What Happens to Supplements in Your Stomach? The 'First Pass' Effect

Do NAD pills actually work? Most oral NAD+ supplements fail to deliver results because they are partially metabolised by your liver before they ever reach your cells [1]. This is called the First Pass Effect. It filters out foreign substances absorbed from your gut, meaning only a tiny fraction of the NAD+ you swallow actually enters your bloodstream to do its job.

• Digestion is destructive: Stomach acid breaks down fragile molecules like NAD+.

• The liver acts as a filter: The First Pass Effect removes most supplements before they enter circulation.

• Size matters: The high molecular weight of NAD+ makes it hard to absorb through the gut wall.

• Injections bypass the loss: Delivering NAD+ subcutaneously skips the liver entirely.

When you swallow a vitamin or supplement, it does not just appear in your blood.

It has to get past biological defences designed to protect you.

For robust chemicals like paracetamol, this is fine. But for fragile molecules like NAD+, it is much harder.

The first stop is your stomach.

Your stomach is highly acidic (pH 1.5 to 3.5). Its job is to dissolve food and kill bacteria.

NAD+ is chemically unstable in acid [2], and some of it may break down before absorption, forming nicotinamide (Vitamin B3)

If you’re taking direct NAD+ orally, only a portion may survive to reach your cells intact.

You aren't getting the longevity molecule you paid for. You are getting a very expensive Vitamin B pill.

Whatever survives the acid moves into the small intestine.

Here, nutrients are absorbed through the intestinal wall and travel into a specific blood vessel called the hepatic portal vein [3].

This vein does not go to your heart or brain. It goes straight to your liver.

This is the body's safety mechanism. It ensures that nothing is absorbed into your main blood supply without being checked first.

This is where the real damage happens.

The liver inspects everything coming from the hepatic portal vein. It sees NAD+ as something to be processed. It breaks it down heavily using enzymes.

This is the First Pass Effect. The concentration of the drug or supplement is drastically reduced before it reaches your systemic circulation.

By the time the blood leaves the liver to go to the rest of your body, the bioavailability (the amount left) is often less than 10%.

There is another physical problem: Size.

NAD+ has a high molecular weight [4]. It is a large, bulky molecule compared to simple sugars or salts.

The cells lining your gut are designed to let small nutrients through. Large molecules like NAD+ struggle to cross the intestinal barrier intact.

This leads to poor NAD+ absorption even before the liver gets involved.

The only way to avoid the First Pass Effect is to skip the liver loop entirely.

This is why doctors use injections for critical medications like insulin. When you use a Vivere pen, you inject into the subcutaneous tissue (fat). The capillaries here drain into veins that bypass the hepatic portal system [5]. The NAD+ enters your general circulation directly.

It enters circulation without being degraded by the stomach or liver, allowing more NAD+ to reach tissues.

Understanding the First Pass Effect changes how you spend your money on health.

It explains why you might not feel different after finishing a bottle of NMN or NAD+ pills. It is not that the molecule doesn't work. It is that the delivery system failed.

If you want the benefits of NAD+, subcutaneous injections offer a convenientway to ensure you get what you pay for.

"The liver is an incredible filter, but for certain therapeutics, it works too well. The 'First Pass Effect' is the primary reason why swallowing NAD+ precursors often yields poor results compared to clinical expectations. By bypassing the hepatic route via injection, we reduce metabolic degradation, allowing more NAD+ to enter systemic circulation."

[1] Nicotinamide riboside is uniquely and orally bioavailable in mice and humans | Nature Communications

[2] The hydrolysis of nicotinamide adenine nucleotide by brush border membranes of rat intestine - PubMed

[3] Full article: Potential role of intestinal first-pass metabolism in the prediction of drug–drug interactions

[4] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings - PubMed

[5] First-pass elimination. Basic concepts and clinical consequences - PubMed