Dietary Oxalate Loading Impacts Monocyte Metabolism and Inflammatory Signaling in Humans.

Diet has been associated with several metabolic diseases and may impact immunity. Increased consumption of meals with high oxalate content may stimulate urinary calcium oxalate (CaOx) crystals, which are precursors to CaOx kidney stones. We previously reported that CaOx stone formers have decreased monocyte cellular bioenergetics compared to healthy participants and oxalate reduces monocyte metabolism and redox status in vitro. The purpose of this study was to investigate whether dietary oxalate loading impacts monocyte cellular bioenergetics, mitochondrial complex activity, and inflammatory signaling in humans. Healthy participants (n = 40; 31.1 ± 1.3 years) with a BMI of 24.9 ± 0.6 kg/m2 consumed a controlled low oxalate diet for 3 days before drinking a blended preparation of fruits and vegetables containing a large amount of oxalate. Blood and urine were collected before (pre-oxalate) and for 5 h after the oxalate load to assess urinary oxalate levels, monocyte cellular bioenergetics and mitochondrial complex activity, and plasma cytokine/chemokine levels. Urinary oxalate levels significantly increased in post-oxalate samples compared to pre-oxalate samples. Monocyte cellular bioenergetics, mitochondrial complex I activity, and plasma cytokine and chemokine levels were altered to varying degrees within the study cohort. We demonstrate for the first time that dietary oxalate loading may impact monocyte metabolism and immune response in a cohort of healthy adults, but these response are variable. Further studies are warranted to understand oxalate mediated mechanisms on circulating monocytes and how this potentially influences CaOx kidney stone formation. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03877276.

Effect of alanine supplementation on oxalate synthesis.

The Primary Hyperoxalurias (PH) are rare disorders of metabolism leading to excessive endogenous synthesis of oxalate and recurring calcium oxalate kidney stones. Alanine glyoxylate aminotransferase (AGT), deficient in PH type 1, is a key enzyme in limiting glyoxylate oxidation to oxalate. The affinity of AGT for its co-substrate, alanine, is low suggesting that its metabolic activity could be sub-optimal in vivo. To test this hypothesis, we examined the effect of L-alanine supplementation on oxalate synthesis in cell culture and in mouse models of Primary Hyperoxaluria Type 1 (Agxt KO), Type 2 (Grhpr KO) and in wild-type mice. Our results demonstrated that increasing L-alanine in cells decreased synthesis of oxalate and increased viability of cells expressing GO and AGT when incubated with glycolate. In both wild type and Grhpr KO male and female mice, supplementation with 10% dietary L-alanine significantly decreased urinary oxalate excretion ~30% compared to baseline levels. This study demonstrates that increasing the availability of L-alanine can increase the metabolic efficiency of AGT and reduce oxalate synthesis.

Fish oil supplementation and urinary oxalate excretion in normal subjects on a low-oxalate diet.

OBJECTIVE: To determine if fish oil supplementation reduces endogenous oxalate synthesis in healthy subjects. MATERIALS AND METHODS: Fifteen healthy non-stone-forming adults participated in this study. Subjects first abstained from using vitamins, medications, or foods enriched in omega-3 fatty acids for 30 days. Next, they collected two 24-hour urine specimens while consuming a self-selected diet. Subjects consumed an extremely low-oxalate and normal-calcium diet for 5 days and collected 24-hour urine specimens on the last 3 days of this diet. Next, the subjects took 2 fish oil capsules containing 650-mg eicosapentaenoic acid and 450-mg docosahexaenoic acid twice daily for 30 days. They consumed a self-selected diet on days 1-25 and the controlled diet on days 26-30. Twenty-four-hour urine samples were collected on days 28-30. Excretion levels of urinary analytes including oxalate and glycolate were analyzed. RESULTS: Although there was a significant reduction in urinary oxalate, magnesium, and potassium excretions and an increase in uric acid excretion during the controlled dietary phases compared with the self-selected diet, there were no significant differences in their excretion during controlled diet phases with and without fish oil supplementation. CONCLUSION: These results suggest that fish oil supplementation does not reduce endogenous oxalate synthesis or urinary oxalate excretion in normal adults during periods of extremely low oxalate intake. However, these results do not challenge the previously described reduction in urinary oxalate excretion demonstrated in normal subjects consuming a moderate amount of oxalate in conjunction with fish oil.

Impact of dietary calcium and oxalate, and Oxalobacter formigenes colonization on urinary oxalate excretion.

PURPOSE: Enteric colonization with Oxalobacter formigenes, a bacterium whose main energy source is oxalate, has been demonstrated to decrease the risk of recurrent calcium oxalate kidney stone formation. We assessed the impact of diets controlled in calcium and oxalate contents on urinary and fecal analytes in healthy subjects who were naturally colonized with O. formigenes or not colonized with O. formigenes. MATERIALS AND METHODS: A total of 11 O. formigenes colonized and 11 noncolonized subjects were administered diets controlled in calcium and oxalate contents. We assayed 24-hour urine collections and stool samples obtained on the last 4 days of each 1-week diet for stone risk parameters and O. formigenes levels. Mixed model analysis was used to determine the effects of colonization status on these variables. RESULTS: Urinary calcium and oxalate excretion were significantly altered by the dietary changes in O. formigenes colonized and noncolonized individuals. Mixed model analysis showed significant interaction between colonization status and oxalate excretion on a low calcium (400 mg daily)/moderate oxalate (250 mg daily) diet (p = 0.026). Urinary oxalate excretion was 19.5% lower in O. formigenes colonized subjects than in noncolonized subjects on the low calcium/moderate oxalate diet (mean ± SE 34.9 ± 2.6 vs 43.6 ± 2.6 mg, p = 0.031). CONCLUSIONS: Results suggest that O. formigenes colonization decreases oxalate excretion during periods of low calcium and moderate oxalate intake.