The Plasma Bioavailability of Coenzyme Q10 Absorbed from the Gut and the Oral Mucosa

Coenzyme Q10 (CoQ10) has a central role in the generation of cellular bioenergy and its regulation. The hydrophobicity exhibited by the CoQ10 molecule leads to reports of poor absorption profiles, therefore, the optimization of formulations and modes of delivery is an ever-evolving therapeutic goal. The aim of this study was to investigate different CoQ10 formulations. The article summarizes the findings from an Australian comparative study involving adults administered CoQ10 through different oral delivery platforms. A total of 11 participants (six males and five females) voluntarily participated in a comparative clinical study of three different CoQ10 formulations across a six-week period, completing 198 person-hours of cumulative contribution equivalent to n = 33 participation. All of the eligible participants (n = 11) administered the three formulations blinded from who the commercial supplier of the formulation was and from what the chemical form of the CoQ10 was that was being administered. The dosing between the CoQ10 preparations were dispensed sequentially and were administered following three-week washouts. Three commercial preparations were tested, which included the following: formulations with capsules each containing ubiquinol and ubiquinone (150 mg/capsule), and a liposome ubiquinone formulation (40 mg/mL at 2 actuations of the pump). A significant inter-subject variation in the plasma level of CoQ10 at baseline that was observed to increase with an increase in age. This trend persisted in the post administration of the different formulations. Furthermore, it was observed that the intestinal absorption and bioavailability of CoQ10 varied significantly in the plasma between subjects, irrespective of whether the ubiquinol or ubiquinone forms were administered. The administration of CoQ10 as a liposome for preparation showed the poorest response in bioavailability. Although the ubiquinol capsule form of CoQ10 was observed to have increased in the plasma versus the ubiquinone capsules and the ubiquinol liposome at the two-hour interval, the inter-subject variation was such that the difference was not significant (p > 0.05). All of the CoQ10 formulations showed no further increases in their plasma levels over the remaining study period (i.e., four hours). This study further concluded that the intestinal absorption of CoQ10 is highly variable and is independent of the molecular form administered. Furthermore, it also concludes that liposomes are not an effective vehicle for the oral administration of CoQ10, and as such, did not improve the oral mucosal/sublingual absorption and bioavailability of the molecule. Of interest was the observation that with the increasing subject age, there was an observed increase in the baseline plasma CoQ10 levels in the participants prior to dosing. It was posited that the increase in the baseline plasma levels of CoQ10 with an increase in age could be due to the loss of skeletal muscle mass, a result that still needs to be verified.

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Platelet Aggregation, β-Thromboglobulin and Platelet Factor 4 in Diabetes Mellitus and in Patients with Vasculopathy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661186 ◽

1984 ◽

Vol 52 (03) ◽

pp. 236-239 ◽

Cited By ~ 24

Author(s):

J Fritschi ◽

M Christe ◽

B Lämmle ◽

G A Marbet ◽

W Berger ◽

...

Keyword(s):

Diabetes Mellitus ◽

Platelet Aggregation ◽

Discriminant Analysis ◽

Plasma Levels ◽

Platelet Activating Factor ◽

Platelet Factor 4 ◽

Platelet Factor ◽

Aggregation Response ◽

The Difference

SummaryWe have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. β-Thromboglobulin (β-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of β-TG and the stages of either retinopathy or macroangiopathy or nephropathy. The difference is more marked between normals and diabetics with neuropathy (p = 0.026). The aggregation response to ADP and platelet activating factor (PAF) is enhanced at lower stimulator concentration. Using the β-TG, PF4 and aggregation values the discriminant analysis allows a distinction of several subgroups especially with nephropathy and neuropathy (Table 6).

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Strategies for Oral Delivery of Metal-Saturated Lactoferrin

Current Protein and Peptide Science ◽

10.2174/1389203720666190513085839 ◽

2019 ◽

Vol 20 (11) ◽

pp. 1046-1051 ◽

Cited By ~ 1

Author(s):

Przemysław Gajda-Morszewski ◽

Klaudyna Śpiewak-Wojtyła ◽

Maria Oszajca ◽

Małgorzata Brindell

Keyword(s):

Biological Activity ◽

Oral Delivery ◽

Therapeutic Potential ◽

Structure And Function ◽

The Difference ◽

And Function ◽

First Time

Lactoferrin was isolated and purified for the first time over 50-years ago. Since then, extensive studies on the structure and function of this protein have been performed and the research is still being continued. In this mini-review we focus on presenting recent scientific efforts towards the elucidation of the role and therapeutic potential of lactoferrin saturated with iron(III) or manganese(III) ions. The difference in biological activity of metal-saturated lactoferrin vs. the unmetalated one is emphasized. The strategies for oral delivery of lactoferrin, are also reviewed, with particular attention to the metalated protein.

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Plasma Levels and Intestinal Absorption of 25-Hydroxyvitamin D after small Intestinal Resection

Vitamin D - Biochemical, Chemical and Clinical Aspects Related to Calcium Metabolism ◽

10.1515/9783112327203-134 ◽

1977 ◽

pp. 763-766

Keyword(s):

Intestinal Absorption ◽

Plasma Levels ◽

Intestinal Resection ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Small Intestinal

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Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes

Scientific Reports ◽

10.1038/s41598-021-88970-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hongseok Yoo ◽

Yunjoo Im ◽

Ryoung-Eun Ko ◽

Jin Young Lee ◽

Junseon Park ◽

...

Keyword(s):

Plasma Levels ◽

Validation Cohort ◽

High Mobility ◽

Kinase Domain ◽

High Mobility Group ◽

Rank Test ◽

Enzyme Linked Immunosorbent Assay ◽

Derivation Cohort ◽

The Difference

AbstractThe role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.

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Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽

10.3390/nu11092147 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2147 ◽

Cited By ~ 42

Author(s):

Michele Dei Cas ◽

Riccardo Ghidoni

Keyword(s):

Small Intestine ◽

Cellular Uptake ◽

Oral Delivery ◽

Therapeutic Potential ◽

Pharmacokinetic Profile ◽

Yellow Pigment ◽

The Body ◽

Anti Cancer ◽

Poor Absorption ◽

Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

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Effects of acute and chronic treatment with glucocorticoids on the intestinal absorption of calcium and phosphate and on plasma 1,25-dihydroxyvitamin D levels in pigs

Clinical Science ◽

10.1042/cs0690553 ◽

1985 ◽

Vol 69 (5) ◽

pp. 553-559 ◽

Cited By ~ 8

Author(s):

John Fox ◽

Richardus Ross ◽

Anthony D. Care

Keyword(s):

Intestinal Absorption ◽

Plasma Levels ◽

Time Course ◽

Chronic Treatment ◽

Intestinal Loop ◽

Phosphate Absorption ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Young Pigs ◽

Proximal Small Intestine

1. We have used young pigs, each prepared surgically with a Thiry-Vella loop of proximal small intestine, to study the time course of changes in the intestinal absorption of calcium, phosphate, sodium, glucose and water and on the plasma levels of 1,25-dihydroxyvitamin D after treatment of the animals with glucocorticoids. 2. Perfusion of the intestinal loop for 6 h with a solution containing hydrocortisone or betamethasone was without effect on the absorption of calcium or phosphate. 3. The oral administration of betamethasone stimulated the absorption of calcium and phosphate by 15–20% for 2–3 days before the trend was reversed and absorption was progressively reduced. 4. Chronic treatment with betamethasone inhibited only the active component of calcium and phosphate absorption. 5. Treatment with betamethasone was associated with a sustained 25–50% increase, to a maximum by 2 days, in the absorption of sodium, glucose and water. 6. Plasma levels of 1,25-dihydroxyvitamin D were reduced within 2 days of the start of treatment and reached a minimum (40–50% decrease) in 4–6 days. 7. We conclude that the initial stimulation of calcium and phosphate absorption is caused by the increased absorption of water. The long-term decrease in absorption may not be caused solely by the decreased circulating levels of 1,25-dihydroxyvitamin D since absorption continued to fall for several weeks after 1,25-dihydroxyvitamin D levels had reached a minimum.

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THE ACCUMULATION OF ELECTROLYTES

The Journal of General Physiology ◽

10.1085/jgp.15.6.667 ◽

1932 ◽

Vol 15 (6) ◽

pp. 667-689 ◽

Cited By ~ 40

Author(s):

W. J. V. Osterhout ◽

W. M. Stanley

Keyword(s):

Steady State ◽

Osmotic Pressure ◽

Aqueous Phase ◽

Thermodynamic Potential ◽

Ph Value ◽

Molecular Form ◽

External Solution ◽

Aqueous Layer ◽

The Difference ◽

Pass Through

Inasmuch as attempts to explain accumulation by the Donnan principle have failed in the case of Valonia, a hypothesis of the steady state has been formulated to explain what occurs. In order to see whether this hypothesis is in harmony with physico-chemical laws attempts have been made to imitate its chief features by means of a model. The model consists of a non-aqueous layer (representing the protoplasmic surface) placed between an alkaline aqueous phase (representing the external solution) and a more acid aqueous phase (representing the cell sap). The model reproduces most of the features of the hypothesis. Attention may be called to the following points. 1. The semipermeable surface is a continuous non-aqueous phase. 2. Potassium penetrates by combining with an acid HX in the non-aqueous layer to form KX which in turn reacts with an acid HA in the sap to form KA. Since KX is little dissociated in the non-aqueous layer potassium appears to pass through it chiefly in molecular form. 3. The internal composition depends on permeability, e.g., sodium penetrates less rapidly than potassium and in consequence potassium predominates over sodium in the "artificial sap." The order of penetration in the model is the same as in Valonia, i.e., K > Na > Ca > Mg, and Cl > SO4, but the quantitative resemblance is not close, e.g., the difference between potassium and sodium, and chloride and sulfate is much less in the model. 4. The formation of KA and NaA in the sap raises its osmotic pressure and water enters. 5. The concentration of potassium and sodium and the osmotic pressure become much greater inside than outside. For example, potassium may become 200 times as concentrated inside as outside. 6. No equilibrium occurs but a steady state is reached in which water and salt enter at the same rate so that the composition of the sap remains constant as its volume increases. 7. Since no equilibrium occurs there is a difference of thermodynamic potential between inside and outside. At the start the thermodynamic potential of KOH is much greater outside than inside. This difference gradually diminishes and in the steady state has about the same value as in Valonia. The difference in pH value between the internal and external solutions is also similar in both cases (about 2 pH units). 8. Accumulation does not depend on the presence of molecules or ions inside which are unable to pass out. One important feature of the hypothesis is not seen in the model: this is the exchange of HCO3 for Cl-. Experiments on this point are in progress.

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EFFECTS OF CONTINUOUS DAILY ADMINISTRATION OF 0.5 mg OF CHLORMADINONE ACETATE ON THE PLASMA LEVELS OF PROGESTERONE AND ON THE URINARY EXCRETION OF LUTEINIZING HORMONE AND TOTAL OESTROGENS

Acta Endocrinologica ◽

10.1530/acta.0.0630705 ◽

1970 ◽

Vol 63 (4) ◽

pp. 705-716 ◽

Cited By ~ 12

Author(s):

U. Larsson-Cohn ◽

E. D. B. Johansson ◽

L. Wide ◽

C. Gemzell

Keyword(s):

Luteinizing Hormone ◽

Plasma Level ◽

Urinary Excretion ◽

Corpus Luteum ◽

Plasma Levels ◽

Chlormadinone Acetate ◽

The Mean ◽

Low Levels ◽

The Difference ◽

All Treatment

ABSTRACT Daily determinations of the plasma level of progesterone and the urinary excretion of luteinizing hormone (LH) and total oestrogens were performed in 6 subjects during one control cycle, immediately followed by three cycles of daily treatment with 0.5 mg of chlormadinone acetate continuously. The control cycles were ovulatory according to the parameters investigated. Two of the women showed a normal LH excretion pattern in all treatment cycles. The four other subjects also had periodical variations in the LH excretion but no distinct midcycle peaks occurred. The mean oestrogen excretion was increased in all three treatment cycles but the difference was satistically significant only in the last two cycles. Compared with the treatment cycles, the sum of progesterone values was significantly decreased in the first two cycles. Chlormadinone acetate in this dose had no thermogenic effect. Three of the subjects showed bleeding irregularities which had no clear connection with the hormone variations measured in the study. It is suggested that the low levels of progesterone might be due to a defective corpus luteum function.

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Studies of Blood Lipid Fractions of Quiescent Rheumatic Fever Patients and Their Siblings

Clinical Chemistry ◽

10.1093/clinchem/5.6.557 ◽

1959 ◽

Vol 5 (6) ◽

pp. 557-565 ◽

Cited By ~ 2

Author(s):

Harold D Appleton ◽

Alvin F Coburn ◽

Yale L Meltzer

Keyword(s):

Rheumatic Fever ◽

Normal Level ◽

Plasma Levels ◽

Blood Lipids ◽

Lipid Fraction ◽

Blood Lipid ◽

Low Level ◽

Lipid Fractions ◽

The Difference

Abstract Three phospholipid fractions have been determined in plasmas of quiescent rheumatic children and their siblings of similar ages. The method for determining blood lecithin gave reproducible results, and the lipid fraction appeared indicative of difference in levels of blood lipids between rheumatic and nonrheumatic children. In this series of lecithin determinations only one rheumatic subject had a high normal level and only one sibling (presumably nonrheumatic) had a low level. The difference in mean nonfasting lecithin plasma levels between rheumatic subjects and siblings was 0.36 mMol./L. Similarly, the lecithin level of each of the nonrheumatic siblings in this series averaged 0.41 mMol./L. higher than that of the corresponding quiescent rheumatic child. In both of these differences P <0.05.

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