The health community on social media and YouTube has a history of finding a way to demonize a molecule some way or another. 

Coffee and gut-destroying tannins.

Sugar and insulin-mediated metabolic syndrome.

Beef and uric acid causing gout. 

The most popular one lately is without a doubt Oxalates. And how vitamin C intake contributes to higher oxalate levels that lead to oxalate crystal formation. 

Whole-food vegan crowds talk about how it’s synthetic vitamin C (ascorbic acid is an alias for vitamin C by the way) causing oxalate crystals to form. That if only you took whole-food vitamin C in its natural complex you’d be spared. 

Carnivore crowds talk about how it’s any vitamin C-containing plants contributing to oxalosis (a condition where oxalate levels are too high throughout the body).

Let’s not jump to conclusions about vitamin C causing oxalosis without understanding the full picture, and more importantly, without any biases. 

It’s time we sort fact from fiction and show why a half-arsed understanding of biochemistry leads to flawed information–and a continued philosophy of demonizing molecules. 

Why This Matters for Your Everyday Health

If you’ve never heard of oxalates before you might be wondering how this obscure molecule relates to you.

Well, if you want to avoid kidney stones, metabolic issues, and (possibly) cancer, then oxalates matter. They’re another piece of a complex metabolic puzzle. 

Understanding the relationship between vitamin C and oxalates can help you make informed decisions about your diet, supplements, and overall health. It's about taking control of your well-being without falling for every health scare that comes along.

Understanding Oxalates

What Are Oxalates and Where Do They Come From?

Oxalates are a type of organic acid found naturally in plants and bacteria. They act as defense molecules for plants, fuel for certain bacteria, and are byproducts of our metabolism. 

But just like any metabolite, an excess of oxalates can affect our system. The thing is, it doesn’t take more than 50mg of oxalates a day, over a while, for it to have detrimental effects. 

In excess, oxalates can form crystals with calcium. These crystals build up in the kidneys forming kidney stones, and in other tissues like the eyes, causing floaters.

Endogenous Oxalates

As said above, we produce oxalates every day. Oxalates are an end-product of normal metabolism and it’s estimated that about 60-80% of total oxalate per day comes from natural metabolic processes in the liver (1).

So about 20-40% of oxalates come from outside sources, namely, diet. Pretty small amount if you think about it. 

Then just how much would come from vitamin C? As it turns out:

Purely on percentages, any logical person would realize their oxalate issues wouldn’t be solved by cutting out high-oxalate foods or vitamin C even if conversion to oxalates was 100% (it’s nowhere near that).

Let’s go over what does affect oxalate clearance, vitamin C conversion, and how much oxalates someone can tolerate.

Genetic Factors Influencing Oxalate Metabolism

Genes, unsurprisingly, play a big role in oxalate metabolism.

A lot of success in understanding oxalates and how they damage our cells comes from genetic hyperoxaluria. There are two types of hyperoxaluria (type I due to a defect in AGT enzyme, and type II due to a defect in GRHPR enzyme). 

Both types experience much higher levels of oxalates and kidney stones.  

But, even in these high-risk individuals, it’s not always straightforward.

First, these patients have higher oxidative stress in general thanks to more glyoxylate (also converts to oxalates). 

Second, if you give these individuals vitamin C (remember they’re at the highest risk) less than 10% of total oxalates comes from vitamin C, and absolute amounts of oxalates are not increased. This is also for a massive dose of 4 grams (2).

This aligns with the fact that 60-80% of oxalates come from our own metabolism.

Finally, oxalates don’t even seem to be the most detrimental concern in these patients. The elevated activity of an enzyme abbreviated LDH is way more concerning. This enzyme is the same one that is elevated in cancer leading to the “Warburg effect.”

The Warburg effect contributes to an acidic environment super helpful for cancer cells (by H+ ion accumulation), and widespread inflammation from even more glyoxylate. Enter… point #1 all over again.

Welp, there goes the whole argument of “vItaMiN c wiLL cAuSe OxAlaTes mAn”...

But let’s not stop there!

How The Heck Would Vitamin C Even Contribute?

Don’t Skip Chemistry, Man

We can tell who in the health community skipped out on chemistry because the answer to how vitamin C converts to oxalates, and the conditions required for this, are all there. 

In other words, you can solve the vitamin C controversy purely with chemical knowledge alone.

All the rest is fluff. But we’ll go over it anyway. 

Ideally, we’d do a full organic chemistry breakdown but then you’d skip over this section so we’ll summarize it in one full reaction. 

Recall, vitamin C = ascorbic acid.

Ascorbic acid (AA) gets oxidized → becomes Dehydroascorbic acid (DHA). Then you need reactive oxygen species or free metals for DHA to oxidize further to → 2,3-diketogulonic acid (DKG). DKG then gets cleaved, since it’s an unstable molecule, to → oxalate and threonic acid. 

In total: AA → DHA → (under oxidative conditions) DKG → oxalate + threonic acid.

Do you recognize the caveat here? Vitamin C only becomes oxalate when people are under high loads of oxidative stress! No one ever mentions this!

Another strike for the vitamin C controversy…

No One Has a Clue 

To date, there’s no confirmed value of how much vitamin C gets converted to oxalates, in either healthy or unhealthy people. So many studies differ!

Why?

A couple of reasons:

Check it out…

1. Higher Supplement Intake:

○ When daily vitamin C intake exceeds 1000 mg, urine levels of oxalates increase by:

Why does the higher dose group have somehow less oxalates in urine than the lower dose? Maybe this is why:

○ People who took up to 1000mg of vitamin C had about 6.8mg of extra oxalates in their urine.

Seems like a lot right? Well, do you know how much oxalates are in a cup of spinach? 658mg. In 100g of sweet potatoes? 28mg of oxalates. Come on man…

3. High-dose Intravenous Infusion:

○ Very high IV doses (up to 60 g which is just insane) used in patients led to notable increases in serum oxalate and, in severe cases, oxalate nephropathy due to excessive oxalate production. The exact conversion rates are unclear but suggest significant risk at high concentrations​.

What isn’t mentioned:

NONE of these people were healthy! Prostate cancer for one, another with lupus, a burn victim, and almost all the others on dialysis. Of course, you’re going to see higher kidney disease from vitamin C in these cases.

Clearly, the devil is in the details and if you don’t look carefully, you can easily be misled in this vitamin C controversy.

(3).

The Enzyme Factor

Now that we’ve explained why vitamin C is not a big player, we can get to the heart of the issue when it comes to oxalates.

The situation we find ourselves in is a couple of key influencers missing the mark about vitamin C because they lack the full picture of oxalate metabolism.

As we’ve learned, collagen, oxidative stress, heavy metals, and glyoxylate are much more important players in oxalate metabolism than vitamin C. 

This is where four key enzymes come in; AGT, GRHPR, KAT3, and LDH.

Lesser Known Enzymes are Key Players in Oxalate Metabolism

AGT and GRHPR: Preventing Excess Oxalates

Meet the unsung heroes of our story: enzymes like AGT and GRHPR. These enzymes help convert the precursors of oxalate, namely, glyoxylate into glycine, pyruvate, and glycolate. Reducing the amount that gets converted to oxalate (2). 

KAT3: The Kidney's Role in Glyoxylate Conversion

KAT3 is like the kidney's secret weapon against oxalate buildup. This is another that enzyme helps convert glyoxylate into glycine, reducing oxalate formation. It's highly expressed in the kidneys too, and defects in this enzyme may explain issues with oxalates in sensitive individuals (4).

LDH: Its Dual Role in Metabolism and Disease

LDH is the “good guy turned bad” of enzymes. 

When LDH is overactive, not only do we get more conversion of glyoxylate to oxalate, but also more oxidative stress from lactate accumulation (5). Taking vitamin C in this state will lead to it getting the bad rap making everyone think it’s increasing oxalate levels.  

Environmental and Dietary Influences

Oxidative Stress and Its Impact on Oxalate Formation

Oxidative stress – it's not just a buzzword. This cellular stress can accelerate the breakdown of vitamin C into oxalate. It's like your body's way of crying for help, but instead of tears, you get oxalate crystals.

The Role of pH in Oxalate Production

Your body's pH levels can tip the scales in oxalate production. An overly acidic environment might promote more oxalate formation. It's like your internal chemistry set decided to experiment without your permission.

How Food Storage Affects Oxalate Content

Here's a twist: how you store your food can affect its oxalate content. Is that spinach sitting in your fridge for a week? It might be developing more oxalates over time. It's like your vegetables are plotting against you.

This is especially common for vegetables in particular. 

There goes that rhubarb-strawberry pie…

B-Vitamins Role in Oxalate Metabolism

Enter vitamin B6, the unsung hero in our oxalate controversy. This vitamin is crucial for the proper functioning of those oxalate-busting enzymes we talked about earlier. Without enough B6, those enzymes are like bouncers asleep on the job, letting oxalate metabolism run amok.

B6 is a cofactor in the enzyme AGT, and KAT3, immediately helping with any issues oxalate-related.

B3 is a cofactor for GRHPR. 

And B1 helps reduce LDH activity by lowering lactate levels. 

Altogether, you get a nice oxidative stress-reducing entourage too!

Beyond Vitamin C: Other Oxalate Considerations

High-Oxalate Foods and Their Impact

While we've been focusing on vitamin C, let's not forget that many foods are high in oxalates. Spinach, nuts, chocolate, even sweet potatoes can be oxalate bombs.

If you have high oxalate foods, with high vitamin C intake, then obviously you’re not doing your system any good.

If you’re stressed, your body is in a state of high oxidative stress. Consuming oxalate-ridden foods then can worsen the issue, and taking high doses of vitamin C without other antioxidants can be a double-whammy.

Genetic Variations Affecting Oxalate Processing

Remember how we talked about genes playing a role? Some people are genetically predisposed to have issues with oxalate metabolism.

So far we’ve mentioned LDH, AGT, KAT3, and GRHPR. There may be others when you consider that it’s only within the last five years that KAT3 has been considered important!

So keep in mind that if you’re someone sensitive to oxalates or their related metabolic pathways, and you feel like vitamin C worsens you, it could be a genetic susceptibility!

Conclusion: It’s NOT the Dang OJ Man

Summarizing Key Points About Vitamin C and Oxalates

So, what have we learned? Vitamin C isn't the oxalate-producing villain it's been made out to be. It's one player in a complex metabolic game, influenced by enzymes, other vitamins, your genes, and even how you store your food.

And if anything, we have no idea how much vitamin C converts to oxalates in healthy, non-susceptible humans vs. sick, susceptible humans.

More importantly, we learned that health influencers really skip the big-picture stuff because of their agenda or bias. 

Practical Tips for Managing Oxalate Intake

If you're concerned about oxalates, consider these tips: balance your diet, don't overdo it on vitamin C supplements, ensure adequate B1, B3, and B6 intake, and maybe don't let your spinach sit in the fridge for weeks. It's about smart choices, not drastic eliminations.

Also, calcium intake is important. The more calcium you consume, the more protected from oxalates you are (6). 

Oh yeah, almost forgot… remember how we said to get that cup of OJ? It turns out that the citric acid naturally present in citrus fruits is super protective against oxalates (6). The irony! 

The Importance of a Balanced Diet and Informed Nutrition Choices

In the end, it all comes down to balance and informed choices. Demonizing vitamin C (or any single nutrient) is like trying to understand a symphony by listening to just one instrument. Appreciate the complexity of your body, make informed decisions, and remember–a little chemistry knowledge goes a long way in navigating the sometimes confusing world of nutrition.

So the next time someone tries to claim your OJ is killing you, armed with oxalate fear-mongering, you can smile. You've been through the metabolic trenches. You've seen the enzyme battles. You know the truth. And the truth is, vitamin C is a miracle vitamin. Here's to informed eating and never fearing your OJ again.