WO2021069578A1 - Riboflavin for use in controlling blood pressure during pregnancy - Google Patents
Riboflavin for use in controlling blood pressure during pregnancy Download PDFInfo
- Publication number
- WO2021069578A1 WO2021069578A1 PCT/EP2020/078266 EP2020078266W WO2021069578A1 WO 2021069578 A1 WO2021069578 A1 WO 2021069578A1 EP 2020078266 W EP2020078266 W EP 2020078266W WO 2021069578 A1 WO2021069578 A1 WO 2021069578A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- riboflavin
- blood pressure
- genotype
- during pregnancy
- women
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/174—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
Definitions
- This invention is directed to the use of riboflavin as an active ingredient for controlling blood pressure during pregnancy.
- Hypertension affects up to 15% of all pregnancies and can lead to serious hypertensive disorders which are the major causes of fetal and maternal morbidity and mortality worldwide. Disturbances in one- carbon metabolism have been linked with adverse pregnancy complications, such as gestational hypertension and pre-eclampsia.
- the C677T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetra- hydrofolate reductase (MTHFR) has been implicated in hypertension and hypertension in pregnancy.
- BP blood pressure
- Pregnant women were recruited from antenatal clinics and screened for MTHFR genotype.
- Biomarker status of riboflavin was determined using the functional assay erythrocyte glutathione reductase activation coefficient (EGRac). Of 1709 participants recruited and screened, 11.5% were identified with the variant MTHFR genotype.
- one aspect of this invention is the use of riboflavin for controlling hypertension in pregnant women by administering riboflavin either as a sole medicament or in combination with a known anti-hypertensive agent.
- Preferred daily dosages contain at least 1-10 mg per day.
- riboflavin is generally known to be well tolerated at even high levels, dosages up to and even exceeding 100 mg per day could safely be used.
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Riboflavin can be used during pregnancy to control blood pressure in women having the MTHFR677TT genotype, particularly during the first trimester.
Description
IBOFLAVIN FOR USE IN CONTROLLING BLOOD PRESSURE DURING PREGNANCY
BRIEF DESCRIPTION OF THE INVENTION
This invention is directed to the use of riboflavin as an active ingredient for controlling blood pressure during pregnancy.
BACKGROUND OF THE INVENTION
Hypertension affects up to 15% of all pregnancies and can lead to serious hypertensive disorders which are the major causes of fetal and maternal morbidity and mortality worldwide. Disturbances in one- carbon metabolism have been linked with adverse pregnancy complications, such as gestational hypertension and pre-eclampsia.
The risk of gestational hypertension and pre-eclampsia was shown to be reduced by folic acid supplementation during pregnancy, albeit the evidence is somewhat conflicting. Such inconsistencies might be explained by intra- and inter-population genetic variation.
The C677T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetra- hydrofolate reductase (MTHFR) has been implicated in hypertension and hypertension in pregnancy.
It would be desirable to be able to control blood pressure in pregnant women safely, especially in those women who do not traditionally respond well to commonly used anti-hypertensive agents.
DETAILED DESCRIPTION OF THE INVENTION
We have found that blood pressure (BP) is higher in non-pregnant women of reproductive age with the MTHFR 677TT genotype. Pregnant women were recruited from antenatal clinics and screened for MTHFR genotype. Biomarker status of riboflavin was determined using the functional assay erythrocyte glutathione reductase activation coefficient (EGRac). Of 1709 participants recruited and screened, 11.5% were identified with the variant MTHFR genotype. Within the first trimester, an atypical pattern of BP was observed in these women, in that both systolic and diastolic BP increased from the 8th to 16th gestational week (GW), compared with the expected decrease in BP over this time, as previously reported and found here in women without this polymorphism (CC/CT
genotypes combined). At the 12th GW, after adjusting for maternal and gestational age, women with the TT genotype compared to CC or CT genotypes had significantly higher systolic BP (P 0.026), diastolic BP (P 0.050) and hypertension rate (10.4 vs 4.0 or 5.4%; P 0.048).
When these results were stratified by riboflavin, the BP phenotype owing to this polymorphism was exacerbated among women with suboptimal status (i.e. EGRac>1.26), with median (95% Cl) systolic BP of 118.5 (114.6, 121.5) mmHg compared to 114.5 (111.7, 119.2) mmHg in those with optimal status (EGRac<1.26) within the TT genotype group. We have found that the TT genotype is associated with higher BP during the first trimester of pregnancy and riboflavin may have an important modulating effect on BP in these women.
Thus one aspect of this invention is the use of riboflavin for controlling hypertension in pregnant women by administering riboflavin either as a sole medicament or in combination with a known anti-hypertensive agent. Preferred daily dosages contain at least 1-10 mg per day. As riboflavin is generally known to be well tolerated at even high levels, dosages up to and even exceeding 100 mg per day could safely be used.
EXAMPLES
EXAMPLE 1
EXAMPLE 2
A human clinical trial is run based on the following protocol:
• A randomised controlled trial to investigate the effect of intervention with riboflavin, alone or in combination with 5 MTHF, on blood pressure in pregnant women stratified by MTHFR genotype
• Aims:
• a. To compare Blood Pressure (BP) in pregnancy across the three MTHFR TWΊ genotypes: (observational study)
• Hypothesis: Women with the variant TT genotype will have higher BP in pregnancy and a greater increase in BP from the 16th to the 36th gestational week.
• b. To examine the effect of riboflavin supplementation on BP in pregnant women with the TG genotype (RCT)
• Hypothesis: Riboflavin supplementation will maintain healthier BP in pregnant women with the TG genotype.
• To examine the effect of supplementation with riboflavin in combination with 5 methyltetrahydrofolate (5-MTHF) on BP in pregnant women with the TG genotype (RCT).
• Hypothesis: Combined supplementation, compared to riboflavin alone, will generate a better BP response in TT women.
• c. To compare BP of newborns across the three different MTHFR 677 genotypes.
• Hypothesis: Newborns with the TT genotype will have higher BP than those with the CC genotype
Claims
1. A method of controlling hypertension in a pregnant woman comprising administering a daily dose of riboflavin.
2. A method according to claim 1, further comprising administering an antihypertensive medicament.
3. Use of riboflavin to control hypertension in a pregnant woman.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962913321P | 2019-10-10 | 2019-10-10 | |
| US62/913321 | 2019-10-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2021069578A1 true WO2021069578A1 (en) | 2021-04-15 |
Family
ID=72885516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2020/078266 Ceased WO2021069578A1 (en) | 2019-10-10 | 2020-10-08 | Riboflavin for use in controlling blood pressure during pregnancy |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2021069578A1 (en) |
-
2020
- 2020-10-08 WO PCT/EP2020/078266 patent/WO2021069578A1/en not_active Ceased
Non-Patent Citations (5)
| Title |
|---|
| "Abstracts from the 2019 Annual Scientific Meeting of the British and Irish Hypertension Society (BIHS)", JOURNAL OF HUMAN HYPERTENSION, NATURE PUBLISHING GROUP, GB, vol. 33, no. 1, 16 September 2019 (2019-09-16), pages 1 - 29, XP036886532, ISSN: 0950-9240, [retrieved on 20190916], DOI: 10.1038/S41371-019-0217-8 * |
| CICERO ARRIGO F G ET AL: "Nutraceuticals and Blood Pressure Control: Results from Clinical Trials and Meta-Analyses", HIGH BLOOD PRESSURE & CARDIOVASCULAR PREVENTION : THE OFFICIAL JOURNAL OF THE ITALIAN SOCIETY OF HYPERTENSION, ADIS INTERNATIONAL LTD, NZ, vol. 22, no. 3, 1 September 2015 (2015-09-01), pages 203 - 213, XP009512614, ISSN: 1179-1985, DOI: 10.1007/S40292-015-0081-8 * |
| DATABASE EMBASE [online] ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL; 2017, O'SULLIVAN E ET AL: "Riboflavin, MTHFR 677C->T and blood pressure in pregnant and non-pregnant women", XP002801630, Database accession no. EMB-619736570 * |
| MCNULTY HELENE ET AL: "Riboflavin,MTHFRgenotype and blood pressure: A personalized approach to prevention and treatment of hypertension", MOLECULAR ASPECTS OF MEDICINE, PERGAMON PRESS, OXFORD, GB, vol. 53, 6 October 2016 (2016-10-06), pages 2 - 9, XP029886060, ISSN: 0098-2997, DOI: 10.1016/J.MAM.2016.10.002 * |
| PROCEEDINGS OF THE NUTRITION SOCIETY 2017 CAMBRIDGE UNIVERSITY PRESS NLD, vol. 76, no. OCE3, 2017, pages E51 CONF 20170621 to 20170623 Belfast - Nutrition, ISSN: 1475-2719 * |
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