Robert E. Canale

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion.

Postprandial oxidative stress in response to dextrose and lipid meals of differing size.

We have recently noted that ingestion of dietary lipid (in the form of heavy whipping cream) leads to greater oxidative stress than dietary carbohydrate (in the form of dextrose), when consumed in isocaloric amounts.ObjectiveIn the present investigation we attempted to replicate our work and also to determine the oxidative stress response to dextrose and lipid meals of two different kilocalorie (kcal) amounts.DesignNine young (22 ± 2 years), healthy men consumed in a random order, cross-over design one of four meals/drinks: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 30 min, 60 min, 120 min, and 180 min post meal. Samples were assayed for glucose, triglycerides (TAG), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Area under the curve (AUC) was calculated for each variable, and a 4 × 5 ANOVA was utilized to further analyze data.ResultsA meal × time effect (p = 0.0002) and a time effect was noted for glucose (p < 0.0001; 30 min > Pre, 1 hr, 2 hr, and 3 hr). The dextrose meals primarily contributed to this time effect. No other effects were noted for glucose (p > 0.05). A meal effect was noted for TAG (p = 0.01; 66 g lipid meal > 75 g and 150 g dextrose meals). No other effects were noted for TAG (p > 0.05). An AUC effect was noted for MDA (p = 0.04; 66 g lipid meal > 75 g and 150 g dextrose meals). A meal × time effect (p = 0.02) and a meal effect was noted for MDA (p = 0.004; 66 g lipid meal > 75 g and 150 g dextrose meals). No time effect was noted for MDA (p = 0.72). An AUC effect was noted for H2O2 (p = 0.0001; 66 g lipid meal > 33 g lipid meal and 75 g and 150 g dextrose meals). A meal × time effect (p = 0.0002), a meal effect (p < 0.0001; 66 g lipid meal > 33 g lipid meal and 75 g and 150 g dextrose meals), and a time effect was noted for H2O2 (p < 0.0001; 2 hr > Pre, 30 min, and 1 hr; 3 hr > Pre). The time effect for H2O2 was primarily influenced by the 66 g lipid meal.ConclusionsThese data indicate that 1) minimal oxidative stress is observed following ingestion of dextrose loads of either 75 g or 150 g, or a lipid load of 33 g and 2) lipid ingestion at 66 g leads to greater oxidative stress than lipid at 33 g or dextrose at either 75 g or 150 g. Hence, in a sample of young and healthy men, only 66 g of lipid (taken in the form of heavy whipping cream) leads to a significant increase in blood oxidative stress, as measured by MDA and H2O2.

Comparison of pre-workout nitric oxide stimulating dietary supplements on skeletal muscle oxygen saturation, blood nitrate/nitrite, lipid peroxidation, and upper body exercise performance in resistance trained men

BackgroundWe compared Glycine Propionyl-L-Carnitine (GlycoCarn®) and three different pre-workout nutritional supplements on measures of skeletal muscle oxygen saturation (StO2), blood nitrate/nitrite (NOx), lactate (HLa), malondialdehyde (MDA), and exercise performance in men.MethodsUsing a randomized, double-blind, cross-over design, 19 resistance trained men performed tests of muscular power (bench press throws) and endurance (10 sets of bench press to muscular failure). A placebo, GlycoCarn®, or one of three dietary supplements (SUPP1, SUPP2, SUPP3) was consumed prior to exercise, with one week separating conditions. Blood was collected before receiving the condition and immediately after exercise. StO2 was measured during the endurance test using Near Infrared Spectroscopy. Heart rate (HR) and rating of perceived exertion (RPE) were determined at the end of each set.ResultsA condition effect was noted for StO2 at the start of exercise (p = 0.02), with GlycoCarn® higher than SUPP2. A condition effect was also noted for StO2 at the end of exercise (p = 0.003), with SUPP1 lower than all other conditions. No statistically significant interaction, condition, or time effects were noted for NOx or MDA (p > 0.05); however, MDA decreased 13.7% with GlycoCarn® and increased in all other conditions. Only a time effect was noted for HLa (p < 0.0001), with values increasing from pre- to post-exercise. No effects were noted for HR, RPE, or for any exercise performance variables (p > 0.05); however, GlycoCarn® resulted in a statistically insignificant greater total volume load compared to the placebo (3.3%), SUPP1 (4.2%), SUPP2 (2.5%), and SUPP3 (4.6%).ConclusionNone of the products tested resulted in favorable changes in our chosen outcome measures, with the exception of GlycoCarn® in terms of higher StO2 at the start of exercise. GlycoCarn® resulted in a 13.7% decrease in MDA from pre- to post-exercise and yielded a non-significant but greater total volume load compared to all other conditions. These data indicate that 1) a single ingredient (GlycoCarn®) can provide similar practical benefit than finished products containing multiple ingredients, and 2) while we do not have data in relation to post-exercise recovery parameters, the tested products are ineffective in terms of increasing blood flow and improving acute upper body exercise performance.

Effects of 1,3-Dimethylamylamine and Caffeine Alone or in Combination on Heart Rate and Blood Pressure in Healthy Men and Women

Abstract Background: The use of 1, 3-dimethylamylamine (geranamine), alone and in combination with caffeine, is becoming widespread within the dietary supplement industry. To our knowledge, no data are available concerning the effects of oral geranamine intake on heart rate (HR) and blood pressure in individuals. Methods: Ten young healthy men and women ingested 1 of 5 conditions on different days using a double-blind, randomized, crossover design. The following were ingested after a 10-hour overnight fast: 250 mg caffeine (C), 50 mg geranamine (G 50 mg), 75 mg geranamine (G 75 mg), 250 mg caffeine + 50 mg geranamine (C + G 50 mg), and 250 mg caffeine + 75 mg geranamine (C + G 75 mg). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and rate pressure product (RPP) were measured pre-ingestion and at 30, 60, 90, and 120 minutes post-ingestion. Plasma norepinephrine (NE) and epinephrine (EPI) were measured pre-ingestion and at 60 and 120 minutes post-ingestion. Results: Heart rate was unaffected by treatment, but blood pressure and RPP were higher with geranamine, generally in a dose-dependent manner. The peak percent change from pre-ingestion in SBP (˜20%), DBP (˜17%), and RPP (˜9%) was noted with C + G 75 mg at 60 minutes post-ingestion. Plasma NE and EPI were relatively unaffected by treatment. Conclusion: We report for the first time that acute ingestion of 1, 3-dimethylamylamine alone and in combination with caffeine results in an increase in SBP, DBP, and RPP without an increase in HR. The largest increase is observed at 60 minutes post-ingestion of C + G 75 mg. These changes cannot be explained by circulating NE and EPI.

Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized, placebo controlled, cross-over study

BackgroundWe have recently reported that the dietary supplement Meltdown® increases plasma norepinephrine (NE), epinephrine (EPI), glycerol, free fatty acids (FFA), and metabolic rate in men. However, in that investigation measurements ceased at 90 minutes post ingestion, with values for blood borne variables peaking at this time. It was the purpose of the present investigation to extend the time course of measurement to 6 hours, and to include women within the design to determine if sex differences to treatment exist.MethodsTen men (24 ± 4 yrs) and 10 women (22 ± 2 yrs) ingested Meltdown® or a placebo, using a randomized, cross-over design with one week separating conditions. Blood samples were collected immediately before supplementation and at one hour intervals through 6 hours post ingestion. A standard meal was provided after the hour 3 collection. Samples were assayed for EPI, NE, glycerol, and FFA. Five minute breath samples were collected at each time for measurement of metabolic rate and substrate utilization. Area under the curve (AUC) was calculated. Heart rate and blood pressure were recorded at all times. Data were also analyzed using a 2 (sex) × 2 (condition) × 7 (time) repeated measures analysis of variance, with Tukey post hoc testing.ResultsNo sex × condition interactions were noted for AUC for any variable (p > 0.05). Hence, AUC data are collapsed across men and women. AUC was greater for Meltdown® compared to placebo for EPI (367 ± 58 pg·mL-1·6 hr-1 vs. 183 ± 27 pg·mL-1·6 hr-1; p = 0.01), NE (2345 ± 205 pg·mL-1·6 hr-1 vs. 1659 ± 184 pg·mL-1·6 hr-1; p = 0.02), glycerol (79 ± 8 μg·mL-1·6 hr-1 vs. 59 ± 6 μg·mL-1·6 hr-1; p = 0.03), FFA (2.46 ± 0.64 mmol·L-1·6 hr-1 vs. 1.57 ± 0.42 mmol·L-1·6 hr-1; p = 0.05), and kilocalorie expenditure (439 ± 26 kcal·6 hrs-1 vs. 380 ± 14 kcal·6 hrs-1; p = 0.02). No effect was noted for substrate utilization (p = 0.39). Both systolic and diastolic blood pressure (p < 0.0001; 1–16 mmHg), as well as heart rate (p = 0.01; 1–9 bpm) were higher for Meltdown®. No sex × condition × time interactions were noted for any variable (p > 0.05).ConclusionIngestion of Meltdown® results in an increase in catecholamine secretion, lipolysis, and metabolic rate in young men and women, with a similar response for both sexes. Meltdown® may prove to be an effective intervention strategy for fat loss, assuming individuals are normotensive and their treatment is monitored by a qualified health care professional.

A 21 day Daniel Fast improves selected biomarkers of antioxidant status and oxidative stress in men and women

BackgroundDietary modification via both caloric and nutrient restriction is associated with multiple health benefits, some of which are related to an improvement in antioxidant status and a decrease in the production of reactive oxygen species. The Daniel Fast is based on the Biblical book of Daniel, is commonly partaken for 21 days, and involves food intake in accordance with a stringent vegan diet. The purpose of the present study was to determine the effect of a 21 day Daniel Fast on biomarkers of antioxidant status and oxidative stress.Methods43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day Daniel Fast following the guidelines provided by investigators. Subjects reported to the lab in a 12 hour post-absorptive state both pre fast (day 1) and post fast (day 22). At each visit, blood was collected for determination of malondialdehyde (MDA), hydrogen peroxide (H2O2), nitrate/nitrite (NOx), Trolox Equivalent Antioxidant Capacity (TEAC), and Oxygen Radical Absorbance Capacity (ORAC). Subjects recorded dietary intake during the 7 day period immediately prior to the fast and during the final 7 days of the fast.ResultsA decrease was noted in MDA (0.66 ± 0.0.03 vs. 0.56 ± 0.02 μmol L-1; p = 0.004), while H2O2 demonstrated a trend for lowering (4.42 ± 0.32 vs. 3.78 ± 0.21 μmol L-1; p = 0.074). Both NOx (18.79 ± 1.92 vs. 26.97 ± 2.40 μmol L-1; p = 0.003) and TEAC (0.47 ± 0.01 vs. 0.51 ± 0.01 mmol L-1; p = 0.001) increased from pre to post fast, while ORAC was unchanged (5243 ± 103 vs. 5249 ± 183 μmol L-1 TE; p = 0.974). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total calorie intake (2185 ± 94 vs. 1722 ± 85).ConclusionModification of dietary intake in accordance with the Daniel Fast is associated with an improvement in selected biomarkers of antioxidant status and oxidative stress, including metabolites of nitric oxide (i.e., NOx).

Hemodynamic and Hematologic Profile of Healthy Adults Ingesting Dietary Supplements Containing 1,3-Dimethylamylamine and Caffeine

Background 1,3-dimethylamylamine (a constituent of geranium), alone and in combination with caffeine, is widely used within dietary supplements. We have recently determined the hemodynamic effects of 1,3-dimethylamylamine and caffeine alone and in combination, using a single ingestion study. However, no study has determined the hemodynamic effects of these ingredients following chronic use. Moreover, no study has determined the effects of these ingredients on bloodborne variables related to health and safety. Therefore, the purpose of this investigation was to assess the hemodynamic and hematologic profile of two different dietary supplements containing 1,3-dimethylamylamine and caffeine (in addition to other ingredients), before and after two weeks of daily intake. Methods 7 men (24.9 ± 4.2 yrs) ingested the dietary supplement Jack3d™, while 4 men and 2 women (22.5 ± 1.8 yrs) ingested the dietary supplement OxyELITE Pro™ once per day for two weeks. On days 1 and 15, resting heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure were measured and rate pressure product (RPP) was calculated. Fasting blood samples were analyzed for complete blood counts, comprehensive metabolic panel, and lipid panel. These tests were done prior to ingestion of supplement. On days 1 and 15 following blood collection, subjects ingested the assigned supplement (2 servings) and HR, SBP, DBP, and RPP were recorded at 30, 60, 90, and 120 minutes post-ingestion. Results After 14 days of treatment, resting HR, SBP, DBP, and RPP were not increased (P > 0.05). No significant changes were noted in any measured bloodborne variable, with the exception of an increase in fasting blood glucose with ingestion of Jack3d™ (P = 0.02). In response to acute intake of the supplements, HR, DBP, and RPP were not increased statistically (P > 0.05). SBP was increased with OxyELITE Pro™ (P = 0.03), but not with Jack3d™ (P = 0.09). Compared to pre-ingestion and in general, both supplements resulted in an increase in SBP, DBP, and RPP from 5%-15%, with a peak occurring at the 60 or 90 minute post-ingestion time. Conclusion Acute ingestion of OxyELITE Pro™, but not Jack3d™, results in an increase in SBP. Chronic intake of two servings per day of OxyELITE Pro™ or Jack3d™ over a 14 day period does not result in an elevation in resting HR, SBP, DBP, or RPP. No significant changes are noted in any measured bloodborne variable following 14 days of ingestion, with the exception of blood glucose with Jack3d™. Longer term intervention studies inclusive of larger sample sizes are needed to extend these findings.

Absence of blood oxidative stress in trained men after strenuous exercise.

UNLABELLED Exercise has been noted in some, but not all, studies to elicit an oxidative stress. The discrepancy in findings may be related to differences in exercise intensity across protocols, as well as to differences in training status of participants. PURPOSE We compared blood oxidative stress biomarkers in exercise-trained men after three different bouts of exercise of varying intensity and duration, as well as a nonexercise condition. METHODS On different days, men (n = 12, 21-35 yr) performed aerobic cycle exercise (60 min at 70% HR reserve) and cycle sprints (five 60-s sprints at 100% maximum wattage obtained during graded exercise testing and ten 15-s sprints at 200% maximum wattage obtained during graded exercise testing). Blood was collected before and 0, 30, and 60 min after exercise and analyzed for malondialdehyde, hydrogen peroxide (H(2)O(2)), advanced oxidation protein products, and nitrate/nitrite (NO(x)). As indicators of antioxidant status, Trolox equivalent antioxidant capacity, superoxide dismutase, catalase, and glutathione peroxidase were measured. RESULTS No differences were noted in malondialdehyde, H(2)O(2), advanced oxidation protein product, or NO(x) between conditions or across time (P > 0.05). Antioxidant capacity was generally highest at 30 and 60 min after exercise and lowest at 0 min after exercise. CONCLUSIONS In trained men, and considering the limitations of the current design (e.g., inclusion of selected oxidative stress and antioxidant biomarkers measured in blood only), strenuous bouts of exercise do not result in a significant increase in blood oxidative stress during the 1-h postexercise period. These findings may be related to attenuation in reactive oxygen species production as an adaptation to chronic exercise training and/or a protective effect of the antioxidant system in response to acute strenuous exercise.

Effect of oral intake of capsaicinoid beadlets on catecholamine secretion and blood markers of lipolysis in healthy adults: a randomized, placebo controlled, double-blind, cross-over study

BackgroundIn the present investigation we compared blood epinephrine (EPI), norepinephrine (NE), free fatty acids (FFA) and glycerol concentrations in response to a capsaicinoid supplement or placebo in healthy adults before and after acute exercise.MethodsTwenty subjects ingested a placebo or supplement (Capsimax™, OmniActive Health Technologies; 2 mg capsaicinoids in a microencapsulated matrix) with one week separating conditions. Fasting blood samples were collected during each visit; 30 minutes following a rest period and before placebo or supplement intake (Pre); 2 hours post intake (2 hr); one minute following the cessation of 30 minutes of exercise performed at 65% of maximal heart rate reserve (2.5 hr); 90 minutes following the cessation of exercise (4 hr). Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were recorded at all times.ResultsA time effect was noted for HR, SBP, and DBP (p < 0.05), with HR and SBP higher at 2.5 hr compared to Pre (due to exercise) and DBP lower at 2.5 hr compared to Pre. No interaction or condition effects were noted for EPI, NE, FFA, or glycerol (p > 0.05). However, a time effect was noted for all variables (p < 0.0001), with values higher than Pre at 2.5 hr for EPI and glycerol, at 2 hr and 2.5 hours for FFA, and at 2 hr, 2.5 hr, and 4 hr for NE (p < 0.05). In terms of percent change from Pre, glycerol was higher with Capsimax™ than for placebo at 4 hr (p = 0.011) and FFA was higher with Capsimax™ than for placebo at 2 hr (p = 0.025) and at 2.5 hr (p = 0.015).ConclusionIngestion of low dose (2 mg) Capsimax™ was associated with an increase in blood FFA and glycerol at selected times post ingestion, as compared to placebo. However, Capsimax™ had no differing effect on EPI or NE compared to placebo. Lastly, no difference was noted in HR, SBP, or DBP between placebo and Capsimax™.

Biochemical and anthropometric effects of a weight loss dietary supplement in healthy men and women.

Background We have recently noted an acute increase in circulating free fatty acids and glycerol, as well as resting metabolic rate, when men and women ingested the dietary supplement OxyELITE Pro™ in a single dose. We have also noted a reduction in appetite when subjects were treated with this supplement for 14 consecutive days. It is possible that such findings may favor body weight and fat loss over time. Therefore, the purpose of the present study was to determine the effects of this dietary supplement on weight loss and associated markers using an eight week intervention. Methods Exercise-trained subjects were randomly assigned in double blind manner to ingest either the dietary supplement (n = 16; aged 22.8 ± 0.7) or a placebo (n = 16; 22.5 ± 0.5) every day for eight weeks. Body weight, body composition, skinfold thickness, serum lipids, and appetite were measured as the primary outcome variables. As measures of supplement safety, a complete blood count and comprehensive metabolic panel were performed, and resting heart rate and blood pressure were measured (pre and post intervention). Results No interactions or main effects were noted for our primary outcome measures (P > 0.05). However, when comparing pre and post intervention values for the supplement, significant decreases were noted in appetite, body weight, body fat percentage, and skinfold thickness (P < 0.05), while increases were noted for total and HDL-C, as well as for resting heart rate (P < 0.05). No changes were noted for placebo from pre to post intervention (P > 0.05), with the exception of an increase in HDL-C (P < 0.05). Blood pressure and bloodborne safety variables were not differently impacted by supplement or placebo (P > 0.05), with the exception of monocytes, for which an interaction effect was noted (P = 0.04). Conclusion These data indicate that the dietary supplement OxyELITE Pro™ may assist in weight and body fat loss in a sample of exercise-trained men and women. The supplement does not result in any adverse effects pertaining to resting blood pressure or bloodborne markers of safety; however a small increase in resting heart rate is observed.