate foods in reducing the risk both for diabetes and cardiovascular disease. The effect of insoluble cereal fiber is not readily explained, but a low glycemic index may result from a slower rate of carbohydrate absorption. Increased meal frequency as a model for reducing the rate of carbohydrate absorption has been shown to reduce day-long glucose and insulin levels in type 2 diabetes and reduce serum lipids in nondiabetic subjects. Therefore, there appears to be a potential role for low glycemic index, high-cereal fiber foods for prevention and treatment of diabetes. Both the nature of the dietary fat and the carbohydrate should be considered as potentially modifiable factors that together with weight control and exercise may play a role in diabetes and cardiovascular disease prevention and treatment.

Carbohydrates↗

Soluble fiber intake at a dose approved by the US Food and Drug Administration for a claim of health benefits: serum lipid risk factors for cardiovascular disease assessed in a randomized controlled crossover trial.

BACKGROUND: The US Food and Drug Administration (FDA) approved health claims for 2 dietary fibers, beta-glucan (0.75 g/serving) and psyllium (1.78 g/serving), on the assumption that 4 servings/d would reduce cardiovascular disease risk. OBJECTIVE: We assessed the efficacy of this dose of fibers in reducing serum lipid risk factors for cardiovascular disease. DESIGN: Sixty-eight hyperlipidemic adults consumed a test (high-fiber) and a control low-fat (25% of energy), low-cholesterol (<150 mg/d) diet for 1 mo each in a randomized crossover study. The high-fiber diet included 4 servings/d of foods containing beta-glucan or psyllium that delivered 8 g/d more soluble fiber than did similar, unsupplemented foods in the control diet. Fasting blood samples and blood pressure readings were obtained at baseline and weeks 2 and 4, and the subjects' weight was monitored weekly. RESULTS: Compared with the control diet, the high-fiber diet reduced total cholesterol (2.1 +/- 0.7%; P = 0.003), total:HDL cholesterol (2.9 +/- 0.8%; P = 0.001), LDL:HDL cholesterol (2.4 +/- 1.0%; P = 0.015), and apolipoprotein B:A-I (1.4 +/- 0.8%; P = 0.076). Applying the Framingham cardiovascular disease risk equation to the data confirmed a reduction in risk of 4.2 +/- 1.4% (P = 0.003). Small reductions in blood pressure were found after both diets. The subjects reported no significant differences in palatability or gastrointestinal symptoms between the diets. CONCLUSIONS: The reduction in serum lipid risk factors for cardiovascular disease supports the FDA's approval of a health claim for a dietary fiber intake of 4 servings/d. Although relatively small in terms of patient treatment, the reduction in cardiovascular disease risk is likely to be significant on a population basis.

Adult↗

Insulin resistance: concepts, controversies, and the role of nutrition.

Insulin resistance is a prevalent condition, in which insulin loses its normal physiological action. Since people were first classified as insulin resistant over 60 years ago, one of the main discoveries has been that insulin resistance clusters with other risk factors such as obesity, elevated triglycerides, and low high-density lipoprotein cholesterol, increasing cardiovascular disease risk. Although insulin resistance appears to manifest first in the periphery and then in the liver, other sites, such as the brain and the pancreatic &b.beta-cell, may play pathogenic roles. Factors contributing to insulin resistance at these sites include perturbations in free fatty acids, glucose, and hormone-signalling, some of which may be linked to various genetic polymorphisms. Appropriate nutritional treatment for insulin resistance is controversial. Two main approaches are drawn from diabetes recommendations: i) a high-carbohydrate, low-fat, high-fibre diet emphasizing low glycemic-index foods and ii) sharing calories between monounsaturated fat and complex carbohydrate at the expense of saturated fat. Recent interest in insulin resistance has prompted the development of new guidelines. Promising data have also emerged, showing that a high-carbohydrate, high-fibre, low-fat diet plus exercise programs maintained through intensive counselling can decrease diabetes risk by over 40%. Additional research is required to confirm the sustainability of this approach and sort out the determinants of insulin resistance so that more effective nutritional interventions will result.

Blood Glucose↗