I find the Thiamine deficiency link to oxalate to be very interesting. I take 450mg of Benfotiamine (fat soluble form of Thiamine) every day. Susan has questioned my high vitamin C intake because C can produce high blood oxalates. Yet my high daily intact seems to to grossly impact me in a negative way with regards leg cramping, etc. So I am wondering if perhaps Thiamine is helping to moderate or eliminate blood oxalates from Vitamin C metabolism.
After reading an interesting article on DCA (dichloroacetate), a nonpatentable substance that's apparently been in use for some 30 years for treating mitochondrial disorders and is now showing some promising results in the world of cancer research, I came across something that you - particularly Susan - might find interesting.
From what I can gather one of the negative side effects of using DCA is that it is converted to glyoxalate which is then converted to oxalate when thiamine is deficient. So I'm wondering how much of a role thiamine plays in reducing the oxalate load.
Susan - have you investigated this relationship between thiamine deficiency and oxalates? I've put an abstract below. I've just come across this info so I can't say I've looked into it very much, but enough to think that there may be something worth looking into here.
Those who are interested in what's happening with DCA and cancer might want to start here:
You can also google for dca + cancer for some interesting articles as well.
Chronic toxicity of dichloroacetate: possible relation to thiamine deficiency in rats.
Stacpoole PW, Harwood HJ Jr, Cameron DF, Curry SH, Samuelson DA, Cornwell PE, Sauberlich HE.
Department of Medicine (Division of Endocrinology and Metabolism), University of Florida, College of Medicine, Gainesville 32610.
The chronic use of dichloroacetate (DCA) for diabetes mellitus or hyperlipoproteinemias has been compromised by neurologic and other forms of toxicity. DCA is metabolized to glyoxylate, which is converted to oxalate and, in the presence of adequate thiamine levels, to other metabolites. DCA stimulates the thiamine-dependent enzymes pyruvate dehydrogenase and alpha-ketoacid dehydrogenase. We postulated that the neurotoxicity from chronic DCA administration could result from depletion of body thiamine stores and abnormal metabolism of oxalate, a known neurotoxin. For 7 weeks, rats were fed ad lib. Purina chow and water or chow plus sodium DCA (50 mg/kg or 1.1 g/kg) in water. A portion of the DCA-treated animals also received intraperitoneal injections of 600 micrograms thiamine three times weekly or 600 micrograms thiamine daily by mouth. Thiamine status was assessed by determining red cell transketolase activity and, in a blinded manner, by recording the development of clinical signs known to be associated with thiamine deficiency. At the 50 mg/kg dose, chronic administration of DCA showed no clinical toxicity or effect on transketolase activity. At the 1.1 g/kg dose, however, DCA markedly increased the frequency and severity of toxicity and decreased transketolase activity 25%, compared to controls. Coadministration of thiamine substantially reduced evidence of thiamine deficiency and normalized transketolase activity. Inhibition of transketolase by DCA in vivo was not due to a direct action on the enzyme, however, since DCA, glyoxylate, or oxalate had no appreciable effects on transketolase activity in vitro. After 7 weeks, plasma DCA concentrations were similar in rats receiving DCA alone or DCA plus thiamine, while urinary oxalate was 86% above control in DCA-treated rats but only 28% above control in DCA plus thiamine-treated animals. No light microscopic changes were seen in peripheral nerve, lens, testis, or kidney morphology in either DCA-treated group, nor was there disruption of normal sperm production in the DCA-treated group. We conclude that stimulation by DCA of thiamine-requiring enzymes may lead to depletion of total body thiamine stores and to both a fall in transketolase activity and an increase in oxalate accumulation in vivo. DCA neurotoxicity may thus be due, at least in part, to thiamine deficiency and may be preventable with thiamine treatment.
PMID: 2318357 [PubMed - indexed for MEDLINE]
1: Ann Nutr Metab. 1987;31(6):354-61.
Oxalate metabolism in thiamine-deficient rats.
Sidhu H, Gupta R, Thind SK, Nath R.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Male weanling rats were maintained on a thiamine-deficient diet for 4 weeks, and compared with ad libitum and pair-fed controls. Thiamine deficiency led to slow growth and finally a decrease in body weight. Liver and kidney weights of the deficient rats were low, but appropriate to the body weight. Thiamine deficiency also caused a significant decrease in erythrocyte transketolase levels. The decarboxylation of glyoxylate both via the glyoxylate oxidation cycle and alpha-ketoglutarate:glyoxylate (alpha-KG:GA) carboligase was significantly lower in the liver and kidney mitochondria, leading to accumulation of glyoxylate in the tissues and its excretion in the urine. Part of the accumulated glyoxylate is converted to oxalate, causing hyperoxaluria.
PMID: 3426152 [PubMed - indexed for MEDLINE]
1: Biochem Int. 1986 Jan;12(1):71-9.
Absorption of glyoxylate and oxalate in thiamine and pyridoxine deficient rat intestine.
Sidhu H, Gupta R, Farooqui S, Thind SK, Nath R.
Dietary deficiency of thiamine or pyridoxine has been shown to produce hyperoxaluria and renal stone formation in man and experimental animals. To determine the possible contribution of exogenous glyoxylate and oxalate, the intestinal transport of [14C] - oxalate and [14C] - glyoxylate was measured in vitamin B1 and B6 deficient rats and their respective pair-fed controls. Results indicate that glyoxylate and oxalate are passively diffused from lumen to lamina propria in thiamine deficient and their pair-fed controls with no significant change in the rate of uptake of both the substrates. However B6 deficient rats showed a significant enhancement in the rate of oxalate uptake due to development of a new biphasic transport system. The rate of glyoxylate uptake by simple passive diffusion remained unaltered in pyridoxine deficiency.
PMID: 3947375 [PubMed - indexed for MEDLINE]