Mevalonate (80, 90, 100, 110 µM; 72 hours) inhibits simvastatin-induced loss of C2C12 myotube cell viability in vitro [1].

Cell viability assay [1]
Cell Types: C2C12 cells (simvastatin induced)
Tested Concentrations: 80, 90, 100, 110 µM
Incubation Duration: 72 hrs (hours)
Experimental Results: demonstrated no decrease in cell viability.

Absorption, Distribution and Excretion
Following oral administration of [13C2]mevalerate at bedtime, 20% ± 0.7% of the dose was excreted in the urine within 12 hours, with only trace amounts excreted thereafter. [13C2]mevalerate was not detected in serum the following morning. We conclude that dietary mevalerate absorption and alcohol-induced mevalerate synthesis affect the urinary excretion and serum concentration of this cholesterol precursor. We investigated urinary excretion of mevalerate as an indicator of cholesterol synthesis. In volunteers with normal lipid levels, the mean excretion of mevalerate was 3.51 ± 0.59 (SD) μg/kg·d⁻¹ (n=24), which was not significantly different from that in patients with hypercholesterolemia (3.30 ± 0.92 μg/kg·d⁻¹; n=24). In patients with cerebral tendinitis xanthomas, mevalonic acid excretion was significantly elevated (8.55 ± 1.92 μg/kg·d⁻¹; n = 6, P < 0.001), but comparable to that in volunteers receiving cholestyramine (6.69 ± 2.6 μg/kg·d⁻¹; n = 5). A significant correlation was found between 24-hour mevalonic acid excretion and cholesterol synthesis (r = 0.835; n = 35; P < 0.001). The coefficient of variation for 3-day mevalonic acid excretion was small (9.8%; n = 7). However, nocturnal urinary mevalonic acid excretion (164 ± 14 μg/12 hours) was significantly higher than daytime excretion (129 ± 9 μg/12 hours; n = 11; P < 0.05). In patients treated with simvastatin (40 mg/day) for 6 weeks, the ratio of mevalonate to creatinine in morning urine was significantly lower than before treatment (110 ± 25 μg/g vs. 66 ± 25 μg/g; P < 0.001). Furthermore, the ratio of mevalonate to creatinine in morning urine was positively correlated with the ratio collected during 24-hour urine collection (r = 0.714; n = 34; P < 0.001). These results indicate that urinary mevalonate analysis, whether using 24-hour urine collection or a single morning urine sample, is an effective method for assessing long-term and short-term changes in cholesterol synthesis rates. Plasma mevalonate (MVA) concentrations were associated with: (i) elevated systemic cholesterol synthesis rates (measured by the sterol balance method) in patients receiving cholestyramine resin therapy; and (ii) decreased systemic sterol synthesis rates (measured by the conversion rate of labeled acetate to sterols in freshly isolated mononuclear leukocytes) in outpatients on a high-cholesterol diet for 4 weeks. Furthermore, a diurnal rhythm of plasma MVA concentrations was observed in patients under strict activity control in the metabolic ward. During peak periods (between midnight and 3 a.m.), MVA concentrations were 3–5 times higher than during trough periods (between 9 a.m. and 12 p.m.). Additionally, studies found an association between the diurnal rhythm of plasma MVA and endogenous cholesterol synthesis, as cholesterol feeding (1200 mg/day) suppressed the diurnal rhythm of plasma MVA, while 12 days of fasting eliminated this rhythm…

Interactions
This study investigated the effects of topical mevalonic acid (MAA) on the permeability barrier function of the epidermis in mice and compared it with cholesterol. Topical application of acetone led to a linear increase in transepidermal water loss, with the increase occurring more rapidly in older mice than in younger mice, and was proportional to the number of treatments. MAA application to the epidermis of older mice enhanced their resistance to damage and accelerated the recovery of barrier function from acute disruption. In contrast, while cholesterol had the same effect, the required dose was much higher than that of MAA. In younger mice, neither MAA nor cholesterol had any effect on resistance to acetone damage or the rate of recovery from acetone damage. In mouse skin treated with topical MAA, stimulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl-CoA reductase activity was observed, while no such stimulation was observed with equimolar cholesterol. These data suggest that topical application of MAA enhances the recovery of barrier function in older mice, not only through accelerated cholesterol synthesis but also through stimulation of the entire cholesterol biosynthesis process. This study investigated the effects of two alcoholic beverages with the same alcohol content (48 grams) (one containing mevalonic acid, i.e., beer; the other without mevalonic acid, i.e., vodka) on urinary mevalonic acid excretion and serum mevalonic acid concentration in seven healthy subjects. Results showed that after subjects consumed 1 liter of beer containing 608 μg/L mevalonic acid before bedtime, urinary mevalonic acid excretion more than doubled within 12 hours, increasing from an average of 103 ± 15 μg/12 hours to 211 ± 17 μg/12 hours (P < 0.001; equivalent to 18% of the administered dose). Consuming equal amounts of alcoholic beverages (beer and vodka) had no effect on urinary mevalonic acid excretion, but urinary mevalonic acid excretion slightly increased the following day (7:00 AM to 7:00 PM) after consuming either beverage. Following consumption of beer (from 3.22 ± 0.20 ng/mL to 6.79 ± 0.58 ng/mL) or vodka (from 3.23 ± 0.37 ng/mL to 5.36 ± 0.55 ng/mL, both P values < 0.002), serum mevalonic acid concentrations significantly increased the following morning. Furthermore, the serum lanosterol-to-cholesterol ratio also increased (by 18% and 25%, respectively), which is another indicator of the activity of 3β-hydroxy-3β-methylglutaryl-CoA reductase in the liver. …Studies using mevalonic acid as a marker of cholesterol synthesis must closely monitor dietary mevalonic acid intake and alcohol consumption. Mevalonic acid is a product of HMG-CoA reductase, an enzyme essential for cholesterol biosynthesis. Fluvastatin (Sandoz compound XU 62-320) is a potent inhibitor of this enzyme, thus inhibiting the production of mevalonic acid. In three independent studies, oral administration of fluvastatin at doses of 12 and 24 mg/kg daily from day 15 of gestation to weaning resulted in unexpected maternal deaths during parturition and lactation in mated rats. Microscopic examination in two of the studies revealed significant cardiomyopathy in the deceased animals. At one or both dose levels, drug-related clinical symptoms, significant maternal weight loss, and increased stillbirth and neonatal mortality were also observed. Supplementation with 500 mg/kg mevalonic acid twice daily on top of fluvastatin treatment completely blocked and/or reduced mortality, cardiomyopathy, and other adverse reactions. These studies suggest that the adverse maternal reactions observed with prenatal or postnatal fluvastatin administration are due to excessive drug activity at the administered dose levels, specifically inhibition of HMG-CoA reductase and its direct product mevalonic acid synthesis, as well as cholesterol biosynthesis. ...Mevalerate can prevent atorvastatin from inhibiting the expression of cytokine-stimulated vascular cell adhesion molecule-1 and inhibit the subsequent adhesion of THP-1 monocytes to cultured endothelial cells.

[1]. Coenzyme Q nanodisks counteract the effect of statins on C2C12 myotubes. Nanomedicine. 2021 Oct;37:102439.

[2]. Cholesterol and mevalonic acid modulation in cell metabolism and multiplication. Toxicol Lett. 1992 Dec;64-65 Spec No:1-15.

Mevalonic acid is a racemic mixture composed of equimolar amounts of (R)- and (S)-methvalonic acid. It is a metabolite found in both human urine and mice. It contains one (R)-methvalonic acid and one (S)-methvalonic acid. It is the conjugate acid of mevalonic acid. Mevalonic acid has been reported in Drosophila, Arabidopsis, and other organisms with relevant data. Mevalonic acid is a dihydroxy monocarboxylic acid and a precursor in the mevalonic acid pathway biosynthesis, which generates terpenoids and steroids essential for various cellular functions.
Therapeutic Use
/EXPL/ 28 patients with heterozygous familial hypercholesterolemia received 45 days of treatment with mevalonic acid (a cholesterol synthesis inhibitor). Patients received 750 to 1500 mg of mevalonic acid daily, depending on their plasma cholesterol levels. Results showed a significant reduction in cholesterol levels, while high-density lipoprotein cholesterol and triglyceride levels did not change significantly.

C6H12O4

148.15708

148.074

150-97-0

Mevalonic acid lithium salt;2618458-93-6

449

White to off-white solid powder

1.263g/cm3

364.128°C at 760 mmHg

188.204°C

8.91E-07mmHg at 25°C

-1

3

4

4

10

123

0

KJTLQQUUPVSXIM-UHFFFAOYSA-N

InChI=1S/C6H12O4/c1-6(10,2-3-7)4-5(8)9/h7,10H,2-4H2,1H3,(H,8,9)

3,5-dihydroxy-3-methylpentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)