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
After oral administration of [13C2] mevalonic acid at night, 20% +/- 0.7% of the dose was excreted in urine the following 12 hours, and only trace amounts thereafter. No [13C2] mevalonic acid could be detected in serum the following morning. We conclude that the absorption of dietary mevalonic acid and alcohol-induced mevalonic acid synthesis affects the urinary excretion and serum concentration of this cholesterol precursor.
Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis. In normolipemic volunteers, excretion of mevalonic acid averaged 3.51 +/- 0.59 (SD) ug/kg x day1; (n = 24) and was not different from patients with hypercholesterolemia (3.30 +/- 0.92 ug/kg x day1; n = 24). In patients with cerebrotendineous xanthomatosis, the excretion was significantly higher (8.55 +/- 1.92 ug/kg x day1; n = 6, P < 0.001) but comparable to volunteers treated with cholestyramine (6.69 +/- 2.6 ug/kg x day1; n = 5). A significant correlation was found between 24-hr excretion of mevalonic acid and cholesterol synthesis (r = 0.835; n = 35; P < 0.001). The coefficient of variation of excretion of mevalonic acid during 3 consecutive days was small (9.8%; n = 7). However, urinary output of mevalonic acid was significantly higher during the night (164 +/- 14 ug/12 hr) than during the day (129 +/- 9 ug/12 hr; n = 11; P < 0.05). In patients treated with simvastatin (40 mg/day) for 6 weeks, the ratio of mevalonic acid to creatinine in a morning urine sample decreased significantly compared to pretreatment values (110 +/- 25 ug/g vs. 66 +/- 25 ug/g; P < 0.001). Furthermore, the ratio of mevalonic acid to creatinine in a morning urine sample correlated with the ratio from the 24-hr collection period (r = 0.714; n = 34; P < 0.001). The results indicate that the analysis of urinary mevalonic acid, either in 24-hr collection or in a single morning sample, is an attractive method for evaluation of long and very short term changes of the rates of cholesterol synthesis.
... Plasma mevalonic acid (MVA) concentrations were correlated (i) with increased rates of whole-body cholesterol synthesis (measured by sterol-balance methods) in patients treated with cholestryamine resin (ii) with decreased rates of whole-body sterol synthesis (indicated by conversion of labeled acetate to sterol in freshly isolated mononuclear leukocytes) in out-patients after 4 weeks on a cholesterol-rich diet. In addition, a diurnal rhythm of plasma MVA concentrations was observed in patients whose activities were strictly controlled on a metabolic ward. At the peak of the rhythm (between midnight and 3 a.m.) MVA concentrations were 3-5 times greater than at the nadir (between 9 a.m. and noon). Furthermore, a relationship between the diurnal rhythm of plasma MVA and endogenous cholesterol synthesis is suggested by /the/ finding that the plasma MVA rhythm was suppressed by cholesterol feeding (1,200 mg/day) and abolished by a 12-day fast...

Interactions
... The effect of topical mevalonic acid on the murine epidermal permeability barrier function /was investigated/, comparing it with that of cholesterol. Topical treatment with acetone caused linear increases in transepidermal water loss, in proportion to the number of treatments more rapidly in aged mice than in young mice. Administration of mevalonic acid on aged murine epidermis enhanced its resistance against damage and the recovery rate of barrier function from acute barrier disruption. In contrast, although cholesterol also had the same effect, it required a much higher amount than mevalonic acid. In young mice, neither mevalonic acid nor cholesterol had any effect on resistance against acetone damage nor the recovery rate from acetone damage. In the skin of mice topically administered with mevalonic acid, stimulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity were both observed, whereas none was seen with stimulation by equimolar cholesterol. These data indicate that a topical application of mevalonic acid enhances barrier recovery in aged mice, which is accompanied by not only acceleration of cholesterol synthesis from mevalonic acid but also stimulation of the whole cholesterol biosynthesis.
The influence of 2 different alcoholic beverages containing an equal amount of alcohol (48 g), 1 with mevalonic acid (beer) and 1 without (vodka), on the urinary excretion and serum concentration of mevalonic acid was investigated in 7 healthy subjects. Drinking 1 L of beer at night containing 608 ug/L mevalonic acid more than doubled the urinary excretion of mevalonic acid the following 12 hours, on average from 103 +/- 15 microg/12 h to 211 +/- 17 ug/12 hr (P < .001; 18% of the administered dose). Drinking the same amount of alcohol as vodka had no effect, but urinary mevalonic acid output increased slightly the following day (7 AM to 7 PM) after ingestion of both alcoholic beverages. Serum concentrations of mevalonic acid were significantly increased the following morning after ingestion 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, P < .002 for both). An increase in the ratio of lathosterol to cholesterol in serum, another indicator of 3beta-hydroxy-3beta-methylglutaryl coenzyme A reductase activity in the liver, was also observed (+18% and +25%, respectively). ... Studies using mevalonic acid as a marker of cholesterol synthesis must be carefully monitored regarding dietary mevalonic acid intake and alcohol consumption.
Mevalonic acid is a product of the enzyme HMG-CoA reductase which is essential for cholesterol biosynthesis. Fluvastatin (Sandoz compound XU 62-320) is a potent inhibitor of this enzyme and, hence, mevalonic acid production. In three separate studies, oral administration of fluvastatin at 12 and 24 mg/kg/day to mated rats from day 15 of gestation through weaning resulted in unanticipated maternal mortality at the time of parturition and during lactation. Microscopic evaluations performed in two studies revealed significant cardiac myopathy in the dying animals. Drug-related clinical signs, significant maternal body weight loss, and an increase in stillborn pups and neonatal mortality were also noted at one or both dose levels. Supplementation of fluvastatin administration with 500 mg/kg b.i.d. of mevalonic acid completely blocked and/or ameliorated the mortality, cardiac myopathy, and other adverse effects. These studies indicate that the adverse maternal effects observed with fluvastatin before or following parturition resulted from exaggerated pharmacologic activity at the dose levels administered, i.e., inhibition of the enzyme HMG-CoA reductase, its immediate product mevalonic acid, and cholesterol biosynthesis.
... Mevalonic acid prevented the inhibitory effect of atorvastatin on cytokine-stimulated vascular cell adhesion molecule-1 expression and subsequent adhesion of THP-1 monocytes to the 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 racemate composed of equimolar amounts of (R)- and (S)-mevalonic acid. It has a role as a human urinary metabolite and a mouse metabolite. It contains a (R)-mevalonic acid and a (S)-mevalonic acid. It is a conjugate acid of a mevalonate.
Mevalonate has been reported in Drosophila melanogaster, Arabidopsis thaliana, and other organisms with data available.
A dihydroxy monocarboxylic acid and precursor in the biosynthetic pathway known as the mevalonate pathway, which produces terpenes and steroids that are vital for diverse cellular functions.

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Therapeutic Uses
/EXPL/ Twenty eight patients with heterozygous familial hypercholesterolemia were treated with mevalonic acid (an inhibitor of cholesterol synthesis) for 45 days. Patients received a daily dose of 750 to 1500 mg mevalonic acid depending on plasma cholesterol levels. Results showed a significant reduction in cholesterol values whereas no significant difference was observed in HDL cholesterol and triglyceride levels.

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.)