Oxalates

3.1. Definition 

Oxalate, or oxalic acid, is a substance that can form insoluble salts with minerals, including sodium, potassium, calcium, iron, and magnesium. These compounds are produced in small amounts in both plants, and mammals. All major groups of photosynthetic organisms produce oxalate. It is suggested that plants manufacture oxalate for a variety of functions including calcium regulation, plant protection, and detoxification of heavy metals [51]. In mammals, endogenous oxalate is a metabolite of ascorbate, glyoxylate, hydroxyproline and glycine. Urinary oxalate mostly consists of endogenous oxalate, as opposed to exogenous dietary oxalate. Plant-derived oxalate is available in several different forms; as either water-soluble oxalate (oxalic acid, potassium, sodium and ammonium oxalates) or insoluble oxalate salts (primarily as calcium oxalate) [52]. Soluble (unbound) oxalates can chelate minerals, reducing absorption, or are absorbed through the intestines and colon. Absorbed dietary oxalates are believed to contribute to calcium oxalate kidney stone formation [53]. Insoluble oxalates, on the other hand, are excreted in the feces [54]. Due to their effects on nutrient absorption and possible role in kidney stone formation, oxalates are considered by some to be ‘antinutrients’. Although events of toxicity have occurred in livestock chiefly grazing on oxalate-rich plants [51], a balanced human diet typically contains only small amounts of oxalates [53]. 

3.2. Background 

Oxalates are present in many commonly consumed plant foods. Plant foods with the highest oxalate content include spinach, swiss chard, amaranth, taro, sweet potatoes, beets, rhubarb, and sorrel. Raw legumes, whole grains, nuts, baking cocoa and tea also contain oxalate, though in smaller amounts. Distribution of oxalate within a plant can vary. Leaves (spinach, beet greens) are reported to have far greater oxalate content than stalks (rhubarb) or roots (beets, carrots). A distinction should be made between total oxalate, soluble and insoluble oxalate, as excess soluble oxalate has more of an effect on bioavailability and kidney stone formation [54]. Chai and Liebman reported fresh spinach to contain an average of 1145 mg/100 g fresh weight (FW) total oxalate, 803 mg being in the soluble form, and 343 mg being insoluble oxalate [54]. Another group found spinach to contain 978 mg/100 g FW of total oxalate, 543 mg of that being soluble oxalate [55]. Nuts are also reported to be rich in oxalates, ranging from 42 mg/100 g in raw macadamia nuts, to 140, 262, and 469 mg/100 g in roasted peanuts, cashews and almonds, respectively. Soluble content in peanuts and almonds were found to be 108 mg and 153 mg/100 g [56]. Wheat bran contains a somewhat higher amount of soluble oxalate (113 mg/100 g dry weight (DW)), while whole grain products contain much less (13.8 mg in oats, 44 mg/100 g in whole wheat flour) [57]. Rawlegumes vary widelyin oxalate content. Soybeans contain the greatest amount (370 mg/100 g DW), followed by lentils and peas (168–293 mg/100 g DW), chickpeas (192 mg/100 g DW), and common beans (98–117 mg/100 g DW) [19]. Soluble oxalate in raw chickpeas and lentils is only a fraction of total oxalate [58]. Beet root, another vegetable known for its oxalate content, averages 65 mg/100 g FW of oxalate, with 47 mg being soluble oxalate [54,55]. Differences in total oxalate content is variable among cultivars, season, and growing conditions. For example, among 310 different cultivars of spinach, oxalate concentration ranged from 647.2 to 1286.9 mg/100 g FW, with an average of 984 mg/100 g [59]. Savage et al., on the other hand, found only 266.2 mg/100 g FW in New Zealand grown spinach [53]. Horner and colleagues found over a two-fold difference in oxalate values among 116 cultivars of soy, ranging from 82 to 285 mg/100 g dry weight [60]. Time of harvest can have additional impacts on oxalate concentrations [61]. Research has not demonstrated any differences in oxalate between organic and conventional cultivars [62]. Oxalate values in raw food items are not representative of actual content consumed, as items like legumes and greens are typically cooked prior to consumption. Traditional preparation methods have demonstrated efficacy in significantly reducing oxalate content. 

3.3. Effects of Cooking/Processing 

Like lectins, the cooking, preparation, and processing of food can impact the oxalate content and, therefore, mineral availability of food items (Table 2). Due to oxalate’s solubility in water, wet processing methods such as boiling, and steaming seem to be the most efficient solutions to decreasing oxalate content. Chai and Liebman reported significant reductions of soluble oxalate in vegetables by boiling for 12 min, ranging from 30 to 87% [54]. Spinach and Swiss chard experienced the largest losses (87 and 85%, respectively). Steaming has a lesser impact, though still resulted in losses of 46% and 42% in green Swiss chard and spinach, respectively [54]. Vegetables with lesser exposed surface area and relatively small amounts of oxalate, such as beets, carrots and Brussels sprouts, did not experience similar reductions in soluble oxalate [54]. These results are in agreement with a previous analysis on New Zealand vegetables [53]. Traditional and industrial cooking methods such as soaking overnight and boiling or autoclaving, significantly reduces total and soluble oxalate content in legumes. Cooking lentils on a hot plate for just fifteen minutes reduced soluble oxalate content by 42.6%, and in chickpeas (60 min) by 19.5% [58]. Common beans (cooked for 45 min) experienced a 59.61% loss in oxalate. Even further reductions of 85.7–92.9% were observed in canning (autoclaving) and microwaving of legumes [58]. It has also been found that an overnight soak, followed by a 2-h boil reduced soluble oxalate in red beans by 40.5% [58]. In contrast, there was a 76.9% loss of soluble oxalate in white beans [55]. These differences may be due to variations in genetics, growing conditions, cooking times and exact cooking temperatures. Roasting of peanuts, cashews and almonds did not have any significant impact on oxalate content [56]. In most cases, cooking techniques significantly reduces soluble oxalate, and should therefore enhance mineral availability. Aside from cooking, pairing high-oxalate foods with calcium-rich foods may offset soluble oxalate absorption. A normal calcium diet (800–1,000 mg/day) should be able to offset potential inhibitory effects from dietary oxalates [63]. 

3.4. Safety 

Despite evidence of relatively low soluble oxalate concentration in most ‘problematic foods’, dietary oxalate is thought to play a role in hyperoxaluria, a risk factor in the formation of calcium oxalate kidney stones (Table 1). Total dietary oxalate intake is only in the range of 50–200 mg, though in some individuals could be as high as 1000 mg [64]. It has been suggested that dietary oxalate may contribute up to 50% of total urinary oxalate excretion, and that one-third of stone formers hyper-absorb oxalate at a rate of more than 10% total oxalate consumed [65]. 

3.5. Human Studies 

A study of 20 healthy men and women found that an oxalate-rich diet (600 mg/day from rhubarb juice) significantly increased urinary excretion from 0.354 to 0.542 mmol/24 h [64]. However, oxalate is not typically consumed every day in such a concentrated form as rhubarb juice, but is, instead, a small fragment in an intricate web of dietary factors. Observing dietary patterns, a prospective analysis from the Nurses’ Health Study (NHS) found only a modest association between dietary oxalate and kidney stone formation after multivariate adjustment [66]. Participants in the highest quintile as compared to the lowest quintile of dietary oxalate, experienced a relative risk of 1.22 for men and 1.21 for older women. Even more significant, in men with lower calcium intake (<755 mg/day), the risk in the highest quintile of dietary oxalate jumped to 1.46. Conversely, in men with calcium intake at or above the median, the multivariate risk dropped to 0.83. Overall, authors concluded that dietary oxalate is not a major risk factor for stone formation [66]. In a more recent NHS I and NHS II analysis, authors again concluded that dietary oxalate had little impact on kidney stone formation, while dietary calcium intake was inversely associated with kidney stone formation [67]. Additionally, dietary potassium, magnesium, and phytate all decrease kidney stone formation through an array of mechanisms [68]. Despite significantly more dietary oxalates (254 mg/day) and oxalate-containing foods such as nuts, vegetables, and whole grains, participants with higher DASH scores have a 40–50% decreased risk of kidney stones [68]. This is perhaps attributed to the protective and synergistic effects of phytate, potassium, calcium, and other phytochemicals all abundant in the DASH dietary pattern. Similar findings regarding the protective role of vegetables on urolithiasis risk were reported by Zhuo et al. [69]. While animal protein consumption was associated with higher kidney stone risk, vegetable and tea consumption were associated with a decreased risk of stone formation. Tea is a rich source of oxalate, yet it is believed that polyphenols and other antioxidant phytochemicals may contribute to the prevention of stone formation [69]. Although there is a connection between calcium oxalate excretion, exogenous (dietary) oxalate, and stone risk, the association may be more complex than once believed. Gastrointestinal health may also play a role in oxalate absorption and associated health risks. Those with digestive disorders such as inflammatory bowel disease (IBD) have been shown to be at higher risk for calcium-oxalate kidney stones, assumed to be partially caused by oxalate hyperabsorption [70]. Patients with bowel disorders often experience deranged intestinal barrier function, characterized by increased intestinal permeability [70]. Fat malabsorption, secondary to epithelial damage, may also contribute to excess calcium-fatty acid salts, in turn increasing the availability of soluble oxalate [71]. The combination of these factors is theorized to increase oxalate absorption, however, the association between intestinal permeability and oxalate hyperabsorption has yet to be proven. Interestingly, children with autism have demonstrated increased plasma and urinary oxalate levels, but not increased risks of kidney stone formation [72]. This result may be partially explained by increased intestinal permeability and additional dysbiosis found in those with autism spectrum disorders, though is yet to be completely elucidated [73,74]. The gut microbiome, or oxalobiome, may also play a role in reducing dietary oxalates, as bacterial species like Oxalobacter formigenes possess oxalate-degrading genes [75]. Nonetheless, human trials using oxalate-degrading probiotics have been mixed, and for the most part, unsuccessful [76,77]. 

3.6. Conclusions 

Despite the demonization of oxalate and promotion of a low-oxalate diet in kidney stone patients, more recent observational studies of dietary patterns may prompt a reevaluation of current guidelines. Certain segments of the population do seem to be at greater risk of increased oxalate excretion, and consuming oxalate-rich foods may play a possible role in kidney stone formation, but other factors such as food preparation techniques, calcium intake, endogenous oxalate production, and intestinal health may play a larger role than once thought. Cooking oxalate-rich foods, as well as consuming adequate amounts of calcium and potassium demonstrate efficiency in significantly minimizing available soluble oxalate from dietary sources. Furthermore, oxalate containing foods possess an array of protective, beneficial compounds which may outweigh any possible negative effects of oxalate.