A number of programs and tests focus on high oxalic acid, also called oxalate. In my program, the issue of high oxalate is integrated into my larger concern about overall biochemical balance. Aside from diet, there are a number of factors that may contribute to high oxalate levels. A determination if the trigger is, for example, high yeast or fungi, a lack of B12, or low ATP, is made through interpretation of testing. The reason for the high oxalate then guides your decisions as to how you address the problem. High oxalate may be due to yeast and fungal infestation. These factors can be investigated with a CSA test and GI Test, among others. Several chapters in this book contain suggestions for what to do when these issues are found.High oxalate can also be caused by low B12. Low B12 makes the Krebs cycle run in a reverse direction, which increases oxalate. Check cobalt levels on a UEE and HMT. Lithium transports B12 into your cells. Be sure that lithium is in balance with these two tests as well. The Krebs cycle is the energy/ATP generating portion of the mitochondria in your cells. Your level of B12 impacts enzymes in the Krebs cycle, and the levels of Krebs intermediates are affected. Adequate levels of B12 increase fumarate reductase, which then aids in processing oxalate and fumarate (Kurumada and Labbe Science Vol 151 page 1228).Conversely, lack of B12 leads to increases in citrate lyase and succinate dehydrogenase (Frenkel et al JBC Vol 251 page 2147). The net effect of these enzymatic changes is to increase oxalate and fumarate levels. While fumarate is generally converted to malate, it may happen that when fumarate levels are high enough, some of it is converted to tartarate. Feedback inhibition by high oxalate in addition to high fumarate may control the flow into malate, such that fumarate and oxalate are converted to tartarate. The pathway that leads to formation of tartarate from oxalate has been defined (Nakamura and Ogata, JBC Vol 248 page528 and Shreeve and Meuter JBC Vol 239 page 729), as has as the path from fumarate to tartarate (Kuni and Hernandez JBC page 201 and Finkle JBC page 349).Conditions of B12 deficiency, coming either as a result of mutations in the methylation cycle, and/or by high level depletion of B12 through endurance training or sports, can lead to increased levels of tartarate, fumarate, and oxalate. High levels of tartarate in the absence of high arabinose, or high levels of fumarate, should lead you to consider supplementing with multiple forms and routes of B12. This includes chewable hydroxyl, adenosyl, and methyl B12. The relative amounts depend on your Nutrigenomics.

If you have high oxalate levels, you should consider increasing your B12 support for an additional reason. Relative B12 deficiency increases the conversion of citrate to oxalate via citrate lyase. Consider Lactoferrin, Vitamin K, Pantothenic Acid, Riboflavin-5-Phosphate, Curcumin, Benfotiamine, and GSH to increase the flow from pyruvate through citrate and onto isocitrate as another way to decrease high oxalate. The use of MitoForce may also support this conversion.

High leucine in the absence of high valine or isoleucine can occur secondary to low phosphate. This can also cause increases in oxalate, so check to determine if leucine is high on a UAA. If so, consider ATP and Riboflavin-5-Phosphate to support phosphate.

High oxalate may also be due to excess glycine secondary to SHMT + or excess iron. Glycine can be checked on a UAA, and iron levels are on a UEE and HMT. As discussed in the UAA chapter, high glycine can be addressed with supports for SHMT.

If threonine is high on a UAA test, this may be an indication of high oxalic acid.

High levels of oxalates may increase ACE activity. The use of anxiety support and progesterone may be helpful. (Umekawa et al J. Am Soc Nephrol Vol 15, 2004).

High levels of citrate or high levels of the intermediates that precede acetyl CoA on the MAP diagram, i.e., pyruvate, lactate, etc., may be an indirect indication of high oxalate, as the cycle is not incorporating at 11:00 (oxalate) well enough to be moving around to 1:00 (citrate) properly.

Also, a build up at 1:00 (citrate) may be causing a backup in the cycle, which may be an indirect indication of high oxalate. Consider MitoForce or Lactoferrin, Vitamin K, Riboflavin-5-Phosphate, Pantothenic Acid, and Benfotiamine to get the portion of the cycle from 11:00 to 1:00 moving.

Those who are ACAT + may also have problems converting nutrients from food into the Krebs energy cycle, and the use of ACAT/BHMT capsules may be a help in this regard.

Research articles illustrate a relationship between B12 and ATP which seems to present a catch 22. ATP, the fuel generated by your body to drive its biochemical reactions, is created by your Krebs energy cycle. The Krebs cycle needs B12 in order to function optimally. If your Krebs cycle is not functioning optimally, ATP production is reduced. Yet, ATP is needed to transport B12 into your cells. However, lithium also plays a role in B12 transport, so lithium levels should be checked and supported as needed. MitoForce or ATP, NADH, Vitamin E succinate, and Malic Acid also play a role in B12 transport and may be supplemented as needed.

High levels of sulfur in your system can have a negative impact on the regeneration of ATP and NADH. This may be a particular issue for those who are SUOX + – or CBS ++. MitoForce or ATP, NADH, Vitamin E succinate, and Malic Acid help to regenerate these important intermediates also.

The supplements suggested for consideration to reduce high oxalate depend upon its cause. If low B12 is the issue, consider a source of low dose lithium, such as All in One and/or BeCalm Spray, in addition to B12 itself.

If high glycine and/or high iron are the issues, consider SHMT support.

If leucine alone is elevated on a UAA, without concurrent increases in isoleucine and valine, then consider ATP and Riboflavin-5-Phosphate .

Aluminum and thallium can impair the function of the Krebs cycle, so address thallium and aluminum if they are found to be elevated on HMT, UTM or FMT.

Rule out yeast and fungal issues on a CSA test and GI Test.

High FIGLU suggests that adequate folate is not in place. All in One supplies low doses of folic acid, folinic acid, and 5 methyl THF. There are two key reasons to support with low doses of folate/folic acid, in addition to the use of specific types of folate such as 5 methyl THF that help to bypass mutations like MTHFR C677T. First, since 1959 it has been known that “folic acid deficiency results in inability to degrade formiminoglutamic acid (FIGLU) to glutamic acid, so that FIGLU accumulates in excessive amounts and is excreted in the urine”. (Luhby, Am J Clin Nutr). FILGU levels are measured on this MAP test, and high levels suggest a need to use low dose folate/folic acid support. The second reason to look at low dose folic acid/folate is the pathway that involves MTHFS. A low dose form of plain folate or folic acid is supplemented in part to address possible MTHFS mutations, especially since they are not generally identified on most nutrigenomic tests. MTHFS is another enzyme in the methylation pathway. It functions at 11:00 in the folate cycle, between 5 formyl THF (folinic) on the way to produce tetrahydrofolate at 12:00. MTHFS functions to address SHMT and the formation of the purines guanine and adenine for DNA and RNA formation. If there is a mutation that impacts the ability of MTHFS to function, it can increase folinic acid to high levels and limit the synthesis of purines, as well as decrease the THF level. In this program, my policy is to use only low dose folinic acid, to add nucleotides to support DNA and RNA production, and to use low dose folic acid along with probiotics as a secondary way to make THF. In this way, I bypass the impact of any possible MTHFS mutation, even if I do not have nutrigenomic data regarding this gene. This again highlights why I want to think about all aspects of the pathway when adding support. I choose to add only low dose folinic acid to help keep SHMT in balance without allowing the levels of folinic to climb, which might happen if you are adding high dose folinic and have a MTHFS mutation. I add nucleotides to supply purines and pyrimidines in case the pathway for their formation is not fully functional. I add low dose folic acid to have a secondary route for making THF that consumes excess glutamate in doing this. The rationale behind also adding low dose 5 methyl THF is that the way to bypass an MTHFR C677T mutation is with 5 methyl THF. If you look at the biochemical diagrams you can see this. No amount of folinic, folate, or folic acid is going to bypass a MTHFR C677T mutation. So, the whole conversation about folic acid or folate is actually misplaced, as the real issue is 5 methyl THF. There is some sort of misconception out there that folate will bypass MTHFR. To be clear, 5 methyl THF is the only way to bypass MTHFR C677T. I have it in low dose form in both All in One as well as Methylmate B. If you are C677T ++, using high dose 5 methyl THF can trigger more detox than you can handle, especially if you are an adult. This is why All in One uses low dose 5 methyl THF, and my stand alone source of 5 methyl THF, Methylmate B, is a liquid, so you have exquisite control over increasing or decreasing its dose. MOST of the folate that is used for this program is 5 methyl THF, with some low dose folinic acid. Folinic is useful for those who are SHMT + or have iron levels that may increase SHMT activity. Some low dose folic acid/folate is helpful for other aspects of the pathway, and that is why some very, very low dose folic acid is included in the formulation.To summarize, I do feel that some low dose folinic acid is needed to help to control SHMT, which is why All in One also has some low dose folinic. I do not like high dose folinic as those with MTHFS mutations can have a problem with it. Finally, for adequate processing of FIGLU, I want some low dose folate/folic acid in your system. Because the various forms of folate compete with each other for transport into your cells, the ratio in the All in One is mostly 5 methylTHF, with a lesser amount of folinic, and finally the least amount of folic acid.Now I am going to be very specific with regard to why I use low dose folic acid rather than folate. Folate is basically a chain of glutamates. The difference between folic acid and folate is the stability and the length of their glutamate chains. So, if you are MTHFR C677T++ and you take high dose folate, you potentially have a chain of unused glutamate molecules left in your system. You cannot process it efficiently to 5 methyl THF because of your SNPs. You run the risk of folate breaking down to release glutamate into your system. STEP 1 of this program is focused on glutamate/GABA balance. I have made significant progress for some individuals merely by getting their glutamate and GABA into balance. Thus, I am not choosing to add high doses of a form of folate that could break down into glutamate, especially in the population I work with.

One of the main differences between folic acid and folate is that folic acid has a shorter glutamate chain than folate. Folic acid is also more stable, so it is less likely to break down into glutamate. I am using only a tiny bit of folic acid, to allow FIGLU to convert to glutamic acid. I am not using high dose folic acid, as that is not going to bypass MTHFR in any event. I understand there are other programs out there that use higher doses of plain folate. Perhaps those programs are less concerned with the glutamate issue.

I have specific reasons for the choices I make in terms of supplements and the forms that I use. Natural folate has more glutamate residues and can break down more easily to release those glutamate molecules into your system, so I prefer to use a VERY low dose of folic acid. There are only approximately 15 micrograms of folic acid in All in One and about 25 micrograms in Ultimate B. This program uses some very, very low dose folic acid for the reactions that need it, but the focus is more heavily on the use of 5 methyl THF and low dose folinic acid.

The use of LOW dose folic acid is a choice, to limit the risk of increased glutamate in your system. The RDA for folate/folic acid is 300 micrograms for a child that is 1 year old, up to 1,000 micrograms daily for an individual 19 years of age or older. Thus the 15 to 40 micrograms used for this program is not an issue, especially since the body does need some folate/folic acid aside from the need for 5 methyl THF and folinic. To put this in an easily understandable perspective, a bowl of cheerios has 400 micrograms of folic acid, as compared to the 15 to 40 micrograms used in this program.

In addition to making rational choices in terms of folic acid versus folate, and only using low dose folinic out of consideration for possible MTHFS mutations, I am already taking into account the need to balance the production of purines, thymidine levels, controlling SHMT, and producing methionine from homocysteine with the supplementation I have in place for the methylation cycle.

To reiterate the approach: (1) get the BHMT pathway moving with Phosphatidyl Serine Complex (PS/PE/PC) plus DHA, SAM-e if tolerated, All in One, Ultimate B, and low dose methylation RNA; (2) add some low dose lithium support with BeCalm Spray, and run a HMT to be sure you have checked lithium to see if you need low dose Lithium Orotate. If aggression is an issue, pay close attention to potassium and rubidium on your HMT. If your lithium is very low, run a HMT every 3 to 4 months to keep an eye on levels; (3) once lithium is in balance, you can add extra B12; (4) add Methylmate A and Methylmate B to be sure you have the cycle fully supported; (5) if you have SHMT + status or high iron on HMT and UEE, use SHMT support along with step 1 and 2 above; (6) be sure you have probiotics in place, focusing on Lactobacillus and Bifidobacter; (7) run a HMT to check lithium every few months once you have extra B12 in place.

High levels of the enzyme urocanase will also increase FIGLU. Urocanase is produced by certain bacteria, including Pseudomonas, so consider a CSA test and GI Test when high FIGLU is noted on a MAP.

Urocanase is limited by succinate. Be sure that succinate levels on a MAP test are in balance, because a lack of succinate combined with bacterial increases in urocanase can be factors in high FIGLU in addition to a need for folate.

In terms of support for high levels of FIGLU, the use of All in One supplies specialized forms of folate. Also, once it is clear that lithium is in balance on a HMT, consider low dose Methylmate A and Methylmate B for comprehensive methylation support. Use Vitamin E succinate if succinate levels are low. Also, consider a CSA test and GI Test to rule out Pseudomonas. Consider the use of gut herbs including Naturomycin Spray, Naturomycin capsules, and grapefruit seed extract (GSE capsules or GSE liquid) when necessary.