Sixty Minutes of Acid: The Brief, Bright Work of Betaine HCl

A forgotten pharmacy trick, hiding in plain sight

For most of the 20th century, pharmacies sold acidifying mixtures—betaine hydrochloride (BHCl), pepsin, even diluted hydrochloric acid—as over-the-counter "stomach acidifiers." Then in 1993 regulators drew a line: there wasn't adequate evidence these products treated low stomach acid (hypochlorhydria), so none could be considered "generally recognized as safe and effective" for OTC use.^[2] As the Code of Federal Regulations still puts it, "any OTC drug product..offered for use as a stomach acidifier cannot be considered generally recognized as safe and effective."^[2] That's the paradox: a supplement long sold for digestion but officially not recognized to treat low acid. And yet, in the last decade, researchers have used BHCl for something precise and measurable: to briefly restore stomach acidity when it's been dialed down—by medication, by food, or by surgery—and watch what changes.

The minute hand: when acidity returns on cue

In a small, tightly controlled trial at UCSF and Stanford, volunteers first took a proton-pump inhibitor (rabeprazole) to push their stomach pH above 4. Then came the test: a single 1,500 mg BHCl capsule. Within about six minutes on average, the stomach slipped back below pH 3, and for roughly an hour it stayed acidic before drifting upward again. The pH drop was dramatic—from around 5 to under 1 at its sharpest—yet temporary.^[3] In short: BHCl can the gastric "acid dial" down, then back up, then let it fade—on a schedule.^[3]

"Betaine HCl was effective at temporarily lowering gastric pH."^[3]

That one-hour window turned out to be more than a party trick.

When acidity decides a cancer drug's fate

Many modern oral cancer drugs are weak bases; they dissolve well in strong acid and poorly when the stomach is neutral. In healthy volunteers, the acid blocker had slashed exposure to dasatinib—a leukemia drug—by 78%. Add back a single 1,500 mg dose of BHCl with the pill, and drug levels snapped back to essentially normal.^[4] The stomach didn't need to be acidic all day; it needed to be acidic at the exact moment the pill dissolved. Clinicians have tried other workarounds, too. In lung cancer patients on PPIs, simply taking erlotinib with cola nudged its exposure up by about 39%, because the acidic drink briefly re-sharpened the stomach's solvent power.^[5] "A possible option," as one clinical commentary put it, "could be temporary gastric reacidification" at dosing time.^[6]

Food complicates the plot

Meals are their own chemistry set. After eating, gastric pH rises for a while, which can frustrate the absorption of acid-loving medicines. In a randomized crossover study, returning post-meal acidity to baseline without help took about 50 minutes; with BHCl, researchers needed larger amounts—about 4,500 mg—to re-acidify within ~17 minutes.^[7] Same molecule, different dose, because food buffers acid like a sponge.^[7]

A patient story: rebuilding appetite after surgery

What about digestion beyond pills? A recent case report followed a man after esophagectomy who battled dumping symptoms and malnutrition. Adding a capsule containing 500 mg BHCl with pepsin before protein-rich meals eased symptoms, restored his appetite, and helped him regain lost weight; stopping the supplement brought the problems back, and restarting it helped again.^[8] It's just one case, but it underscores a plausible role: supplying acid and a protein-shearing enzyme when surgery or disease has left the stomach's chemistry blunted.

What low acid does to a body

When the stomach's "acid firewall" drops, protein digestion stutters, B12 and iron absorption falter, and microbes you'd usually kill can pass through. Clinicians flag links to bloating, malabsorption, and even bacterial overgrowth when acid stays low.^[9] None of this proves BHCl will fix such issues broadly—but it explains why some people feel better when the gastric dial clicks back toward acid, at least for a meal.

Practical ways readers actually use it (and why care is essential)

If BHCl has a role, it's precise and time-bound: with the first bites of a protein-rich meal, or alongside a drug that needs acid to dissolve. Research-grade doses range from 1,500 mg on an empty stomach to about 4,500 mg after a meal to overcome food's buffering.^[3][7] Most retail products pair BHCl with pepsin—mimicking the stomach's natural duet. But acid isn't benign. People with active ulcers, erosive esophagitis, or a history of GI bleeding should avoid adding acid; and anyone on medications whose absorption depends critically on stomach pH should only consider BHCl with clinician oversight.^[2][9][10] Also, don't confuse BHCl with betaine anhydrous (TMG), a methyl-donor nutrient used for homocystinuria and metabolic support; the names overlap because both trace back to beets, but their purposes diverge.^[1]

So where does the evidence leave us?

Here's the honest synthesis:

• BHCl reliably, briefly lowers gastric pH in humans. Multiple crossover trials show a fast onset (minutes) and a short tail (about an hour).^[3][7]
• That window can rescue the absorption of some weak-base drugs during PPI therapy. Human data exist for dasatinib; acidic drinks help erlotinib.^[4][5]
• Symptom relief for digestion is less studied. Beyond physiology and case reports, we lack large trials showing improved dyspepsia or nutrient status with BHCl over weeks or months.^[2][8]

In other words, BHCl looks less like an everyday digestive panacea and more like a timed tool: a match you strike for a specific task, then let burn out.

What's next

Future work will likely focus on two fronts: (1) pairing acidification strategies (BHCl or acidic beverages) with pH-sensitive drugs to optimize dosing in patients who must stay on PPIs, and (2) rigorous trials in postsurgical or documented hypochlorhydria populations to see if targeted, per-meal acidification changes symptoms, nutrient status, or microbiome patterns over months. For now, the story is intriguing and bounded—one bright hour of acid, used wisely.