Tollovid: Brief Introduction

Tollovid® is a botanically – sourced dietary cleansing supplement sold directly to consumers in the United States and certain international markets. The recommended cleansing dose to support 3CL protease inhibition is 3 capsules 4 times daily until achieving desired results. The recommended cleansing dose to maintain desired 3CL protease levels is 1 capsule 2 times daily. One Tollovid® is delivered in capsule format and contains Lithospermum Erythrorhizon(sometimes called Gromwell) root extract and is qualified for 3CL protease (3CLpro, Main protease, Mpro, NSP5) inhibitory activity.


The main botanical ingredients of Tollovid® are derived from organic extracts of Lithospermum Erythrorhizon roots (Gromwell Extract), a plant species that is a member of the Lithospermeae tribe of the Boraginaceae plant family. Lithospermeae play important roles in Traditional Chinese Medicine and have a long history of safety and tolerability.  


NATURAL SOLUTION:Tollovid® is a botanically-sourced commercial product that is available as a supplement and sold directly to consumers in the US and certain European markets, and has a Certificate of Free Sale.   

Classification of Lithospermum and Arnebia (From NCBI: txid 34254 and 37312)



RECOMMENDED DOSE:

3 capsules, 4x daily

Main desired 3CL levels  

KEY TAKEAWAYS: 12 capsules/day contain up to approximately

<5mg of gromwell root

(Lithospermum Erythrorhizon) powder.

TOXICOLOGY, PK, ADME PUBLICATIONS

GR Extract Published Studies




STUDIES WITH GR EXTRACTS

Safety/Toxicology

1. In dogs, the no adverse effect level was 100 mg/kg/day of a hexane extract of Lithospermum containing acetyl shikonin, given for 28 days (Nam et al 2015).
2. In Sprague Dawley rats, no adverse effect level at more than 400 mg/kg/day of ethanol extract from Lithospermum given for 28 days (Han et al 2015).
3. In Fischer 344 rats, NOAEL of orally administered Lithospermum aqueous extract was higher than 2000 mg/kg/day over 13 weeks (Kim et al, 2019).
4. In Sprague Dawley rats, effects seen on fertility at 720 and 1080 mg/kg/day of ‘acetyl shikonin extract’ (DMSO?) from zicao (Lithospermum), but no such effects at 120 or 360 mg/kg/day. (He et al., 2016).
5. In Wistar rats, no tox at 800 mg/kg/day of an ethanol extract of Arnebia given for 6 months (Su et al, 2013).

Pharmacokinetics
PK data are available from studies in beagles indicate how Lithospermum extract accumulates with repeated dosing over the course of 28 days. 



ADME
Finally, Zhang et al (2020) reviewed studies concerning the distribution, absorption, and elimination of an index analyte of root. The results indicated: (In mice)... was mainly distributed in the stomach and intestine, secondarily in the gallbladder, liver, kidneys, lungs, and least in the brain and spinal cord. The cumulative excretion rate of feces and urine was nearly 80% within 48 h, mainly through fecal excretion. These results indicated that acetylshikonin had a wide distribution and poor absorption in mice. The binding rate of acetylshikonin to human plasma proteins was high. In general, acetylshikonin has a wide distribution, poor absorption, and high binding rate to human plasma proteins.

Disclosure: Aceytelshikonin is present at less than 1% in the proprietary Gromwell Root extraction process used to make Tollovid®.

Observations
• Studies use various root extracts .
• Extracts are not uniform, as some are hexane,some are ethanol, one is aqueous, one benzene, etc..
• Botanic sources can differ. Some are from Lithospermum,some are from Arnebia. 
• Note that our active compound is contained in root extract, but is not equal to acetykshikonin.
• No formal toxicology studies have yet been performed with Tollovid®.

PYRROLIZIDINE ALKALOID (PA) CONTENT

Tollo Health ensures the safety of its Tollovid® product lines by meeting or beating rigorous standards set by the European Union for pyrrolizidine alkaloid (PA) content of < 400 ug/kg. These alkaloids constitute a class of plant toxin associated with disease in humans and animals and are commonly found in certain plant species that are used as food supplements. The US FDA has not yet set required standards for PAs. Capsules from all commercial lots of Tollovid® have been tested by an external credentialed reference lab for the presence of PAs. All samples fell below the lower limit of detection for PA content (<5 ug/kg).  

Nam et al 2015 http://dx.doi.org/10.5487/TR.2015.31.1.077
Han et al 2015 http://dx.doi.org/10.5487/TR.2015.31.4.403
Kim et al 2019 
https://doi.org/10.1016/j.jep.2019.01.034
Su et al 2013 https://doi.org/10.3109/13880209.2013.846913
Zhang et al 2020 https://doi.org/10.1080/13880209.2020.1818793

HEAVY METALS
Tollo Health ensures compliance with the most rigorous US standards for food supplements in the United States. All batches of Tollovid® are tested for heavy metal toxins and pass current Good Manufacturing Practices (cGMP) quality controls. The titanium dioxide contained in the gelcap surrounding the Tollovid® ingredients is known to be non-carcinogenic when ingested orally. Material from all commercial lots of Tollovid® have been tested by credentialed third-party reference laboratories selected by our contract manufacturer to test for heavy metal.

CONTRACT MANUFACTURER 

Tollovid® is manufactured at American Health Formulations (AHF - www.ahfvitamins.com), a cGMP manufacturer of dietary supplement and Medical Food products in Hauppauge, New York. AHF is a member of the American Botanical Manufacturing Association. Tollovid® is Made in the USA.

SIDE EFFECTS 

The only known common side effect of Tollovid® is that it causes stool to turn dark. This is because some of the ingredients are also used as natural dyes in food, specifically for dark purple. This is not associated with any other side effects.

How Tollovid™ Uses 3CL Protease Inhibitors to Fight Infections