Is this one (1) of the most important nutritional supplements?

Betaine HCL Pepsin

When it comes to “Supplements” in any health wellness blog, almost any pedestrian would assume the author must be an absolute figure of authority in such use and/or praise.

I am “shy” however, when it comes to portraying such ego. Due to increasingly flux of Internet SJW’s, thought-polices, and their moral pitchforks – I’ve been keeping this quietly so to speak.

Betaine HCL + Pepsin.

Or technically known as TMG (Trimethylglycine). Usually accompanied by Pepsin (“πέψις” /pepsis / “Digestion”). These have been the forefront / focus for nutrient partitioning. Protein, amino acid digestion, utilisation, uptake, then all the way to numerously complex and ornate biochemistry – Methylation.

This article is only contemplative not prescriptive. Those who need detail requires very nuanced understanding of Methylation. “Methylation” itself ~ is never an easy subject for anyone to grasp. Because it shares Biochemistry (molecules, biomolecules, macros & micros) and Neuroscience (neuropeptides, transmitters and brain health). Hence by no means this article is an “Authoritative” figure of reference so to speak. This is simply a sharing of cliff notes of various research and studies. You are encouraged to find and curate your own research. And at best ~ self-enquire all supplementation strategies in periodical dosages between none, habitual or high. AW™.

Another disclaimer ~ This is not a permission for anyone to go all out on massive dosing of Betaine or Betaine HCL+Pepsin. Please consider the following starter points:

  • Start small this appears to be sage & pragmatic advice. Never by its own. Take it as soon as first bite of protein source. 
  • It appears that Betaine HCL and that of TMG (Betaine Anhydrous): are both methyl donors, and shares the “same basic chemical formula”.
  • Many advocates on increasing dosage to raise tolerance. Common dosages range of 325mg – 650mg. If I am anticipating a big mixed-macros meal/s, such as in context of refeed(s) or social events ~ a raised dosage seems warranted.  
  • Some sources suggest taking it every day and every meal time. Pragmatically, I would gradually reduce dosage should I feel “no need” for it ~ which indicate signs for possible re-acclimatisations of the stomach for it to “retrain”.
  • There is some concern that it may adversely interact with Aspirin. A pragmatic advice would be to take each far and away separately.

The “why”.

Back ever since many years (even before my standard Standard Keto early days back in 2014-2016) ~ I always had lingering feelings of unease, inflammations and/or just general feeling as though food – almost any solid foods – did not “sit” nor settle as they should be. I always thought it’d be a matter of stoicism. Man it up. Little do I know all this is damage, all along

So I started my own nutritional journalling. Put my curiosity put to the test against the undying  status quo ~ “Acidity is bad, period.”

Betaine HCL + pepsin ~ was a revelation. For many years that pass, my reliance on these gradually reduced to almost none. Except in few circumstances whereby much higher calorie feedings or mixed macro re-feeding scenarios are anticipated.

Over the years of SKD and now CKD+IF ~ I used to have persistent reliance on these. Thankfully, physiology corrects itself overtime. This is also attributed perhaps that I also became more critical in my choice of foods during refeeds. As well ~ maintaining other arguably-crucial, supporting micronutrients for digestion health. Namely, Zinc, Magnesium, Vitamin D, K2, COQ10 (only occasional) & Creatine. 

Products I took

So what “products” or “brands am I taking?

  • “Nature’s Life®” as pictured above – combines betaine HCL 350MG (“5.4 grains”), Calcium Carbonate (15mg) and Pepsin 45mg (1:10,000) Equivalent to 150mg. Average pricing from Ebay® sellers range from $20 to $25. This can be bought ocassaoinlly perhaps no more than twice a year (unless if one is severely under clinical advice or suspected towards achlyrodia).
  • Alternatively in the past I have bought betaine HCL crystal powders by the bulk. 100g-250g between $15-$20. Beware however  this requires more precise dosage. Yes, this technically last for quite a long time.

I would not recommend, unless you’re pocket rich ~ the DIY crystal powders approach. This requires you to not only buy a mini/micro capsule filling station ($15-$25), but also need to buy the gelatine capsules. The size I used for this as I best approximate on dosage is “Size 3” as I best recall.  And also obviously ~ I had to buy the pepsin powders separately ($15-$25).

The amount of time and labour it took me, from memory (as I did not have a proper filling capsule station) ~ was almost not worth it. But, for those who plan to really go all out on DIY supplementing the capsule filling station + outsourcing your own gelatine capsules may yet be cost effective if you also are DIY’ing many supplements. Especially in huge quantities / amounts.

But for the everyday pragmatic user. There’s always other priorities. Namely “food”. Before you ask, no I am not “paid” by anyone.

The Research

A first general stop would be’s excellent article on TMG.

Otherwise, much of what I provide here is only a sharing of noteworthy passages / findings  from studies that surrounds the general importance(s) of acidity for strong and able nutritive health. Not just praiseful claims from direct use of Betaine HCL /  Pepsin. These are categorised into four (4) categories: Digestion, Viral Infections, Psychological/Psychosocial and lastly Metabolic Markers.

1/4 Digestion

“Numerous studies have shown acid secretion declines with advancing age. The resultant rise in stomach pH can have a detrimental impact on nutrient absorption and may increase the risk of a variety of clinical conditions.”

Gregory S. Kelly, N.D.  Hydrochloric Acid: Physiological Functions and Clinical Implications.

“After being told I had IBS when several tests came back normal, I was determined to find the cause of my gut issues. The most valuable information and guidance came from working with my functional nutritionist. I can now live my life normally with no worries that I will have pain after I eat. After 2 years of mystery pains, I am pain free. I am forever grateful.”

Kasia Kines, et al. Nutritional Interventions for Gastroesophageal Reflux, Irritable Bowel Syndrome, and Hypochlorhydria: A Case Report

“Low HCL levels in the stomach occur frequently in the elderly, in people with some types of stomach disorders, and when any of several types of antacid drugs are used. This low HCL can prevent minerals from separating from food or supplements. If mineral separation has already occurred, low HCL can allow the minerals to recombine into compounds that are difficult to absorb.”

Gerber, J.  A Review of Mineral Absorption with Special Consideration of Chelation as a Method to Improve Bioavailability of Mineral Supplements.

“Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions.”

Recker RR. “Calcium absorption and achlorhydria.”

“Stomach acid markedly increases dissolution and ionization of poorly soluble calcium salts. If acid is not properly secreted, calcium salts are minimally dissolved (ionized) and, subsequently, may not be properly and effectively absorbed. Atrophic gastritis, gastric surgery, and high-dose, long-term use of antisecretory drugs markedly reduce acid secretion.”

Sipponen P & Härkönen M.Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis?”

2/4 Viral Infection from lack of acidity

“According to the Textbook of Functional Medicine, low stomach acid predisposes one to the growth of H. pylori and is also linked to SIBO and inadequate Vitamin B12 absorption. It’s also noted that low levels of vitamin C, and vitamin E in gastric fluids promote the growth of H. pylori. And while there aren’t decisive studies showing that H. pylori is the direct cause of heartburn and acid reflux, there is an implied association there.”

Peter Bennett et al. 2010. Textbook of Functional Medicine 2010.

“If low stomach acid is a prerequisite to H. pylori infection, we might expect acid suppressing drugs to worsen current H. pylori infections and increase rates of infection. That’s exactly what studies suggest. Prilosec and other acid suppressing drugs increase gastritis (inflammation of the stomach) and epithelial lesions in the corpus of the stomach in people infected with H. pylori.”

Chris Kesser. More-evidence-to-support-the-theory-that-gerd-is-caused-by-bacterial-overgrowth.

The Japanese seemed to have many incidences of stomach cancers.

“Histologically, gastric cancer is classified as either “intestinal” or “diffuse”. Intestinal cancer is commoner and is associated with atrophy and IM while diffuse cancer tends to arise in areas of active inflammation. Both are strongly associated with H pylori infection….Cytokine production is largely responsible for the host’s inflammatory response to H pylori infection and is genetically determined. Interleukin (IL) 1β and tumour necrosis factor α (TNF‐α) are proinflammatory cytokines that also inhibit acid production.”

G M Naylor et al.Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients.

“Potent acid suppression has long been suspected a risk factor of gastric cancer by worsening gastric atrophy with ensuing hypergastrinemia and bacterial overgrowth in the stomach….During a mean follow up of 6.9 years, PPI use was associated with an increased gastric cancer risk (HR 3.61; 95% CI 1.49–8.77). Such an association was only observed among patients with intestinal metaplasia, indicating PPIs potentially increase gastric cancer risk in patients with pre-existing gastric precancerous lesions.”

Cheung K S, et al. “Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence.”

“Aromatic amino acid metabolism (specifically tyrosine, phenylalanine, and tryptophan) may be dysfunctional in gastroesophageal cancer.” 

Wiggins, T et al. See attached study as: Lai H-SLee J-CLee P-HWang S-TChen W-JPlasma free amino acid profile in cancer patients.Semin Cancer Biol 2005;15:26776.

3/4 Pscyhological / psychosocial precursors for digestion.

Bit of context background (personal)

Many years ago throughout 2008-2011 – I was reliant on “S-AME” or technically elaborated as  s-adenosylmethionine supplementation. Mainly for its anti-depressive effects and anti-joint pain during mid workouts. It appears that TMG is the required cofactor.

“TMG has been proposed as a treatment for depression. In theory, it would increase S-adenosylmethionine (SAMe) by remethylating homocysteine. The same homocysteine-to-methionine result could be achieved by supplementing with folic acid and vitamin B12, methionine then serving as a precursor to synthesis of SAMe. SAMe as a dietary supplement has been shown to work as a nonspecific antidepressant.”

Wikipedia®. Attached reference as Mischoulon D, Fava M (2002). “Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence”. Am. J. Clin. Nutr76 (5): 1158S–61S.

“In general, protein intake and a relaxed emotional state tend to increase stomach acidity.”

Gregory S. Kelly, N.D.  Hydrochloric Acid: Physiological Functions and Clinical Implications.

“Excess cortisol not only reduces the production and secretion of hydrochloric acid (HCL) , an essential piece to the signals being sent down the tract, it also compromises the body’s first line of defense, secretory IgA (ie. your immune system)….Remember, from an evolutionary point of view, stress is the body’s signal to run like hell and digestion is not a priority when running for your life.”

East West Healing. “Hypothyroidism and Leaky Gut”

4/4 Metabolic markers / Insulin / thyroid health

“Just as hypothyroidism can result in the drying out of your skin and hair, it also seems to lower the levels of stomach acid in many thyroid patients, possibly by lowering your amount of parietel cells or lowering their ability to produce gastric acid, aka hypochlorhydria.  The result?  The absorption of important nutrients is reduced, and you can find yourself with non-optimal or low levels of iron, B12, Vitamin D and more.”

Stop The Thyroid Madness.

“Diabetics with high fasting blood sugars (FBS) require a much greater dose of insulin, compared with nondiabetics, to obtain the same critical hypoglycemic level or again the gastric secretory response will not become manifest. “

Michael A. Polacek, MDEdwin H. Ellison, MD  “Insulin-Induced Stimulation of Gastric Acid Secretion”

“Our findings demonstrate clear associations between insulin resistance, metabolic syndrome and GERD. Whether reducing insulin resistance may improve GERD symptoms or EO deserves prospective study.”

Hsu, et al.  Increasing insulin resistance is associated with increased severity and prevalence of gastro-oesophageal reflux disease.

“Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle….Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance.”

Jingjing Du, et al.
Self Enquiry / Journalling Tutorial
Self Enquiry / Journalling Tutorial

In Closing.

Betaine HCL Pepsin has been an eye-opener, at least from my own N=1 account and history. I stress this is still a matter of individual introspection. That Betaine HCL+Pepsin certainly is not for everyone persistently in long term. As long term research as I am aware is not easily found thus far.

The question that remains is what happens if we do not have the money? In my manuscript I’ve suggested various alternatives although sadly these still must constitute additional finances as follows:

  • Consider DIY sauerkrauts and/or DIY Yoghurts. Trust me yourself ~ all that time spent meal prepping ~ you’re being productive and meaningful throughout long IF / fasting hours.
  • Regular / habitual warm ACV Drinks.
  • Gelatin (my blog article + dessert recipe here) . Gelatin powders need not be costly.
  • Mandatory mineral supplementations (MG/ZNG), fat solubles ~ D and/or K2. These are almost non negotiable.
  • Methylation supports water soluble / fat soluble (Creatine, COQ10). Yes, “Creatine”.

Very rarely if ever – do I put out thoughts on supplements like this.  Because I do not proclaim my own N=1 ~ to be the irrefutable gospel ~ as boldly as what many anticipate amidst health / wellness spheres .

Nevertheless, I hope all the above helps provide you informed consent ~ for N=1 self-enquiring / nutritional journalling.




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