Frequently Asked Questions

Manufacturing Standards          

 

How does PreCardix® maintain consistency in the active ingredient in the manufacturing process?

Each 1,200 mg dose (2 tablets) of PreCardix® consists of approximately 25,000 unique bioactive peptides that exert ACE-inhibiting properties. Each batch of PreCardix® must meet Marealis AS strict internal standards before it is released for commercial use to ensure the product will always meet the promised blood pressure-lowering attributes. This consistency and efficacy are ensured by testing the product for bioactivity and ACE-inhibiting attributes before and after the product is manufactured in tablet form.

 

What are the ingredients in PreCardix®?            

Each tablet contains 600 mg of protein hydrolysate from cold water shrimp (Pandalus borealis) shell. The active medicinal ingredient is Refined Shrimp Peptide Concentrate (RSPC) made up of peptides 2-7 amino acids long which pass unmodified into the bloodstream. These bioactive peptides work synergistically to produce ACE-inhibiting effects.

Some peptides exert direct ACE-inhibition and two of the most potent constituents in PreCardix® have been patented. The non-medicinal ingredients required for tablet manufacturing and palatability are; microcystalline cellulose, croscarmelose sodium, magnesium stearate, silicon dioxide, polyethelene glycol, talc (<20mg of USP-NF talc in the tablet’s coating), polyvinyl alcohol, titanium dioxide. “

 

Is PreCardix® derived from just shrimp? Or shrimp and shellfish?           

PreCardix® is derived from the shells of cold-water Arctic prawns (Pandalus Borealis). No other shellfish or species are used to produce PreCardix®.

 

Can the dose (1,200 mg) be quantified in the number of shrimp shells?         

The shells of 1 kg of shrimp, when extracted and refined through our proprietary controlled enzymatic hydrolysis process, provide active ingredient equaling approximately a 1-month dosage of PreCardix®.

The shrimp proteins are refined through a proprietary enzymatic hydrolysis process to produce the ACE-inhibiting attributes associated with the peptides in the final product. Shells contain in-tact proteins and would not have the same blood pressure-lowering effect.

 

What is a ‘Certified B Corporation’?      

Certified B Corporations (B Corps) are businesses that meet the highest standard of social and environmental performance, public transparency, and legal accountability to balance profit and purpose. B Corps are crucial in facilitating and accelerating a global culture shift to redefine success in business and build a more inclusive and sustainable economy.

 

Is PreCardix® only available in Canada?

PreCardix® is currently only available in Canada. Distribution in the U.S., Ghana, and the U.K. is in progress.

 

Dosing and Administration        

 

How should I prescribe PreCardix® to my patients?                                                      

The recommended dose of PreCardix® is 2 tablets (1,200 mg of the active ingredient) a day. Ideally, the tablets should be taken together before noon and away from other medications, natural health products and food.

Patients should take PreCardix® for a minimum of 8 weeks before determining if the treatment is effective. This timeline is based on clinical research, in which 89% of participants saw a significant reduction in blood pressure after 8 weeks compared to baseline.

PreCardix® should be taken on an ongoing basis to maintain its blood pressure lowering effects if discontinued prematurely blood pressure can rise to pre-treatment levels.

 

How soon can patients expect to see a reduction in blood pressure after starting PreCardix®?

Patients should take PreCardix® for a minimum of 8 weeks before determining the efficacy of treatment. In clinical trials, 31% of patients had a significant reduction in their blood pressure after just 2 weeks and by week 8, 89% of participants had a significant reduction in their blood pressure from baseline.

PreCardix® should be taken daily on an ongoing basis. Blood pressure may rise to pre-treatment levels with the cessation of treatment.

 

How long would you recommend using PreCardix® before moving to conventional medications to manage blood pressure?  

Take PreCardix® daily as directed for a minimum of 8 weeks before determining clinical efficacy. In the clinical trial, 89% of participants experienced a statistically significant reduction in blood pressure compared to baseline after eight weeks.

 

Other than blood pressure, are there any recommended monitoring parameters for patients who choose PreCardix®?                                                                                                                                                

PreCardix® did not impact serum potassium or kidney function in clinical research. Considering PreCardix®  is a natural ACE-I, monitoring these parameters along with blood sugars at baseline and throughout treatment may be warranted at the practitioner’s discretion.

 

What is the dosage as an adjunct as compared to preventative or pre-diagnosed blood pressure treatment?  

PreCardix® has not been studied in clinical research as an adjunct to antihypertensive medication. PreCardix® has been studied in a healthy adult population without co-morbidities or other medications and in the dose of 1,200mg a day only.

In market reports from customers who have added PreCardix® alongside antihypertensive medication under the direction and guidance of their physician have used two tablets of PreCardix® daily, the same dose found to be effective in clinical research in unmedicated patients with mild-moderate elevated blood pressure at baseline.

 

Does PreCardix® need to be kept in the refridgerator?

No, PreCardix® does not need to be refrigerated, it should be stored at room temperature.

 

Co-administration with Medications     

 

Can you combine PreCardix®  with anti-hypertensive medication?         

PreCardix® has not been directly studied in clinical trials in combination with anti-hypertensive medications. However, in-market research suggests that adding PreCardix® to an existing pharmaceutical protocol under healthcare practitioner supervision promotes further reduction in blood pressure.

There have been no reports of drug interactions or hypotension based on this in-market research. Patients who are on both PreCardix® and anti-hypertensive medications should be monitored by the prescribing physician for adverse effects including hypotension.

 

Could PreCardix® be used an adjunct treatment for patients not achieving blood control using ACE-inhibitors, or is it better to use as an adjunct with other antihypertensive classes?

In the clinical trial, PreCardix® was not studied in combination with any classes of antihypertensive medications. In-market research suggests that adding PreCardix® to an existing pharmaceutical protocol under healthcare practitioner supervision could further reduce blood pressure.

No large-scale trials to confirm the efficacy and safety of this combination, or evidence to suggest one combination is superior to another. We advise using the same considerations you would apply when using other ACE-inhibitor pharmaceuticals.

 

What’s the difference between using this product as an adjunct vs using two ACEIs?       

PreCardix® has a similar MOA as an ACEI pharmaceutical but is not associated with some of the serious side effects of ACEI medication.

PreCardix® reduced blood pressure with a comparable level to ACEI pharmaceuticals in the clinical trial but with no occurrences of dry cough, itching, edema, hypotension, hyperkalemia, or kidney impairment.

For patients who need additional blood pressure support but are experiencing side effects, PreCardix® may be a treatment to consider.

 

Is the use of PreCardix® contraindicated with any medications or supplements?  

PreCardix® has not been directly studied in combination with medications including anti-hypertensive drug treatment. The interactions below are inferred based on ACE inhibitor pharmaceuticals3 but have not been confirmed in clinical research and additional interactions may occur. Patients combining PreCardix® with medications should be closely monitored by their physician for potential interactions.

  • No hypotension was reported in the clinical trials with PreCardix® but hypotension is a common adverse effect after the first dose of an alpha-blocker in combination with a pre-existing ACE-inhibitor, patients on these combinations should be closely monitored.
  • There is no evidence that PreCardix® increases serum potassium levels but due to its ACE-inhibitor action, use caution when combining with other agents that increase serum potassium. This includes; potassium-sparing diuretics, potassium supplements and potassium-containing salts. Serum potassium levels should be monitored frequently in these patients.
  • Use PreCardix® with caution in patients currently on allopurinol. A causal relationship may exist between ACE-inhibitors and allopurinol, predisposing patients to hypersensitivity reactions.
  • The use of NSAIDs and corticosteroids may antagonize the antihypertensive effect of ACE inhibitor medications. Patients who are using NSAIDs or corticosteroids regularly along with PreCardix® should be monitored frequently.
  • ACE-inhibitors augment the systemic effects of intravenous iron, use caution when administering I.V. iron to patients on PreCardix®. Oral administration of iron is not a concern.
  • Patients on concurrent lithium and ACE-inhibitors should have their serum lithium levels monitored regularly. ACE inhibitor medication may decrease renal elimination of lithium leading to lithium toxicity (CNS symptoms, ECG changes, renal failure). PreCardix® has not been studied alongside lithium medication however considering using it with caution.
  • PreCardix® has not been studied in individuals who consume more than 14 alcoholic drinks a week or in those using illicit drugs including the use of tobacco and nicotine.”

 

Are there interactions with Warfarin or any other drugs?           

Marealis Health did not conduct studies on the use of PreCardix® in combination with medications. We advise applying the same cautions and considerations in terms of interactions that you would apply to pharmaceutical ACE-inhibitors. The drug interactions below are inferred based on ACE inhibitor pharmaceuticals, and other drug interactions may occur. Healthcare practitioners should carefully monitor patients combining PreCardix® with other drugs for potential drug interactions.

  • No hypotension was reported in the clinical trials with PreCardix® but hypotension is a common adverse effect after the first dose of an alpha-blocker in combination with a pre-existing ACE-inhibitor, patients on these combinations should be closely monitored.
  • There is no evidence that PreCardix® increases serum potassium levels but due to its ACE-inhibitor action, use caution when combining with other agents that increase serum potassium. This includes; potassium-sparing diuretics, potassium supplements and potassium-containing salts. Serum potassium levels should be monitored frequently in these patients.
  • Use PreCardix® with caution in patients currently on allopurinol. A causal relationship may exist between ACE-inhibitors and allopurinol, predisposing patients to hypersensitivity reactions.
  • The use of NSAIDs and corticosteroids may antagonize the antihypertensive effect of ACE inhibitor medications. Patients who are using NSAIDs or corticosteroids regularly along with PreCardix® should be monitored frequently.
  • ACE-inhibitors augment the systemic effects of intravenous iron, use caution when administering I.V. iron to patients on PreCardix®. Oral administration of iron is not a concern.
  • Patients on concurrent lithium and ACE-inhibitors should have their serum lithium levels monitored regularly. ACE inhibitor medication may decrease renal elimination of lithium leading to lithium toxicity (CNS symptoms, ECG changes, renal failure). PreCardix® has not been studied alongside lithium medication however considering using it with caution.
  • PreCardix® has not been studied in individuals who consume more than 14 alcoholic drinks a week or in those using illicit drugs including the use of tobacco and nicotine.

 

Is there a guideline that directs physicians on how to wean off pharmaceuticals and replace with PreCardix®? 

At this time there is no specific protocol for coming off anti-hypertensive medications to replace them with PreCardix®. Due to the high degree of interpersonal variability, we can not advise a medication weaning schedule that would cover all of these complexities.

Furthermore, we can’t definitively comment on the safety of combining pharmaceuticals with PreCardix® as there are no pre-clinical or clinical trials on this combination. We do however have case reports and in-market research that show the successful combination of anti-hypertensive medication with PreCardix®, more details can be found here: https://precardix.com/reviews/#stories. 

When adding PreCardix® to a patient’s hypertension treatment plan follow the same principals as additive therapy or when switching medications. We would also recommend close monitoring by the prescribing doctor as there is a theoretical risk of hypotension when combining PreCardix® with blood pressure lowering medication, although this interaction has not been reported in any of the case reports or in-market data we have received.

 

Side Effects and Contraindications        

 

Can someone with a shellfish allergy take PreCardix®?  

PreCardix® should not be used in patients with known shellfish allergies. The active ACE-inhibiting peptides in PreCardix® are derived from the shells of arctic cold-water shrimp.

While the peptide’s small particle size is unlikely to cause an allergic reaction, it is recommended that this product be avoided in those with shellfish allergies.

 

What are the potential side effects of PreCardix®?        

In clinical trials, there have been no major adverse effects associated with PreCardix® use. Mild side effects reported by individual participants include; euphoric mood, fatigue, upper abdominal pain and headache.

Moderate nausea has been reported by patients using PreCardix® in clinical practice.

The most common ACE-inhibitor side effects including; dry cough, itching, edema, hypotension, hyperkaliemia or kidney impairment have not been found with PreCardix® in clinical research.

 

Is PreCardix® safe in pregnancy and breastfeeding?       

PreCardix® has not been studied in pregnancy or breastfeeding. Due to the known teratogenic effects of ACE inhibitors, it is recommended that PreCardix® be avoided throughout the entire gestational period and in women who are breastfeeding.

 

Are there any patients who should avoid taking PreCardix®?     

PreCardix® should be avoided in the following patients; those with a history of angioedema related to previous ACE-Inhibitor use, patients with shellfish allergy, pregnant women and women who are breastfeeding, patients with renal artery stenosis and children (under 18 years old). Patients who are on medications or who have pre-exisiting health conditions should always consult with their healthcare provider before initiating PreCardix®.

 

How do I report suspected side effects?             

Any suspected side effects associated with the use of PreCardix® should be reported to Health Canada. For more information regarding reporting online, by mail or fax visit their Adverse Reaction Reporting website here: http://www.hc-sc.gc.ca/dhpmps/medeff/report-declaration/index-eng.php, or call toll-free at 1-866-234-2345.

 

Is there any information on clearance from the body? Are there any problems with renal or liver dysfunction?          

The PreCardix® clinical trial participants were a healthy baseline population with no co-morbidities. Patients with pre-existing medical conditions, including renal or liver dysfunction, were not studied. Patients with pre-existing co-morbidities should be closely monitored by their physician when initiating PreCardix®.

 A 24-hour collection of urine sodium, urine creatinine, and urine volume happened at baseline and week 8 of the clinical trial study. Serum testing including CBC, glucose, creatinine, an estimate of glomerular filtration rate, sodium, potassium, chloride, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and bilirubin happened at screening and eight weeks. There were no clinically significant differences in the placebo and treatment groups.

Pre-clinical toxicity trials on animal models (rats) found no resulting safety issues or hypotension when subjects received a daily dosage 100 times higher than that recommended.

 

Mechanism of action and clinical pharmacology

 

How does PreCardix® work?     

The bioactive peptides isolated from cold-water shrimp shells act as natural ACE-inhibitors. They act on the Renin-Angiotensin-Aldosterone System by blocking the activity of Angiotensin-Converting Enzyme (ACE). This prevents the conversion of Angiotensin 1 to Angiotensin 2 thereby reducing blood pressure. PreCardix® can safely reduce blood pressure in patients with mild to moderate hypertension.

 

How does PreCardix® have the same MOA as ACEI medication but not the same side effect profile?

PreCardix® is a unique composition of thousands of bioactive marine peptides derived from the shells of arctic cold-water shrimp. These short-chain peptides are isolated through a proprietary hydrolysis process.

It is hypothesized by the PreCardix® research and development team that this unique combination of peptides mitigates the adverse effects seen with single-molecule ACE-inhibitors. It should be noted that this is a theory and further research on peptide-specific mechanisms of action is being conducted.

 

Can PreCardix® cause an overdose reaction if over 2 tablets are taken daily?   

In clinical trials, PreCardix® did not cause hypotension in any of the subjects. Once blood pressure reached healthy levels, blood pressure numbers stabilized without decreasing further. These results are consistent with the in-market data. In animal studies (rats), doses 100x the reccomended daily dose did not cause hypotension or other overdose reactions.

Reference: Aluko, R., 2018. Food protein-derived peptides: Production, isolation, and purification. Proteins in Food Processing, [online] pp.389-412

 

Research and Efficacy   

 

Is PreCardix® supported by clinical research?    

The blood pressure-lowering effect of PreCardix® is supported by peer-reviewed clinical research that has been published in the Journal of Hypertension.

A randomized, double-blind, placebo-controlled trial assessed the impact of PreCardix® on daytime ambulatory systolic blood pressure and in-office blood pressure over 8 weeks. The study reported an average reduction in systolic blood pressure of 9.5 mmHg and a 4.2 mmHg reduction in diastolic blood pressure after 8 weeks of treatment.

The full trial is available for review here: https://www.hindawi.com/journals/ijhy/2019/2345042/

 

What is the anticipated blood pressure lowering effect patients can expect with the use of PreCardix®?      

The blood pressure lowering effect of PreCardix® is comparable to that of pharmaceutical ACE inhibitors. In clinical trials, 89% of participants saw significant reductions in their blood pressure within 8 weeks of use. In those 8 weeks, the average reduction in systolic blood pressure was 9.5 mmHg and the average reduction in diastolic blood pressure was 4.2 mmHg. These were signifcant reductions compared to both baseline and placebo.

43% of participants had a reduction in their systolic blood pressure greater than 10 mmHg and 24% had a reduction over 15 mmHg in systolic blood pressure.

 

Were any studies conducted on renal or hepatic patients? Is it safe to use with those patients?

PreCardix® was not studied in patients with pre-existing medical conditions, including renal or hepatic concerns. Clinical trials to date were completed on a healthy baseline population with no co-morbidities only.

In the clinical trial, Marealis Health measured urine for a 24-hour collection for urine sodium, urine creatinine, and urine volume at baseline and week 8 of the study. Serum testing of CBC, glucose, creatinine, estimated glomerular filtration rate, sodium, potassium, chloride, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and bilirubin was performed at screening and eight weeks. There were no clinically significant differences in any of these parameters in both the placebo and treatment groups.

 

Can PreCardix® provide any protection to end organ damage? 

Existing clinical research has not looked at the potential for PreCardix® to protect against end-organ damage. There were no changes to kidney or liver markers between baseline and eight weeks in the clinical trial participants.

 

In the future, will PreCardix®  be considering morbidity/mortality evidence?             

Research on the impact PreCardix® may have on morbidity and mortality will hopefully be conducted in the future.

 Our next phase of research will study the potential mechanism behind the low side effect profile of PreCardix® despite a similar MOA to an ACEI.

We plan to test the current hypothesis set forth by our research and development team that the unique peptides within PreCardix® work synergistically, with some acting as an ACEI and lowering blood pressure, while others prevent unwanted side effects.