The Single-dose Absorption and Steady-state Bioavailability of Different Coenzyme Q10 Formulations.

Context: The results for the absorption and bioavailability of different product formulations of Coenzyme Q10 (CoQ10) that are found in the literature are highly variable and confusing to CoQ10 researchers and consumers. Objective: The study intended to measure and compare the single-dose absorption and steady-state bioavailability of three types of Crystal Free (CF) CoQ10 formulations-CF CoQ10, crystalline CQ10, and dry-powder CoQ10. Design: The researcher designed a randomized double-blind laboratory study for the three formulations that was conducted by the same laboratory and investigators and used the same protocol, the same analytical laboratory, and the same methods of analysis. Participants: Participants were matched groups of normal males and females. Outcome Measures: Single-dose absorption and steady-state bioavailability was determined for nine CoQ10 formulations: (1) three formulations of CF CoQ10 in lipid-based softgels, (2) three formulations of crystalline CoQ10 in lipid-based softgels, and (3) three formulations of dry-powder CoQ10 in two-piece, hard gelatin capsules. Plasma profiles were constructed and used to calculate the plasma level at Cmax and the percentage of the dose. From the steady-state bioavailability profiles, the plasma concentrations and the area under the curve (AUC) were determined. From that data, the relationship between the single-dose absorption and the steady-state bioavailability was derived using a linear regression analysis. Results: The single-dose absorption was significantly greater for the CF group compared to that for the crystalline and dry-powder groups (P ≤ .001). The absorption and bioavailability of the crystalline group was significantly greater than that for the dry-powder group (P ≤ .001). For the CF group, the Δ Cmax was 1.83 ± 0.58 ug/ml, the % absorption was 7.03 ± 2.03, the steady-state CoQ10 level was 3.28 ±0.92 ug/ml, and the AUC was 32.80 ± 10.05 ug/ml x days. For the crystalline group, the Δ Cmax was 1.40 ±0.24, the % absorption 3.08 ± 0.53, the steady-state plasma level was 2.50 ± 0.54 ug/ml, and the AUC was 7.55 ± 1.87 ug/ml x days. For the dry powder group, the Δ Cmax was 0.33 ± 0.05 ug/ml, the % absorption was 1.28 ± 0.96 %, the steady-state plasma CoQ10 level was 1.55 ± 0.43 ug/ml, and the AUC was 5.34 ± 1.10 ug/ml x days. The CF formulation's absorption and bioavailability were superior to that of the crystalline and the dry powder formulations. The relationship between the single-dose absorption and the steady-state bioavailability was described by the linear equation y = 1.26 x 1.60. Conclusions: The CF formulation was superior in absorption and steady-state bioavailability compared to the crystalline and dry powder formulations. The linear relationship between the single-dose absorption and the steady-state bioavailability gives an estimate of the steady-state bioavailability in a 24-hour study compared to a longer and more expensive 30-day study.

The Single-dose Absorption of Different CoQ10 Product Types Into the Lymph Compared to That Transported to the Blood.

Context: The science of the metabolism of CoQ10 before and after its absorption into the blood is well known. Almost nothing is known about the absorption of CoQ10 into the lymph. Objective: The study intended to measure and compare the single-dose absorption of three CoQ10 product formulations-crystal-free ubiquinone, crystalline ubiquinol, and a dry-powder ubiquinone-into the abdominal lymph duct as compared to their absorption into the blood circulation. Design: The researcher designed an animal study. Animals: The animals were six large dogs (>50 Kg). Intervention: By gastric gavage, the dogs were given a 100-mg dose of either crystal-free ubiquinone (Q-Best), crystalline ubiquinol (Qunol), or dry-powder ubiquinone, and lymph and venous samples (5 ml) were collected. Outcome Measures: The primary end-point measurements for three CoQ10 product types were the concentration (Cmax), time of Cmax (Tmax), and total CoQ10 absorbed into the lymph and that transported to the blood. Results: Coenzyme Q10 (CoQ10) crystals were found in the dry powder and crystalline ubiquinol formulations. No crystals were found in the crystal-free formulation. Crystals from both the crystalline and dry-powder formulations were found in the small intestine's chyme. After ingestion of a 100-mg dose of CoQ10 formulation, the group mean absorption into the lymph peaked in 2 hours for all three formulations, and the peak appearance (Cmax) in the blood occurred at 6 hours. The absorption was significantly (P ≤ .001) greater for the crystal-free formulation compared to that of the crystalline and dry-powder formulations measured in the lymph and plasma. Conclusions: These data show that the crystal-free formulation's absorption is superior to that found for the other two formulations. These results show that CoQ10 crystals are the causative factor for the poor absorption of CoQ10. The delayed appearance in the blood is due to the slow lymph flow delivering CoQ10 to the blood. The absorption of CoQ10 may not be as poor as described in the literature.

The Instability of the Lipid-Soluble Antioxidant Ubiquinol: Part 2-Dog Studies.

BACKGROUND: Coenzyme Q10 is one of the most widely sold nutritional supplements in the United States. Coenzyme Q10 is available in both its oxidized form (ubiquinone) and its reduced form (ubiquinol). The predominant marketing of Coenzyme Q10 to physicians and patients asserts that the ubiquinol form of Coenzyme Q10 has superior absorption to the ubiquinone form. This study has been designed to compare and contrast the stability and absorption of ubiquinol supplements, as well as the claims made for ubiquinol compared with ubiquinone.Ubiquinol, the reduced state of Coenzyme Q10, is commercially available as a nutritional supplement; however, ubiquinol, by its nature as an electron donor, is much less stable than ubiquinone, the oxidized state of Coenzyme Q10. The absorption, bioavailability and efficacy of ubiquinol products has been much less often tested in clinical trials. Consequently, insufficiently documented marketing claims are being made for ubiquinol supplements. METHODS: In Part 1 of this report on the instability of the lipid-soluble antioxidant ubiquinol, SIBR Research presented data from lab studies showing that oral ubiquinol is likely to be oxidized to ubiquinone and absorbed as ubiquinone. In this Part 2, SIBR Research conducted a study of the transfer and absorption of orally ingested ubiquinol in large dogs. RESULTS: In the dog studies, the percentage of ubiquinol converted to ubiquinone increased as the capsule contents passed through the stomach and small intestines and into the lymph system. CONCLUSIONS: The dog studies demonstrate that oral ubiquinol in commercial nutritional supplements is not stable in the gastrointestinal tract of large dogs. Based on these results, it seems likely that in humans also, most of the ubiquinol from capsules will be oxidized to ubiquinone in the acid profile between the stomach and the small intestines, where there is a wide range of acidity. The ubiquinol from the supplement will be absorbed in the ubiquinone state and will pass into the lymph system as ubiquinone, where it will be reduced back to ubiquinol. It will pass from the lymph system into the blood circulation as ubiquinol.

The Instability of the Lipid-Soluble Antioxidant Ubiquinol: Part 1-Lab Studies.

BACKGROUND: Coenzyme Q10 (CoQ10) is a popular nutritional supplement that is available in both the oxidized and reduced form. The marketing of CoQ10 to physicians often asserts that one form is superior to the other. This study was designed to compare and contrast the stability, absorption and claims made for the reduced form of CoQ10 (ubiquinol) compared with the oxidized form (ubiquinone). There is a need for studies that examine the contents of commercially available ubiquinol products microscopically at room, body and 50°C temperatures. There is also a need for studies of the state of the ubiquinol contents when exposed to a 2.2 pH solution that simulates stomach acidity and an 8.2 pH solution that simulates acidity in the duodenum. METHODS: An investigation of the instability of ubiquinol supplements was conducted via an in vitro study of 13 ubiquinol products marketed in the United States that measured the extent of the conversion of the ubiquinol content to ubiquinone, when the ubiquinol was squeezed out of the capsule at room temperature and when the ubiquinol contents were exposed to a 2.2 pH solution and an 8.2 pH solution. RESULTS: In the in vitro study, the percentage of ubiquinol converted to ubiquinone at body temperature was greatest in the 8.2 pH simulated small intestinal juice: 76%. The percentage of ubiquinol converted to ubiquinone at body temperature in the 2.2 pH gastric juice that simulated conditions in the stomach was 54%. CONCLUSIONS: Ubiquinol in commercial nutritional supplements is fairly stable inside the gelatin capsule but unstable in gastric and small intestine digestive fluids. Based on the data from the lab studies, most of the ubiquinol from the capsule will be converted to ubiquinone prior to reaching the absorption cells in the small intestines. Animal studies are needed to test this hypothesis.

The Instability of the Lipid-Soluble Antioxidant Ubiquinol: Part 3-Misleading Marketing Claims.

BACKGROUND: A lack of understanding of the processes involved in the absorption and transfer of the ubiquinol form of Coenzyme Q10 has led to a situation in which incorrect marketing claims are being made for the absorption of ubiquinol supplements, possibly misleading physicians and patients in the selection of a Coenzyme Q10 supplement for heart health benefits.In clinical trials, the ubiquinone form of Coenzyme Q10 has been associated with significantly improved symptoms and survival in patients with heart failure and significantly improved heart function and reduced cardiovascular mortality in community-living senior citizens. The ubiquinone form is the more stable and more extensively researched form. The ubiquinol form is unstable by virtue of being an electron donor that is easily oxidized to the ubiquinone form. Nevertheless, insufficiently documented marketing claims are being made for ubiquinol supplements. METHODS: To investigate whether or not oral ubiquinol from supplements is absorbed in the ubiquinol form or ubiquinone form, our labs conducted 2 studies of the instability of ubiquinol supplements: a lab study of 13 ubiquinol products sold in the United States and an in vivo study of ubiquinol absorption in large dogs. RESULTS: In the lab study, 76% to 84% of the oral ubiquinol in the nutritional supplements was oxidized to ubiquinone at body temperature in an 8.2 pH solution simulating small intestinal juice. That is to say, much of the oral ubiquinol had been converted to ubiquinone in the sort of pH environment that it would encounter prior to absorption. In a similar fashion, the percentage of ubiquinol converted to ubiquinone increased as the capsule contents passed through the stomach and small intestines of the study dogs. CONCLUSIONS: Based on the data from the lab study and the large dog study, we concluded that ubiquinol in commercial nutritional supplements will most likely be oxidized to ubiquinone before it reaches the absorption cells and that the Coenzyme Q10 in the ubiquinol supplements will be absorbed predominantly in the ubiquinone state, transfer into the lymph nodes predominantly in the ubiquinone state and be reduced back to ubiquinol in the lymphatic system.

Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol(®) on glycemic control of subjects with impaired fasting glucose.

BACKGROUND: This study investigated the efficacy of Diabetinol(®) in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. SUBJECTS AND METHODS: Fifty subjects, aged 18-75 years, with fasting blood glucose ≤15.4 mmol/L, hemoglobin A1c levels ≤12%, and a body mass index between 25 and 40 kg/m(2), were enrolled in a 24-week, randomized, double-blind, placebo-controlled, parallel study. Diabetinol(®) or placebo was administered as 2×525 mg capsules/day. RESULTS: In the Diabetinol(®) group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax) of serum glucose or area under the curve (AUC)0-240 minutes. The time to Cmax was longer for participants on Diabetinol(®) than placebo group at week 12 (P=0.01). Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol(®) group versus placebo. The Diabetinol(®) group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09) and 3.2 mg/dL at week 24 (P=0.41) over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol(®) group. Diabetinol(®) improved 6-month oral glucose tolerance test and 2-hour postprandial glucose profiles in participants between 40 and 60 years of age. CONCLUSION: The current study suggests a role for Diabetinol(®) as an adjunctive therapy for glycemic maintenance and for decreasing the risk of diabetes-associated comorbidities in type 2 diabetic patients on conventional therapies.

Antidiabetic activity of a standardized extract (Glucosol) from Lagerstroemia speciosa leaves in Type II diabetics. A dose-dependence study.

The antidiabetic activity of an extract from the leaves of Lagerstroemia speciosa standardized to 1% corosolic acid (Glucosol) has been demonstrated in a randomized clinical trial involving Type II diabetics (non-insulin-dependent diabetes mellitus, NIDDM). Subjects received a daily oral dose of Glucosol and blood glucose levels were measured. Glucosol at daily dosages of 32 and 48mg for 2 weeks showed a significant reduction in the blood glucose levels. Glucosol in a soft gel capsule formulation showed a 30% decrease in blood glucose levels compared to a 20% drop seen with dry-powder filled hard gelatin capsule formulation (P<0.001), suggesting that the soft gel formulation has a better bioavailability than a dry-powder formulation.