Uric acid, calcification and low vitamin K2

*I added a little of my K2 powder to my Cheerful Juice mix - the dicalcium phosphate is anticaking agent, but I didn't use much, ~ 1 gram per day ~ 10 mg K2 and a couple 100 mg each of Ca & Ph.

What is Uric Acid? a metabolite of purine breakdown - high folate foods add to the body load of purine breakdown (green peas, asparagus, folic acid or folate supplements or fortified foods). High dose niacin use would also add to uric acid load, or high dose vitamin C. Hyperurecemia - elevated uric acid in the blood is a common cause of toe pain — called ‘gout’. (George, et al., 2023) Use of spleenwort fern in tea may help reduce uric acid levels. It is a diuretic, increasing urination, so have earlier in the day along with extra water. Tip via Nattering Naybob, this post.

Addition - the vitamin K2 series:

1. Post one on K2 - https://denutrients.substack.com/p/vitamin-k2-soft-tissue-calcification?r=os7nw

2. Post two on K2 - https://denutrients.substack.com/p/update-on-vitamin-k2-and-anticoagulant?r=os7nw

3. Addendum because I didn't read the fine print on the filler in a product post 3 on K2 - https://denutrients.substack.com/p/bulk-k2-addendum?r=os7nw

• My Cheerful Juice recipe is in this other post. DMG, dimethylglycine - can be calming and help sleep and I need it due to a gene difference. Bone broth would be a good source of glycine.

Elevated levels of uric acid is strongly associated with abdominal aortic calcification that it has been suggested for use as a biomarker, a lab screening test to look at for risk of vascular calcification. (Li and Chen, 2020) Use of certain diuretics or other medications may increase accumulation of uric acid and gene differences in the methylation cycle that tend to cause increased homocysteine can also be a risk factor or other gene alleles may be involved. There is a positive association between elevated homocysteine and elevated uric acid but not clear why… Brave AI summary. Brave AI reached the answer, or part of it, summary, with a revised prompt. Methylation cycle function affects purines through folate levels and that can lead to an increase in uric acid. Homocysteine can be elevated from certain methylation cycle dysfunctions, so the two issues would be positively associated due to both being affected by methylation cycle dysfunction.

“Correlation is not causation,” became pushed in the last few decades, I think as part of the canceling of parents of the vaccine injured children exhibiting sudden onset autistic changes or other injuries. Correlation does imply causation, but there might not be a directly causal link. Another factor might be affecting both things so that both things seem related but they may not have caused the other to happen. Crime rate increases in the summer and ice cream eating increases in the summer, so does that mean that criminals eat a lot of ice cream and then move away in the winter? Or does warmer weather lead to more crime in general, and more ice creaming eating by criminals or non-criminals, in general?

“Uric acid is the ultimate catabolite of purine metabolism in humans and higher primates. It is a weak organic acid that under physiologic conditions exists mainly as a monosodium salt. At a pH less than 5.75, as may occur in the urine, the predominant form is nonionized uric acid. The solubility of monosodium urate is about 18 times greater than uric acid in aqueous solutions. This solubility differential provides the therapeutic rationale for alkalinization of the urine pH to greater than 6.0 in patients forming uric acid stones.” (Barr, 1990)

A low blood level of uric acid is also a health risk and is commonly seen in Alzheimer’s dementia.

“Low uric acid, or hypouricemia, gets less attention because it affects far fewer people — only about 0.5% of the population. Yet it’s associated with serious neurologic disorders, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS), reduced kidney function and a painful nerve condition called trigeminal neuralgia. Higher uric acid is known to help protect against these disorders. Low uric acid is also associated with kidney damage after vigorous exercise (called exercise-induced kidney injury) and uric acid kidney stones.” […]

“Higher-than-normal uric acid can result from:

• Not excreting enough uric acid from the body, sometimes from dehydration but more often kidney disease.

• Drinking alcohol, which increases the risk of gout and gout flares.

• Eating a high-purine diet that includes a lot of red meat, shellfish, sweets, sugary sodas and high-fructose corn syrup. (Fructose from fruit can also contribute to high uric acid.)

• Obesity.

• Diabetes.

• Certain medications, including some used for arthritis, such as cyclosporine (Neoral) and tacrolimus (Prograf).

Low uric acid can be due to:

• Rare inherited disorders that decrease uric acid production.

• Fanconi syndrome, which causes the filtering tubes in your kidneys to excrete too much uric acid and other substances.

• Diabetes.

• Anti-gout drugs such as allopurinol (Zyloprim).

• Pregnancy.

• Malnutrition.

• A family history of hypouricemia.” - ‘High & Low Uric Acid Symptoms: How to Stay in a Safe Range,’ (arthritis.org)

It is important to note that uric acid containing kidney stones might result from either high or low uric acid levels, so automatically treating with allopurinol might make the stones worse if uric acid levels drop too much or were low to begin with. Kidney stones may not be diagnosed quickly because the main symptom is low back pain - in the area of the kidneys. (arthritis.org)

An inhibitor of the enzyme involved in purine metabolism is a typical treatment, but reducing purine intake (sardines are a very rich source) can help without inhibiting major enzyme pathways.

“Most patients with hyperuricemia are asymptomatic, and the diagnosis requires a high degree of suspicion as serum uric acid levels are no longer routinely measured on serum blood panels. Patients with hyperuricemia who develop gout are usually best treated with a xanthine oxidase inhibitor like allopurinol. Depending on the urinary chemistry and stone type, allopurinol, potassium citrate, or both may be recommended in nephrolithiasis.” (George, et al., 2023)

Risk factors for elevated blood uric acid include increased intake of uric acid precursors, reduced excretion, and/or increased retention due to medications.

“Etiology”

Uric Acid Overproduction

• Purine-rich diet: alcohol (especially beer); bacon; beef; lamb; turkey; veal; venison; organ meats; and certain fish and shellfish (anchovies, cod, tuna, sardines, herring, mussels, shrimp, lobster, codfish, scallops, trout, and haddock)

• Fructose causes hyperuricemia as its hepatic metabolism through the aldolase reductase pathway produces uric acid. High-fructose corn syrup and full-sugar sodas are especially harmful and are associated with obesity in children and adolescents. [7][8]

• Errors of purine metabolism: hypoxanthine-guanine phosphoribosyltransferase (HPRT or HGPRT) deficiency, phosphoribosylpyrophosphate (PRPP) synthetase overactivity.

• High cell breakdown or turnover: lymphoproliferative diseases, myeloproliferative disease, polycythemia vera, Paget disease, psoriasis, tumor lysis, hemolysis, rhabdomyolysis, extreme exercise, chemotherapy.

Decreased Uric Acid Excretion

• Acute or chronic kidney disease, acidosis (eg, lactic acidosis, ketoacidosis), hypovolemia, medication/toxins (diuretics, niacin, pyrazinamide, ethambutol, cyclosporine, beryllium, salicylates, lead, alcohol), sarcoidosis, hyperparathyroidism, hypothyroidism, Bartter syndrome, Down syndrome.[9]

Diuretic-induced Hyperuricemia

• Thiazide and loop diuretics tend to cause a dose-dependent type of hyperuricemia and possibly even gout.[10][11][12] They tend to increase renal uric acid reabsorption either directly or indirectly through volume depletion.[10][12][13][14]

• The net increase in relative risk of gout by diuretics is almost 80%.[15]

• An alternate or concurrent antihypertensive, including an angiotensin II receptor blocker (especially losartan) or an angiotensin-converting enzyme inhibitor, is recommended in patients with gout flares.[16][17][18][19][20][21][22]

• Most patients with diuretic-induced gout are treated with a xanthine oxidase inhibitor, such as allopurinol. However, if the patient is asymptomatic, no treatment is needed.” (George, et al., 2023)

Folate food sources

Folate is important for health, but if we aren’t processing it properly, then too much might lead to elevated uric acid.

• Legumes: Including beans, lentils, and peas. For example, one cup of cooked kidney beans contains about 131 mcg of folate, which is approximately 33% of the Daily Value (DV).

• Leafy Greens: Such as spinach, kale, collard greens, turnip greens, and romaine lettuce. These are excellent sources of folate.

• Citrus Fruits: Including oranges, lemons, and limes. Citrus fruits are particularly high in folate.

• Fortified Grains: Look for the term “enriched” on food labels for products like breads, cereals, pasta, rice, and wheat germ.

• Sweet Potatoes: Known for their high folate content.

• Asparagus: Eating just one cup of boiled asparagus provides about 65% of your daily folate needs.

• Brussels Sprouts and Broccoli: Both are rich in folate. *Leeks and green onions too I think. Each 100 grams of fresh leek stalks provide 64 micrograms of folate, which is 16% of the daily recommended intake (RDI); and 47 micrograms vitamin K (59 percent DV). (draxe.com)

• Soybeans: A good source of folate.

• Eggs: Provide a natural source of folate.

• (Brave AI, various links included)

(Grok AI, on x.com) Elevated uric acid (hyperuricemia) has been associated with vascular calcification, particularly in the context of cardiovascular disease and chronic kidney disease. Here's how these two conditions are related, based on PubMed-type references:

Coronary Artery Calcification (CAC):

• Studies have demonstrated that elevated serum uric acid levels are independently associated with the progression of coronary artery calcification. In individuals without renal disease, serum uric acid was found to predict CAC progression, indicating that uric acid might be a marker for identifying those at risk for vascular disease even in the absence of significant kidney issues. (Kiss, et al., 2019;Rodrigues, et al., 2010)

Aortic Calcification:

• Research has shown a positive correlation between serum uric acid levels and aortic arch calcification (AAC) in middle-aged and elderly populations, particularly among women. This suggests that high uric acid levels may contribute to or be associated with the calcification process in major arteries. (Yan, et al., 2020)

Mechanistic Insights:

• Uric acid may contribute to calcification through various mechanisms, including promoting oxidative stress, endothelial dysfunction, and inflammation, all of which can lead to the development of atherosclerosis and subsequent calcification. Uric acid has been implicated in the activation of pathways that could increase vascular calcification. (Freilich, et al., 2022)

Chronic Kidney Disease (CKD) Context:

• In patients with early chronic kidney disease, serum uric acid levels are associated with coronary artery calcium scores, suggesting that uric acid might play a role in the calcification process in the context of kidney dysfunction. (Han, et al., 2021)

General Population Studies:

• Clinical relevance in broader populations shows that serum uric acid levels correlate with abdominal aortic calcification, hinting at a dose-response relationship where higher uric acid levels are linked with increased calcification scores in men. (Li and Chen, 2020)

These findings collectively suggest that while uric acid might not directly cause calcification, it serves as a significant biomarker for increased risk of vascular calcification, particularly within the framework of cardiovascular and renal health. It's important to recognize that these associations do not necessarily imply causation, and more research is needed to fully understand the mechanisms and direct impact of uric acid on calcification processes.

ARUN KUMAR, @arunkumar3112, Jan 2

“Calcium oxalate, calcium phosphate and Uric acid or urate are the most common crystals (kidney stones) seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons and eventually to chronic kidney failure. @dlifein”

The Vegan Nutritionist Ⓥ, @vegannutrition1, Jan 3, Replying to @vegannutrition1 and @EddieRDMD.

“Animal protein has been shown to increase uric acid, which increases calcium in the blood, which in turn can gather as calcium stones within the kidneys. See here for a study on adolescents: ‘Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12-19 Years: A Cross-Sectional Study’. (Gu, et al., 2022)

‘Eating, Diet, & Nutrition for Kidney Stones; Can I help prevent kidney stones by changing what I eat or drink?’ https://niddk.nih.gov/health-information/urologic-diseases/kidney-stones/eating-diet-nutrition”

Given all that… Grok says that available research shows a strong link between vitamin K2 and vascular calcification, and a strong link between low vitamin K2 is seen in kidney patients along with elevated uric acid and vascular calcification, but neither hyperurecemia or kidney research has directly addressed how vitamin K2 is involved in elevated uric acid. … More research is needed.

How are calcium binding proteins and vitamin K2 deficiency linked to elevated uric acid in the blood? Pubmed type references please.

(Grok AI 25 web pages)

The relationship between calcium binding proteins, vitamin K2 deficiency, and elevated uric acid in the blood is complex and not directly causative but involves several interrelated pathways. Here is an analysis based on available research:

1. Vitamin K2 Deficiency and Calcium Binding Proteins:

• Vitamin K2 primarily activates certain proteins by carboxylating glutamic acid residues, making these proteins capable of binding calcium. Key among these are matrix Gla protein (MGP) and osteocalcin, which are crucial in regulating calcium deposition in blood vessels and bones, respectively. (Maresz, 2015)

• Deficiency in vitamin K2 leads to the production of inactive, uncarboxylated forms of these proteins, particularly MGP, which is a potent inhibitor of vascular calcification. This deficiency can result in improper calcium handling, leading to vascular calcification. (Maresz, 2015)

“An adequate intake of vitamin K₂ has been shown to lower the risk of vascular damage because it activates matrix GLA protein (MGP), which inhibits the deposits of calcium on the walls. Vitamin K, particularly as vitamin K₂, is nearly nonexistent in junk food, with little being consumed even in a healthy Western diet. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels. An increased intake of vitamin K₂ could be a means of lowering calcium-associated health risks.” (Maresz, 2015)

2. Link to Uric Acid:

• Indirect Association: While there isn't direct research linking vitamin K2 deficiency to uric acid levels, there's an indirect pathway through vascular health and metabolic syndrome:

  • Vascular Calcification: Vitamin K2 deficiency might contribute to vascular calcification, which is associated with conditions like metabolic syndrome, where elevated uric acid levels are also common.

  • Inflammation and Oxidative Stress: Vascular calcification can increase inflammation and oxidative stress, factors known to be associated with hyperuricemia.

3. Research Insights:

• Calcium Metabolism and Uric Acid:

  • Studies suggest that disturbances in calcium metabolism, potentially exacerbated by vitamin K2 deficiency, could influence uric acid metabolism. For instance, calcium ions regulate various cellular processes, including those involved in purine metabolism, which can affect uric acid production or excretion. However, specific research linking vitamin K2 deficiency directly to uric acid levels is lacking.

• Chronic Kidney Disease (CKD):

  • In patients with CKD, where both hyperuricemia and vascular calcification are prevalent, research has highlighted:

    • Vitamin K Status: Vitamin K deficiency, particularly of vitamin K2, is prevalent among CKD patients, correlating with increased vascular calcification.

    • Uric Acid: Hyperuricemia in CKD is common due to decreased renal excretion of uric acid. Although not directly linked, the shared context of renal dysfunction might imply a relationship where both vitamin K2 deficiency and uric acid elevation occur due to systemic health decline.

References:

The role of vitamin K in vascular calcification has been extensively discussed in research, but direct links to uric acid are more inferential:

• Vascular Calcification and Vitamin K: Studies like "Vitamin K-dependent proteins and the role of vitamin K2 in the modulation of vascular calcification: a review" discuss the impact of vitamin K2 on vascular health but do not directly address uric acid. (El Asmar, et al., 2014)

• Uric Acid and Kidney Function: "High plasma uric acid concentration: causes and consequences" explores the association of uric acid with renal function and cardiovascular health but does not delve into vitamin K2. (de Oliveira and Burini, 2012)

Conclusion: While there's no direct, well-documented link in PubMed-type references between vitamin K2 deficiency, calcium binding proteins, and elevated uric acid levels, the pathways through vascular calcification and renal health might suggest an indirect relationship where both conditions could coexist in certain disease states like CKD. More research is needed to explore any direct biochemical or physiological connections between these elements.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

Reference List

(Barr, 1990) Barr WG. Uric Acid. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 165. Available from: https://www.ncbi.nlm.nih.gov/books/NBK273/

(de Oliveira and Burini, 2012) de Oliveira, E.P., Burini, R.C. High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr 4, 12 (2012). https://doi.org/10.1186/1758-5996-4-12 https://dmsjournal.biomedcentral.com/articles/10.1186/1758-5996-4-12

(El Asmar, et al., 2014) El Asmar MS, Naoum JJ, Arbid EJ. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. Oman Med J. 2014 May;29(3):172-7. doi: 10.5001/omj.2014.44. PMID: 24936265; PMCID: PMC4052396. https://pmc.ncbi.nlm.nih.gov/articles/PMC4052396/

(Freilich, et al., 2022) Freilich M, Arredondo A, Zonnoor SL, McFarlane IM. Elevated Serum Uric Acid and Cardiovascular Disease: A Review and Potential Therapeutic Interventions. Cureus. 2022 Mar 28;14(3):e23582. doi: 10.7759/cureus.23582. PMID: 35494989; PMCID: PMC9045796. https://pmc.ncbi.nlm.nih.gov/articles/PMC9045796/

(George, et al., 2023) George C, Leslie SW, Minter DA. Hyperuricemia. [Updated 2023 Oct 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459218/

(Gu, et al., 2022) Gu F, Luo X, Jin X, Cai C, Zhao W. Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12-19 Years: A Cross-Sectional Study. Front Med (Lausanne). 2022 Jun 10;9:915371. doi: 10.3389/fmed.2022.915371. PMID: 35755048; PMCID: PMC9226332. https://pmc.ncbi.nlm.nih.gov/articles/PMC9226332/

(Han, et al., 2021) Han, M., Kim, H., Kim, H.J. et al. Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study. BMC Nephrol 22, 247 (2021). https://doi.org/10.1186/s12882-021-02463-2 https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02463-2

(Kiss, et al., 2019) Kiss LZ, Bagyura Z, Csobay-Novák C, Lux Á, Polgár L, Jermendy Á, Soós P, Szelid Z, Maurovich-Horvat P, Becker D, Merkely B. Serum Uric Acid Is Independently Associated with Coronary Calcification in an Asymptomatic Population. J Cardiovasc Transl Res. 2019 Jun;12(3):204-210. doi: 10.1007/s12265-018-9843-8. Epub 2018 Nov 9. PMID: 30414068; PMCID: PMC6611752. https://pmc.ncbi.nlm.nih.gov/articles/PMC6611752/

(Li and Chen, 2020) Li YW, Chen WL. Clinical relevance of serum uric acid and abdominal aortic-calcification in a national survey. Clin Cardiol. 2020 Oct;43(10):1194-1201. doi: 10.1002/clc.23433. Epub 2020 Jul 28. PMID: 32720347; PMCID: PMC7533967. https://pmc.ncbi.nlm.nih.gov/articles/PMC7533967/

(Maresz, 2015) Maresz K. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integr Med (Encinitas). 2015 Feb;14(1):34-9. PMID: 26770129; PMCID: PMC4566462. https://pmc.ncbi.nlm.nih.gov/articles/PMC4566462/

(Rodrigues, et al., 2010) Rodrigues TC, Maahs DM, Johnson RJ, Jalal DI, Kinney GL, Rivard C, Rewers M, Snell-Bergeon JK. Serum uric acid predicts progression of subclinical coronary atherosclerosis in individuals without renal disease. Diabetes Care. 2010 Nov;33(11):2471-3. doi: 10.2337/dc10-1007. Epub 2010 Aug 26. PMID: 20798338; PMCID: PMC2963516. https://pmc.ncbi.nlm.nih.gov/articles/PMC2963516/

(Yan, et al., 2020) Wei Yan, Guoming Sun, Aishu Luo, Shiyu Lin, Jianan Wang, Qiande Zhang, Jintao Jiang, Miaojia Zhang, Fang Wang, Wenfeng Tan, Serum uric acid is independently associated with aortic arch calcification in a cross-sectional study of middle-aged and elderly women, Nutrition, Metabolism and Cardiovascular Diseases, Vol 30(6), 2020, pp 932-938, ISSN 0939-4753, https://doi.org/10.1016/j.numecd.2020.02.015. https://www.sciencedirect.com/science/article/pii/S0939475320300636