The research

The complete formula,
studied and published.

The whole six-ingredient formula — not one isolated raw material — was given to mice in a model of cardiovascular-kidney-metabolic syndrome and the results were published, peer-reviewed and open access, in Nutrients. This page reports what the study did and what it found, including what it did not show.

Preclinical · animal modelPeer-reviewedn = 35 mice 12 weeksOpen access · CC BY 4.0

What was tested

The formula in the study is the formula in the pouch.

Supplement studies usually test one raw material and the finished product then borrows the credit. Here the composition given to the animals matches the label milligram for milligram, per capsule.

Ingredient	In the study	On the pouch
L-arginine	175 mg	175 mg
L-citrulline	125 mg	125 mg
Beetroot	100 mg	100 mg
Rhodiola rosea	100 mg	100 mg
Magnesium	25 mg	25 mg
Vitamin C	25 mg	25 mg

Per capsule. The study administered the formula dissolved in drinking water rather than as capsules.

01 · Study design

Three groups, twelve weeks.

Male C57BL/6J mice. One kidney removed by surgery, then a Western diet high in salt, sugar and fat — the standard way to induce this syndrome in an animal.

Control

Sham surgery, standard chow

Disease model

Nephrectomy + Western diet

Disease model + FLX

Same, plus Flexovital in the drinking water

Step 01
Acclimatisation
One week before anything begins.
Step 02
Surgery
Unilateral nephrectomy, or sham surgery for the control group.
Step 03
Seven days later
Randomisation, and the intervention starts.
Step 04
Twelve weeks later
Measurements in vivo and ex vivo, then histology and biochemistry.

02 · The preparation

What was given.

Flexovital, dissolved in the drinking water at 25 g per litre, for the whole twelve weeks.

Mechanism, as the article states it

L-arginine and L-citrulline act as substrates for the body’s own nitric oxide production. Beetroot extract contributes dietary nitrate, which is a separate route to the same molecule. The role of Rhodiola rosea is not fully understood.

Because the formulation was given as a whole, the contribution of any single ingredient cannot be separated out.

03 · Results

What the study reports.

Every figure below is measured against the untreated disease group, not against the healthy control.

Tubular injury in kidney tissue

Score 1–10. Tissue samples were graded by a histopathologist who did not know which group they came from.

↓ Lower bar = less tissue damage

1,0 ControlSham surgery
standard chow 6,6 Disease modelNephrectomy
Western diet 4,5 + FlexovitalSame model
with FLX

−32% lower injury score with Flexovital than in the untreated disease modelp < 0.05

Values from the paper’s discussion: 1.0 in the control group, 6.6 in the disease model and 4.5 with Flexovital.

Body composition

Body composition worsened in the disease model. According to the paper that decline was largely absent in the group given Flexovital.

↓ Shorter bar = closer to normal

Fat-to-lean ratio Disease model +20% With Flexovital near normal

The ratio rose about 20% in the disease model. With Flexovital it was close to normalised. p < 0.01

Adipocyte area Disease model +30% With Flexovital near normal

Adipocyte area rose more than 30% in the disease model. With Flexovital it was close to normalised. p < 0.001

Weight gain Disease model reference With Flexovital −22%

Weight gain was 22% lower with Flexovital than in the untreated disease model. p < 0.05

IL-6, a marker of inflammation, measured 0.03 ± 0.05 with Flexovital against 0.14 ± 0.26 in the disease model. The difference was not statistically significant.

Other outcomes

Organ system by organ system.

The following parameters appear in the paper only as figures, with no numbers in the running text. They are given here in the authors’ own terms.

Statistically significant Trend, not significant No difference

Heart and vessels

5 parameters

Mean arterial pressure The average pressure in the arteries across a whole heartbeat. Significantly reduced Fig. 5A

Systolic and diastolic pressure The upper and lower blood pressure readings — the pressure while the heart pumps, and while it rests between beats. Significantly reduced Fig. 5B–C

Endothelium-dependent vasodilation The ability of a vessel to widen. It is governed by the endothelium, the thin cell layer lining the vessel that releases nitric oxide. Clearly improved Fig. 6C

Troponin I A protein inside heart muscle cells. When the cells are damaged it leaks into the blood, and clinics use the level as a measure of heart muscle injury. In the disease model it was two to three times elevated. Trend towards a lower level, close to the control group (p = 0.10) Fig. 5E

Heart rate Beats per minute. No difference between groups Fig. 5D

Kidney

4 parameters

Glomerular filtration rate Abbreviated GFR. It measures how much blood the kidneys clean per minute, and is the most common measure of kidney function. Significantly improved (p < 0.05) Fig. 7B

Glomerular injury Damage to the glomeruli, the kidney’s microscopic filter units. One kidney holds around a million of them. Reduced (p < 0.001) Fig. 7D

Mitochondrial P/O ratio A measure of how efficiently mitochondria — the cell’s power plants — convert oxygen into usable energy. Increased oxygen efficiency Fig. 7A

Albuminuria The protein albumin in the urine. Healthy kidneys do not let it through, so its presence is an early sign of kidney involvement. Clear trend towards a reduction Fig. 7F

Metabolism

2 parameters

Fasting glucose Blood sugar measured after five hours without food. Raised values are an early sign of disturbed sugar metabolism. Reduced Fig. 4C

Insulin response How well the body lowers blood sugar when insulin is given. A weak response points to insulin resistance. Improved Fig. 4D

Measured, but not significant

Interleukin-6 was 0.03 ± 0.05 in the treated group against 0.14 ± 0.26 in the untreated model — a difference in the expected direction that did not reach statistical significance. Serum troponin I rose two- to threefold in the disease model; the treated group came out at p = 0.10. Both are honest nulls, not findings.

What the study does not show.

This is a preclinical study in mice, not a clinical trial in people. It says nothing about what the formula does in a healthy person, and it is not evidence that any disease can be prevented, treated or cured. The animals received the formula in drinking water at a dose set for the model, not the human daily dose. Eight animals received the intervention. The authors themselves conclude that the results need validation in human trials.

04 · Source

The publication.

Title: Protective Effects of the Food Supplement Flexovital in a Model of Cardiovascular-Kidney-Metabolic Syndrome in Mice
Authors: Carvalho LRRA, Tydén M, Shimari M, Zhuge Z, Schiffer TA, de Oliveira Monteiro MM, Lundberg JO, Weitzberg E, Andersson DC, Fellström B, Carlström M
Karolinska Institutet, Uppsala University and Karolinska University Hospital.
Journal: Nutrients 16(23):4105
Published: 28 November 2024
Review: Peer-reviewed
Licence: CC BY 4.0
DOI: 10.3390/nu16234105

Read the full paper

Disclosure

The study was carried out at Swedish universities. Bengt Fellström, who developed Flexovital, is a co-author and has a financial interest in BioConcept AB. That interest is declared in the paper’s conflict-of-interest statement, and it is declared here.

Timeline

Where this comes from, and where it goes.

1998
Nobel Prize in Medicine
Awarded for the discovery of nitric oxide as a signalling molecule in the cardiovascular system.
2003
BioConcept founded
In Uppsala. The formula is built around that molecule rather than around a single raw material.
Nov 2024
Published in Nutrients
The complete formula, peer-reviewed and open access.
Next
Longevity study
To be presented shortly.
After that
Human clinical trial
Planned. Until it reports, everything on this page is preclinical.

Six ingredients. Every dose printed.

The formula that was studied is the one in the pouch.

See the product Ingredient by ingredient

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Flexovital N.O.RDIC is a food supplement. Food supplements do not replace a varied diet and a healthy lifestyle. Do not exceed the recommended daily dose.

The complete formula,studied and published.