Executive Summary
UPLAR
New Application Management Policy
We will also be hosting a free webinar this Thursday, August 12, at 1:00 PM Eastern Time. The webinar should not last longer than 30 minutes. The webinar will cover everything important pertaining to the new regulations and will outline all necessary steps to obtain your ENs. We strongly encourage you to attend this session.To join the webinar please click on the following link several minutes prior to the starting time.
Topic: UPLAR Update Webinar
Date: Thursday, August 12, 2010
Time: 1:00 pm, Eastern Daylight Time (New York, GMT-04:00)
Meeting Number: 572 802 082
Meeting Password: Nhpd2010
To join the online meeting:
1. Go to https://dicentra.webex.com/dicentra/j.php?ED=153124192&UID=0&PW=NNzIxODBhZDIw&RT=NCMxMQ%3D%3D
2. If requested, enter your name and email address.
3. If a password is required, enter the meeting password: Nhpd2010
4. Click “Join”.
As of August 4, 2010, the new Unprocessed Product License Application Regulations (UPLAR) have passed and will be published in Canada Gazette Part II (http://www.gazette.gc.ca/rp-pr/p2/index-eng.html).
The regulations provide a temporary solution for:
natural health products that have submitted a complete product license application, been issued a submission number, and after 180 days are still awaiting a licensing decision,
new product license applications eligible for the exemption after 180 days if no licensing decision is made.
Upon receiving ENs, companies will be allowed to legally sell their products in Canada.
For products which have been in queue for 180 calendar days or more as of August 4, 2010:
These products are eligible for ENs, provided they do meet any of the risk criteria. In order to receive your ENs, you will need to fill out and submit an Exemption Number Fax-Back Form to the NHPD within 60 days of August 4, 2010. Applicants who do not return the fax back form within the 60 days will not receive ENs for these products.
For products which have been in queue for less than calendar 180 days as of August 4, 2010:
These products are not currently eligible for ENs. Once they have been in queue for 180 days, then they will be eligible to receive ENs. The beginning of the 180 day waiting period starts when the applicant receives a submission number for the application. The NHPD has provided a Fax-Back Form which will allow your product to automatically receive an EN once it reaches the 180 day mark. If the Fax-Back Form is not filed pre-emptively, the applicant will have 60 calendar days to return the completed fax back form to receive the EN once the product has been in queue for 180 days. If the completed fax back form is not returned to the NHPD by the 60 day deadline, then the NHPD will assume that the applicant does not want their product to be exempted.
For products which have been submitted, but have not received a submission number as of August 4, 2010:
Products which have not received a submission number as of yet will be eligible for pre-emptive opt-in and will receive a Fax-Back Form along with their application acknowledgement letter. The completion and return of the pre-emptive Fax-Back Form will allow the product to automatically receive an EN after 180 days in queue, provided that the product is eligible for an EN. Please note that submission numbers will now be used for administration purposes only as a method to track the application and determine when the 180 day count begins. The new application acceptance letter will replace the submission number and will include:
if the product is eligible for an exemption;
what the exemption number would be for that product;
the date on which the product would be eligible for an exemption;
what is needed to apply for an exemption; and
the fact that a complete Fax-Back Form must be submitted within 60 calendar days of the eligibility date
For all products, the EN becomes valid only when the EN number appears in the Natural Health Products Exempted Products Database (http://webprod3.hc-sc.gc.ca/product-produit/search-rechercheReq.do?lang=eng). Applicants are responsible for checking the database for the presence of their product and EN. Included in the database entry are the EN, Company Name, Brand Name, Dosage Form, Status (valid, not valid or licensed) and Status Date. The information should appear in the database 5 calendar days after submitting the Fax-Back Form.
The following types of products will not be eligible to receive an EN:
Products in queue which have been deemed ineligible to receive ENs can be revised in order to obtain ENs. Changes made to the PLA and label may include the removal of a subpopulation or ingredient and revised PLA and label should be submitted to your Submission Coordinator. Then when the Fax-Back Form is filed with the NHPD, the revised product will receive its EN after 180 days in queue.
Once a product has received its EN, a notification may be filed outlining changes to the application which do not to impact the safety, efficacy and/or quality of the product, including:
If any of the above changes are made to an exempt NHP, exemption number holders should consult NHPD’s Post-Licensing Guidance Document – http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/plgd_psdldr_2-eng.php– for information on how to submit a notification to NHPD.
Please note that an EN may remain valid for up to 30 months from August 4, 2010, provided that a license is not granted prior to the 30 month end point. Furthermore, the EN must appear on the label within a reasonable amount of time, i.e. the lesser of the next label run or 12 months.
Under these regulations, products with ENs are subject to the NHPR, including key on-market safety oversight provisions. Some examples of these provisions include: adverse reaction reporting, good manufacturing practices, site licensing, the ability for the Minister to order a stop sale, and recall reporting requirements. Please note that site information must be provided to Health Canada before the sale of an NHP begins.
A new Compliance and Enforcement Policy for NHPs has come into effect along with the new UPLAR with a 6 month educational period. The full legislature comes into effect February 2011 meaning that at this point a product which is being sold without an EN, NPN or DIN-HM will be subject to enforcement procedures, such as a stop sale or recall. Prior to February 2011, products being sold without ENs, NPNs or DIN-HMs will not be subject to stop sales or product recalls, instead the government will provide education on how to come into compliance with the NHPR.
As of August 4, 2010, the new Unprocessed Product License Application Regulations (UPLAR) have passed and will be published in Canada Gazette Part II (http://www.gazette.gc.ca/rp-pr/p2/index-eng.html).
The regulations provide a temporary solution for:
natural health products that have submitted a complete product license application, been issued a submission number, and after 180 days are still awaiting a licensing decision,
new product license applications eligible for the exemption after 180 days if no licensing decision is made.
Upon receiving ENs, companies will be allowed to legally sell their products in Canada.
For products which have been in queue for 180 calendar days or more as of August 4, 2010:
These products are eligible for ENs, provided they do meet any of the risk criteria. In order to receive your ENs, you will need to fill out and submit an Exemption Number Fax-Back Form to the NHPD within 60 days of August 4, 2010. Applicants who do not return the fax back form within the 60 days will not receive ENs for these products.
For products which have been in queue for less than calendar 180 days as of August 4, 2010:
These products are not currently eligible for ENs. Once they have been in queue for 180 days, then they will be eligible to receive ENs. The beginning of the 180 day waiting period starts when the applicant receives a submission number for the application. The NHPD has provided a Fax-Back Form which will allow your product to automatically receive an EN once it reaches the 180 day mark. If the Fax-Back Form is not filed pre-emptively, the applicant will have 60 calendar days to return the completed fax back form to receive the EN once the product has been in queue for 180 days. If the completed fax back form is not returned to the NHPD by the 60 day deadline, then the NHPD will assume that the applicant does not want their product to be exempted.
For products which have been submitted, but have not received a submission number as of August 4, 2010:
Products which have not received a submission number as of yet will be eligible for pre-emptive opt-in and will receive a Fax-Back Form along with their application acknowledgement letter. The completion and return of the pre-emptive Fax-Back Form will allow the product to automatically receive an EN after 180 days in queue, provided that the product is eligible for an EN. Please note that submission numbers will now be used for administration purposes only as a method to track the application and determine when the 180 day count begins. The new application acceptance letter will replace the submission number and will include:
if the product is eligible for an exemption;
what the exemption number would be for that product;
the date on which the product would be eligible for an exemption;
what is needed to apply for an exemption; and
the fact that a complete Fax-Back Form must be submitted within 60 calendar days of the eligibility date
For all products, the EN becomes valid only when the EN number appears in the Natural Health Products Exempted Products Database (http://webprod3.hc-sc.gc.ca/product-produit/search-rechercheReq.do?lang=eng). Applicants are responsible for checking the database for the presence of their product and EN. Included in the database entry are the EN, Company Name, Brand Name, Dosage Form, Status (valid, not valid or licensed) and Status Date. The information should appear in the database 5 calendar days after submitting the Fax-Back Form.
The following types of products will not be eligible to receive an EN:
Products in queue which have been deemed ineligible to receive ENs can be revised in order to obtain ENs. Changes made to the PLA and label may include the removal of a subpopulation or ingredient and revised PLA and label should be submitted to your Submission Coordinator. Then when the Fax-Back Form is filed with the NHPD, the revised product will receive its EN after 180 days in queue.
Once a product has received its EN, a notification may be filed outlining changes to the application which do not to impact the safety, efficacy and/or quality of the product, including:
If any of the above changes are made to an exempt NHP, exemption number holders should consult NHPD’s Post-Licensing Guidance Document – http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/plgd_psdldr_2-eng.php– for information on how to submit a notification to NHPD.
Please note that an EN may remain valid for up to 30 months from August 4, 2010, provided that a license is not granted prior to the 30 month end point. Furthermore, the EN must appear on the label within a reasonable amount of time, i.e. the lesser of the next label run or 12 months.
Under these regulations, products with ENs are subject to the NHPR, including key on-market safety oversight provisions. Some examples of these provisions include: adverse reaction reporting, good manufacturing practices, site licensing, the ability for the Minister to order a stop sale, and recall reporting requirements. Please note that site information must be provided to Health Canada before the sale of an NHP begins.
A new Compliance and Enforcement Policy for NHPs has come into effect along with the new UPLAR with a 6 month educational period. The full legislature comes into effect February 2011 meaning that at this point a product which is being sold without an EN, NPN or DIN-HM will be subject to enforcement procedures, such as a stop sale or recall. Prior to February 2011, products being sold without ENs, NPNs or DIN-HMs will not be subject to stop sales or product recalls, instead the government will provide education on how to come into compliance with the NHPR.
What Health Canada’s Post-Market Surveillance Program Means to You as a Market Authorization Holder (MAH)
Canada Vigilance is Health Canada’s post-market surveillance program operated by the Marketed Health Products Directorate (MHPD). Canada Vigilance collects and assesses adverse reaction (ARs) to marketed health products including natural health products (NHPs). The collection of ARs and the monitoring thereof remain a viable means of identifying previously unrecognized, rare or serious ARs. This may result in changing product safety information, facilitating decisions on regulatory actions such as withdrawal of a product from the Canadian market, contributing to international data regarding risks and effectiveness of health products, and imparting health product safety knowledge that benefits all Canadians.
There are many stakeholders involved in the reporting of ARs, including the manufacturers of health products, known as Market Authorization Holders (MAHs). MAHs are required to submit serious adverse reaction reports to the Canada Vigilance Program when they become aware of a serious adverse reaction to a product as outlined in the Canada Food and Drugs Act and the Natural Health Products Regulations. The MAH must also, on an annual basis, prepare and maintain a Summary Report that contains a concise and critical analysis of all domestic ARs to an NHP, and all foreign serious unexpected ARs to an NHP taken at the recommended dose reported during the previous 12 months.
The Summary Report is maintained by the MAH, and when requested by Health Canada, must be submitted to the MHPD within 30 calendar days. In addition to complying with regulatory requirements to report safety and efficacy information, Health Canada expects that MAHs inform MHPD if the MAH concludes from the annual Summary Report that there is a significant change in the risk-benefit profile of a product relating to its safe use.
For more information, please read the “Frequently Asked Questions” that follow, and if you are unclear on your responsibilities or would like to enlist our expert aide, please contact us! dicentra will be hosting a brand new webinar on Adverse Reaction Reporting this coming fall, details will be on our website soon!
How does Health Canada (HC) collect post-market surveillance data?
HC collects post-market surveillance data through Canada Vigilance, a program of MedEffect™ Canada. HC’s post-market surveillance program collects and assesses AR reports for the following marketed health products:
· pharmaceuticals,
· biologics,
· natural health products, and
· radiopharmaceuticals.
Central to the Canada Vigilance Program is its AR database. The Canada Vigilance database consists of a core application for collecting, coding, assessing and reporting both domestic and foreign AR data. It is a signal-detection and data-mining tool, and one of its modules automatically routes AR cases to specialists and assessors. The database is fully compliant with the International Conference on Harmonisation’s (ICH’s) technical requirements and is bilingual.
What post-market data must be reported to Health Canada regarding NHPs?
-Serious adverse reactions inside Canada: mandatory case report within 15 days
-Serious unexpected adverse reactions outside Canada: mandatory case report within 15 days
-All adverse reactions: recorded and critically analyzed in a Summary Report, prepared annually
Note: It is not mandatory to submit the Summary Report to HC – however, if requested by HC, the report is required to be submitted within 30 business days
For natural health products, MAHs must submit domestic and foreign AR reports to the MHPD as set out in Section 24 of the Natural Health Products Regulations once their health product is licensed to be marketed in Canada.
When Health Canada requests the annual summary report, it is preferred that it be submitted in the Periodic Safety Update Report (PSUR) format in accordance with the standards defined in the ICH E2C(R1)10 guideline.
MAHs may also use an annual summary report format. This annual summary report format does not contain information regarding the worldwide market authorization status and completed and planned studies, both of which are included in the PSUR format.
Must the Annual report describe ARs by product or by ingredient?
Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate justification. Alternate approaches should be discussed in advance with the relevant program area to avoid the possible
finding that applicable statutory or regulatory requirements have not been met.
For natural health products, it is important to include the Latin binomial, author reference, family, type of extract (e.g., aqueous versus alcoholic, including percent of solvent), part of the plant used (in the case of an herbal product), ingredients and quantity of each (for combination products – the suspected ingredient), and potency (for homeopathic products).
Depending on the health product or circumstances, it may be useful or practical to have more than one line listing, such as for different dosage forms or indications, if such differentiation facilitates presentation and interpretation of the data.
What are the responsibilities of the Market Authorization Holders (companies authorized to market health products) for monitoring the safety and therapeutic effectiveness of their products (which extends to post-market as well)?
They must advise stakeholders, including consumers, health professionals and regulators, of changes in the benefit/risk balance of their products. They must have continued monitoring of ARs in the post-market phase – or adverse incidents in the case of medical devices. Continued monitoring is essential for maintaining a comprehensive safety and effectiveness profile of health products available to Canadians. Mandatory reporting by Market Authorization Holders provides both domestic and foreign AR information to Health Canada.
How does Health Canada monitor regulated product safety internationally?
Health Canada monitors regulated product safety through an International Collaboration. MHPD staff collaborates with leading foreign regulatory partners through Memoranda of Understanding (MOUs), especially regarding the effective sharing of confidential and personal information on regulated product safety. A regular video/teleconference with federal regulatory partners in the United States, New Zealand and Australia enables the sharing of ongoing federal regulatory post-market surveillance / vigilance issues. Where possible, MHPD and its MOU partners collaborate on risk communications requiring simultaneous action to reduce public confusion.
|
Date MOU Signed |
Country/Region |
Name of the Organization |
| December 2007 | European Union | European Commission’s Directorate-General Enterprise and Industry & European Agency for the Evaluation of Medicinal Products |
| October 2006 | Switzerland | Swissmedic |
| September 2006 | Singapore | Health Science Authority |
| November 2003 | Australia | Therapeutic Goods Administration |
| November 2003 | United States | Food and Drug Administration |
| September 1999 | China State | Food and Drug Administration of China |
How frequently does Health Canada provide safety updates to health professionals?
The Canadian Adverse Reaction Newsletter (CARN), a quarterly publication since 1991, alerts health professionals to potential signals detected through the review of case reports submitted to Health Canada. CARN provides subscribers with early information on suspected ARs to health products before comprehensive risk/benefit evaluations and regulatory decisions are undertaken. CARN is available on the MedEffect™ Canada Web site by subscribing to the MedEffect™ e-Notice.
How frequently is the Canada Vigilance Online Database updated?
On a quarterly basis, the MedEffect™ Canada Web site is updated with the latest adverse reaction reports, so that the public has access to ARs that have been reported to Health Canada. The information on the MedEffect™ Canada Web site is a subset of the actual data contained within the Canada Vigilance AR database.
Is there a worldwide governing body that collects worldwide ARs?
MHPD continues the work of those who were among the founding members of the WHO International Drug Monitoring program in 1968. Canada is one of 180 member countries and is ranked fourth in the rate of submission of domestic AR reports to the WHO vigilance database, which is located at the Uppsala Monitoring Centre in Sweden.
MHPD is engaged in developing better collaboration and work-sharing opportunities with other regulators internationally. This approach is consistent with that of the HPFB of Health Canada.
To date, MHPD has been an observer in the ICH of Technical Requirements for Registration of Pharmaceuticals for Human Use and applied their post-market surveillance standards in the development of the Canada Vigilance database; has participated in the Council for International Organizations of Medical Science VIII working group report on signal detection development and in the International Society on Pharmacogivilance; has held regular four-way video-conference meetings with the U.S.
Food and Drug Administration (FDA), Australian Therapeutic Goods Administration (TGA)
How is the AR information processed?
AR reports are analyzed to discover potential health product safety signals. A signal is considered to be the preliminary indication of a product-related issue. The identification of a signal is not by itself the proof of the association of an AR to a health product, but it triggers the need to further investigate a potential association. Signals must be carefully evaluated in order to confirm or to disprove the potential association between the product and the AR.
Need more info? More information on natural health products, the new NHP Regulations, and guidance on interpreting and using this information can be found on Health Canada’s website at http://www.hc-sc.gc.ca/index-eng.php.
In order to fulfill dicentra’s mission to serve the natural health products industry as a source for education and trusted scientific and regulatory information, we now offer free quarterly regulatory updates (every 3 months) through an online webinar.
These webinars are meant to keep you and all of your fellow coworkers up-to-date on the latest issues pertaining to scientific and regulatory affairs. The main focus of each webinar will be for anything important pertaining to natural health products and their regulations in Canada. Examples include a summary of the Natural Health Products Directorate’s status of submissions reports, the latest regulatory status of ingredients, new published monographs, and all other important issues. We will also cover major issues related to other product categories that may have an effect on natural health products.
All webinars are presented by a qualified member of our team and will last approximately 30 minutes. Sit back and enjoy our interpretation and navigation to help propel your business forward at no cost. Remaining dates for 2010 are as follows:
Wednesday, September 29, 2010, 1:00 PM Eastern Time
Wednesday, December 8, 2010, 1:00 PM Eastern Time
Visit www.dicentra.ca/updates to register now!
Our most recent webinar in this series occured on June 23rd, 2010. To view the video of this presentation please visit our website at http://www.dicentra.ca/NHP_Regulatory_Update_Q2_2010.html.
Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, Okano M, Kagoshima M, Tsuchida T. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr. 2010 Jun;64(6):636-43.
Probiotics are live microorganisms that when administered in adequate amounts confer a health benefit to the host. Recently, probiotics have been administered in fermented milk products. Lactobacillus gasseri SBT2005 (LG2055) is a probiotic that originates from human intestine and has been selected for its ability to improve the intestinal environment. The organism demonstrates bile tolerance, bile acid conjugation as well as cholesterol binding to produce a cholesterol lowering effect in humans suffering from mild hypercholesterolemia. A multicentred, randomized placebo-controlled study was conducted to assess the anti-obesity effects of LG2055 in healthy adults. Clinical outcome measures include abdominal fat area, body weight and serum adiponectin, a hormone involved in fatty acid catabolism. Following a 4 week lead-in period, fermented milk containing 5 x 1010 cfu/100g of LG2055 was administered to participants twice daily for 12 weeks. When compared to the control group, significant decreases in the treatment group were observed at weeks 8 and 12 for body weight, BMI, hip, waist-to-hip ratio and fat mass. At week 12, probiotic administration was associated with a significant decrease in visceral, subcutaneous and total fat area when compared to baseline levels. Moreover, significant decreases in body weight, BMI, waist circumference were observed at weeks 8 and 12 when compared to baseline levels. Probiotic supplementation was also associated with no changes in adiponectin levels, whereas the control group experienced increases in adiponectin levels. Overall, this study suggests that probiotic LG2055 is beneficial effect on abdominal adiposity and body weight measures.
Schütz K, Saß M, de With A, Graubaum HJ, Grünwald J. Immune-modulating efficacy of a polyphenol-rich beverage on symptoms associated with the common cold: a double-blind, randomised, placebo-controlled, multi-centric clinical study. Br J Nutr. 2010 May 21:1-9.
The common cold is the most frequent infectious disease in humans. The majority of adults are affected by the disease 2-3 times per year. Symptoms often start with headache, sneezing, chills, sore throat and then progress to nasal discharge, nasal obstruction, cough and a general feeling of sickness. The health promoting potentials of polyphenols and polysaccharides are mainly attributed to the immunostimulative, antiviral, anti-inflammatory and antioxidative activity. A randomized, double-blind, multicentred clinical trial was conducted to evaluate a polyphenol-rich beverage containing green tea, grape seed, grape skin, and shiitake mushroom extract on the reduction of cold symptoms. Ninety-eight volunteers suffering from the common cold were recruited for the study. Inclusion criteria were that the subject must achieve a score of 5 for their severity of cold symptoms including headache, joint pains, sore throat/difficulty swallowing, hoarseness/cough, nasal congestion in addition to 1 cold-related throat condition. The primary efficacy endpoint was defined as a decrease in the total 5 point score. The secondary efficacy measure was the subject becoming “complaint-free” by the end of the study period. No significant adverse reactions were observed during the study. When compared to the placebo-controlled group, significant differences in the severity of cold symptoms were observed following 3-4 days of treatment. At the final examination, 19 out of 49 subjects in the treatment group claimed to be complaint free, whereas only 4 out of 47 in the placebo-controlled group reported to be symptom-free. No significant differences were observed in the use of additional cold therapy between the two test groups. Overall, the subjects receiving the investigational beverage experienced a faster decline in cold-associated symptoms when compared to the placebo-controlled group.
Skarupski KA, Tangney C, Li H, Ouyang B, Evans DA, Morris MC. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Am J Clin Nutr. 2010 Jun 2. [Epub ahead of print].
Depression is the most prevalent mental disorder affecting the US population and is also a key risk factor for numerous other health outcomes. Biochemically, vitamin B6, folate and vitamin B12 are implicated in the metabolism of homocysteine. It is hypothesized that vitamin B6, vitamin B12 and folate deficiencies may lead to elevated homocysteine levels, which is thought to be associated with depression. Skarupski et al. conducted this longitudinal study to investigate the daily consumption of vitamin B12, vitamin B6 and folate in 3503 participants over an average time course of 7.2 years. Depressive symptoms were evaluated based on the 10 item analysis of the Centre for Apidemiologic Studies Depression scale (CES-D) and cognitive function was assessed based on 4 tests: the Symbol Digital Modalities Test and the Mini-Mental State Examination and two separate tests for memory. Higher intakes of the vitamins were associated with higher cognitive processes, particularly in participants with higher levels of education and income. Vitamins B6 and B12 were inversely correlated with depressive symptoms. However, no correlation between folate intake and severity of depressive symptoms was observed. Overall, the results of the study suggest that higher intakes of both vitamin B6 and vitamin B12 may help to prevent the development of depression over an average time period of 7.2 years.
Terushkin V, Bender A, Psaty EL, Engelsen O, Wang SQ, Halpern AC. Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. J Am Acad Dermatol. 2010 Jun;62(6):929.e1-9.
It has been proposed that vitamin D deficiencies may be associated with musculoskeletal disease. Recommendations to achieve adequate serum vitamin D levels include daily supplementation with 1000 IU vitamin D, or exposure of the face, arms and hands to sunlight for adequate lengths of time. This study aimed to assess the length of time a person might need to spend in the sun with 25.5% of their skin exposed to achieve a blood serum levels equivalent to those achieved following oral administration of either 400 IU or 1000 IU of vitamin D. The researchers chose to assess theoretical sunlight parameters in 2 locations: Boston, MA and Miami, FL using a computerized simulation tool. The results of the analysis suggest that in the summer, the amount of sunlight needed to generate the set levels of vitamin D were equivalent between the two cities. However, in the winter, the analysis suggests that there is an insufficient amount of UVB to produce levels upwards of 400 IU in Boston, MA. Which is substantially low compared the 15 min of sun exposure needed in Miami, Fl to generate blood vitamin D levels equivalent to oral administration of 1000 IU. The researchers do address that limitations are associated with results generated by theoretical simulation experiments. However, they conclude that oral supplements of vitamin D are most likely the safest route to achieving adequate vitamin D levels since prolonged sun exposure is associated with various health risks.
Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A. Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans. Role for Nitrite-Derived NO. Hypertension. 2010 Jun 30. [Epub ahead ofprint].
Hypertension is associated with cardiovascular disease which is the leading cause of deaths in North America. Clinical evidence suggests the use of nitrates may be used to control high blood pressure. Furthermore, clinical evidence has suggested that beetroot, a vegetable containing high levels of nitrate, has been implicated in promoting healthy blood pressure levels. This study aimed to assess the effects of inorganic nitrate, from both beetroot juice and potassium nitrate, on blood nitrate/nitrite levels, blood pressure (BP) and endothelial function following ischemia/reperfusion injury. The dose of potassium nitrate administered was equivalent to the nitrite present in 250 ml of beetroot juice (24 mmol nitrate). Three separate studies were conducted to test the effects of each of the test substances against a control. Two randomized open-labelled crossover studies were conducted to assess the effects of either beetroot juice or potassium nitrate (a nitrate-positive control). As a nitrate-negative control, a double-blind crossover study was conducted to assess the effects of potassium chloride in comparison to beetroot juice and potassium nitrate. The results of the trials indicated that a dose-dependent increase in circulating nitrate and nitrite levels were associated with both potassium nitrate and beetroot juice administration. Cyclic GMP (cGMP), the ultimate indicator of NO bioactivity and vasodilation, was increased in both the potassium nitrate- and beetroot juice- supplemented groups. Ischaemia/reperfusion-induced endothelial dysfunction was prevented in both the potassium nitrate and beetroot juice groups when compared to control. However, beetroot juice administration was associated with no changes in diastolic BP and heart rate when compared to placebo-control. No significant changes in any of the measured parameters were observed for potassium chloride when compared to low nitrate-containing water. Overall, this study suggests that beetroot juice was as effective as potassium nitrate in preventing ischaemia/reperfusion-induced endothelial dysfunction and increasing the levels of circulating nitrate/nitrite and cellular levels of cGMP.