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Oxalate formation from ascorbic acid

Award Number: R01DK126774
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Oxalate formation from ascorbic acid - Project Summary Calcium oxalate stone disease occurs in nearly 10% of the U.S. population and contributes significantly to health care costs and negatively impacts quality of life. The amount of oxalate excreted in urine is a known risk factor for calcium oxalate stone disease. Approximately 50% of urinary oxalate is derived from the diet and the remaining from endogenous synthesis. The metabolism of ascorbic acid (AA), an important antioxidant, is a source of urinary oxalate derived from endogenous synthesis. However, the contribution of this source to urinary oxalate excretion is not well defined. Prior experiments have been hampered by 1) a lack of control of dietary oxalate to urinary oxalate excretion and 2) the confounding generation of oxalate from AA in non- acidified urine samples. The turnover of AA each day is approximately 80 mg and could feasibly result in the formation of up to 40 mg of oxalate per day. We have measured the contribution of AA turnover to urinary oxalate excretion with carbon-13 labelled AA oral dosing in a small number of normal adults and have confirmed that AA contributes 40 -50 % of the endogenous oxalate excreted in urine. These preliminary findings suggest AA turnover is a major source of urinary oxalate derived from endogenous synthesis. In this proposal we will assess the conversion of AA to oxalate in non-stone forming adults and CaOx stone forming adults using the stable isotope of AA, carbon-13 AA. We will further examine the effects of obesity, which is known to be associated with systemic oxidative stress and a decreased plasma AA concentration, on this conversion as well as increased oxalate excretion. Subjects in nutritional studies will ingest known amounts of food-derived AA in diets also controlled in their contents of oxalate, calcium and other nutrients. Experiments will be conducted in cultured cells and mouse models to systematically examine the relationships between AA and oxalate, the role of pro-oxidants in this process, the role of mitochondria and AA transport into this organelle, and to determine whether antioxidants can blunt oxalate formation from AA. If these studies are successful they will open new avenues of research for decreasing urinary oxalate excretion and kidney stone formation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $598,218 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/4/2024	NON-COMPETING CONTINUATION	$598,218
														Subtotal = $598,218

Issue Date FY: 2023 ( Subtotal = $623,143 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/2/2023	NON-COMPETING CONTINUATION	$623,143
														Subtotal = $623,143

Issue Date FY: 2022 ( Subtotal = $623,143 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	3/31/2022	NON-COMPETING CONTINUATION	$62,315
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	3/3/2022	NON-COMPETING CONTINUATION	$560,828
2022	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/24/2021	NEW	$0
														Subtotal = $623,143

Issue Date FY: 2021 ( Subtotal = $623,143 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/18/2021	NEW	$623,143
														Subtotal = $623,143

Grand Total All Awards = $2,467,647

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Oxalate formation from ascorbic acid

Award Number: R01DK126774

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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