Bone broth, also known as stock, is recently back in fashion with many purported health benefits. I will admit my own bias in being rather a fan of some good bone broth and suspect it is a beneficial component of the diet, although good research is currently still rather lacking.
However, it is important not to idolise particular foods, as almost all foods have some potential downsides. Therefore, I was interested to find a potential downside to bone broth in the link between broth, gelatine, oxalate, and kidney stones. This may seem unlikely as bone broth does not contain any oxalate, but bear with me as this first requires a diversion into the formation of kidney stones and where oxalate comes from.
Kidney stones
Kidney stones are really quite common, affecting about 1 in 10 people at some point in their lives. Most (~90%) kidney stones are formed of crystals of calcium and oxalate. Crystals of calcium oxalate begin to form when the concentration of calcium and oxalate reaches a high enough concentration. This means that a higher concentration of oxalate in the kidneys is a risk factor for developing kidney stones. As oxalic acid is found in a variety of foods, patients with recurrent kidney stones are often advised to limit their intake of foods containing a lot of oxalate. However, the oxalate from food only makes up a proportion of the oxalic acid in excreted from by the kidney, with estimates of between 24% and 53% originating from the diet (Holmes 2001).
Hydroxyproline metabolism
The rest of the oxalate passing through the kidneys is produced by the body itself. Oxalate is the final step in the breakdown of a common amino acid called hydroxyproline. Collagen is the major structural protein in the body and also the most abundant protein making up from 25% to 35% of all the protein in the body. Mostly found in fibrous tissues such as tendons, ligaments, and skin. It is also abundant in corneas, cartilage, bones, blood vessels, the gut, spinal discs, and the dentin in the teeth. Normally, the collagen in our connective tissues turns over at a very slow and controlled rate and is always slowly being broken down and rebuilt. This constant renewal of collagen requires the body to remove excess amino acids released during the process.
The metabolic pathways of hydroxyproline metabolism into oxalate. Source: (Knight 2006).
The daily turnover of collagen from your own body is a major source of hydroxyproline. Just turning over your own collagen accounts for 5-20% of the urinary oxalate daily (Knight 2006). Excess hydroxyproline goes through a complex metabolic pathway in the liver. The majority of the hydroxyproline in this pathway is actually converted into another amino acid, glycine, and used for other purposes. There remainder is finally converted to oxalic acid and glycolate, which are excreted by the kidneys.
Bone broth gelatine contains hydroxyproline
“Amino Acid Composition in Gelatine chart” by Hugahoody
We now return to bone broth of which hydrolysed collagen, better known as gelatine, is the main protein. It is gelatine that makes a good broth gel when cooled and contains the particular composition of amino acids that are currently making broth a popular health food. You can see from the pie chart below that hydroxyproline (Hyp) makes up 12% of the amino acids in gelatine. After eating broth or gelatine the body suddenly has a lot of hydroxyproline to deal with and a proportion of this is converted into oxalate.
A ten gram dose of gelatine increases hydroxyproline in the blood
Change in blood hydroxyproline (Hyp) (inset), glycolate (■), and oxalate (–▲–) after ingestion of 10 g of gelatine. Source: (Knight 2006).
When gelatine is consumed there is a rise in the amount of hydroxyproline in the blood for several hours. In a fascinating paper from 2007, John Knight and his colleagues fed ten subjects thirty grams of supplemental gelatine and then measured their blood and urine. From their graph below you can see that the hydroxyproline (Hyp) levels rapidly rose in the blood and remained up to four times higher for several hours. However, oxalate levels in the blood are more tightly controlled and did not rise.
A ten gram dose of gelatine increases oxalate in the urine
Amount of glycolate (■) and oxalate (–▲–) in the urine following ingestion of 10 grams of gelatine. Source: (Knight 2006).
In comparison, the amount of oxalate in the urine increased for at least eight hours after consuming the gelatine. Oxalate concentration in the urine reached nearly five times higher a few hours after ingesting gelatine. This is due to the kidneys clearing oxalate out of the body as fast as it is being produced. This ten gram dose of gelatine would contain about a gram of hydroxyproline.
Lower doses of gelatine also increase oxalate in the urine
Increases in urinary oxalate (■) and glycolate (□) excretion over fasting levels in a 6 hour period following ingestion of various amounts of gelatine. Source: (Knight 2006).
This is all very well you may say, but ten grams of gelatine is rather more than most people consume in one go. Well, the authors quite rightly followed this up with a range of doses of gelatine more commonly found in the diet. You can see from the graph below that one and two gram doses had little impact on the amount of hydroxyproline. Between five and ten grams of gelatine, there was a significant increase in both hydroxyproline in the blood and oxalate in the urine. Interestingly, 12 grams is the serving of gelatine recommended by a popular geleatine supplement company, just to give perspective on the amounts involved.
Relevance
It would be appropriate now to ask how relevant this information is. There is certainly no study on people who consume bone broth or gelatine regularly and their risk of kidney stones. There is some epidemiological evidence that suggests it may be relevant. This comes from studies comparing meat intake and vegetarians. A recent study has found an association between meat intake and kidney stones, with a significantly reduced risk of stones occurring in vegetarians or people eating less meat (Turney 2014). The hydroxyproline content of meat products is suspected to play a role in this increased risk. Meat is the main source of gelatine in most peoples’ diets and a hundred grams of beef can contain a few grams of collagen. Of course, this cannot be treated as conclusive evidence as it is only an association. In an older study, meat intake – which contains collagen and hydroxyproline – was linked to increasing oxalate excretion, but only in a subgroup of men with unexplained recurrent kidney stones (Nguyen 2001).
Implications
The research presented here is not a intended to scare people away from bone broth, stock, gelatine, or meat. Most people never get kidney stones and even for those who do, there are a number of factors that influence stone development. However, it is a potential factor that may be important for some people to know. As is it not commonly discussed, some people may not make a connection between broth or gelatine intake and kidney stones. If you need to reduce your oxalate levels, caution may be needed when taking extra gelatine or bone broth.
References
Holmes RP, Goodman HO, Assimos DG. (2001) Contribution of dietary oxalate to urinary oxalate excretion. Kidney International. 59(1):270-6.
http://www.ncbi.nlm.nih.gov/pubmed/11135080
“BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable.
METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections.
RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%.
CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.”
Knight J, Jiang J, Assimos DG, and Holmes RP. (2006) Hydroxyproline ingestion and urinary oxalate and glycolate excretion Kidney International. 70(11): 1929–1934.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268952/
“Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20−50% of glycolate excreted in urine and 5−20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration.”
Turney BW, Appleby PN, Reynard JM, Noble JG, Key TJ, Allen NE.(2014) Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).European Journal of Epidemiology. 29(5):363-9.
http://www.ncbi.nlm.nih.gov/pubmed/24752465
“The lifetime prevalence of kidney stones is around 10 % and incidence rates are increasing. Diet may be an important determinant of kidney stone development. Our objective was to investigate the association between diet and kidney stone risk in a population with a wide range of diets. This association was examined among 51,336 participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from Hospital Episode Statistics in England and Scottish Morbidity Records. In the cohort, 303 participants attended hospital with a new kidney stone episode. Cox proportional hazards regression was performed to calculate hazard ratios (HR) and their 95 % confidence intervals (95 % CI). Compared to those with high intake of meat (>100 g/day), the HR estimates for moderate meat-eaters (50-99 g/day), low meat-eaters (<50 g/day), fish-eaters and vegetarians were 0.80 (95 % CI 0.57-1.11), 0.52 (95 % CI 0.35-0.8), 0.73 (95 % CI 0.48-1.11) and 0.69 (95 % CI 0.48-0.98), respectively. High intakes of fresh fruit, fibre from wholegrain cereals and magnesium were also associated with a lower risk of kidney stone formation. A high intake of zinc was associated with a higher risk. In conclusion, vegetarians have a lower risk of developing kidney stones compared with those who eat a high meat diet. This information may be important to advise the public about prevention of kidney stone formation.”
Nguyen QV, Kälin A, Drouve U, Casez JP, Jaeger P. (2001) Sensitivity to meat protein intake and hyperoxaluria in idiopathic calcium stone formers. Kidney International. 59(6):2273-81.
http://www.ncbi.nlm.nih.gov/pubmed/11380831
“BACKGROUND: High protein intake is an accepted risk factor for renal stone disease. Whether meat protein intake affects oxaluria, however, remains controversial in healthy subjects and in stone formers. This study was designed (1) to test the oxaluric response to a meat protein load in male recurrent idiopathic calcium stone formers (ICSFs) with and without mild metabolic hyperoxaluria (MMH and non-MMH, respectively), as well as in healthy controls, and (2) to seek for possible disturbed vitamin B(6) metabolism in MMH, in analogy with primary hyperoxaluria.
METHODS: Twelve MMH, 8 non-MMH, and 13 healthy males were studied after five days on a high meat protein diet (HPD; 700 gmeat/fish daily) following a run-in phase of five days on a moderate protein diet (MPD; 160 g meat/fish daily). In both diets, oxalate-rich nutrients were avoided, as well as sweeteners and vitamin C-containing medicines. Twenty-four-hour urinary excretion of oxalate was measured on the last day of each period, along with 4-pyridoxic acid (U(4PA)) and markers of protein intake, that is, urea, phosphate, uric acid, and sulfate. Serum pyridoxal 5′ phosphate (S(P5P)) was measured after protein loading.
RESULTS: Switching from MPD (0.97 +/- 0.18 g protein/kg/day) to HPD (2.26 +/- 0.38 g protein/kg/day) led to the expected rise in the urinary excretion rates of all markers of protein intake in all subjects. Concurrently, the mean urinary excretion of oxalate increased in ICSFs taken as a whole (+73 +/- 134 micromol/24 h, P = 0.024) as well as in the MMH subgroup (+100 +/- 144 micromol/24 h, P = 0.034) but not in controls (-17 +/- 63 micromol/24 h). In seven ICSFs (4 MMH and 3 non-MMH) but in none of the healthy controls (P = 0.016, chi square), an increment in oxaluria was observed and considered as significant based on the intra-assay coefficient of variation at our laboratory (8.5%). There was no difference in S(P5P)nd U(4PA)etween the groups after protein loading.
CONCLUSION: Approximately one third of ICSFs with or without so-called MMH are sensitive to meat protein in terms of oxalate excretion, as opposed to healthy subjects. Mechanisms underlying this sensitivity to meat protein remain to be elucidated and do not seem to involve vitamin B(6) deficiency.”
