Calling for citrates? Further Evidence for this Extra Ketogenic Diet Supplement

Welcome to 2020!

For this issue of Keto News, I will profile a new article published in January in the journal Developmental Medicine and Child Neurology. This paper adds to the literature about the benefits of using citrates, oral supplements (either pills, crystals, or liquid), to make urine (and blood) less acidic.

The primary reason is to lower the risk of kidney stones. They may also reduce the chances of acidosis. Both of these can happen while on the ketogenic diet.

A Body of Evidence on the Benefits

Eleven years ago, in 2009, we published a paper in Pediatrics about the use of citrates in children on the ketogenic diet. We found that using Polycitra-K™ crystals at 2 meq/kg/day divided twice daily helped significantly reduce the chances of kidney stones in children on the ketogenic diet from 10.5% to 2.0%. When used in every child on the ketogenic diet automatically, the rate dropped to 0.9%. We profiled these results along with other efforts to prevent, not just treat side effects, in the August 2009 Keto News. Since that time, we now use citrates in every single child on the ketogenic diet (not the modified Atkins diet, however).

Not every ketogenic diet center agrees with this plan though. As mentioned in our 2019 ketogenic diet consensus statement, when surveyed only 14 of 25 centers (56%) use citrates automatically. Therefore, in the Table 5 of recommended supplements, citrates are listed as “optional” not “mandatory.”

New Research Strengthens Case for Citrate Use

This new paper from Bjorn Bjurulf from Norway and Tove Hallböök from Sweden adds further evidence on the value of using citrates in all ketogenic diet children. They looked at 29 children started on the ketogenic diet before 2007 (who did not receive citrates) and compared them to 22 children started after 2007 (who did based on the Pediatrics paper results).

What were the key findings?

• 0 of 22 who had Polycitra-K™ had acidosis in their blood versus 10 of 29 who did not receive Polycitra-K™. This was statistically significant.
• 0 of 22 who had Polycitra-K™ had kidney stones versus 2 of 29 who did not receive Polycitra-K. This was not statistically significant though.
• The average serum CO2 (measure of acidosis) was 20 mmol/L with citrates, versus 14 mmol/L without.
• There was no negative impact of citrates on either seizure control or blood levels of ketones.
• Children were able to get to higher ketogenic ratios more quickly with the use of citrates.

A commentary written by Natasha Schoeler and her team from England in the same issue commended the authors for the study but raised some questions.

• First, the children receiving citrates were younger (median age 1 year 7 months vs. 6 years 1 month). This could suggest younger children could be at lower risk, influencing the results.
• Additionally, the long-term benefits and risks were not studied. This research looked at only several months.
• I’ll also personally add that maybe other things could have changed at this ketogenic diet center after 2007 when citrates were used in all children (such as, giving more fluids, lower use of seizure drugs that could cause acidosis like topiramate or zonisamide, etc.).

What does this mean?

Regardless, this study adds to the evidence showing benefit for using citrates for all children on the ketogenic diet. At our hospital (Johns Hopkins), we have been doing this now since 2006.

More studies are needed to potentially change the eventual 2029 consensus statement to suggest all children should be on citrates.

• The authors hint that bone loss might be better if acidosis is less, and citrates could help that.
• We certainly need to know if this is just a problem for older children and those on certain antiseizure drugs, or if acidosis and kidney stones are a universal problem.
• Finally, there have been some issues over the years with United States pharmacies not stocking Polycitra-K™ or certain citrate brands. As a result, families might have issues with costs and availability.

References

Bjurulf B, Magnus P, Hallböök T, Strømme P. Potassium citrate and metabolic acidosis in children with epilepsy on the ketogenic diet: a prospective controlled study. Dev Med Child Neurol. 2020 Jan;62(1):57-61.

Schoeler NE. Potassium citrate supplementation with ketogenic dietary therapy for drug-resistant epilepsy. Dev Med Child Neurol. 2020 Jan;62(1):8.

Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Bergqvist AGC, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli Jr DR, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open 2018 May 21;3(2):175-192.

McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric Use of Potassium Citrate Reduces Kidney-Stone Incidence with the Ketogenic Diet. Pediatrics. 2009 Aug;124(2):e300-4.