Key Takeaways
- Your genetics, gut health, and metabolism influence how your body absorbs and utilises supplements.
- The quality, dosage, and form of a supplement determine its effectiveness—some are far better absorbed than others.
- Longevity supplements like NMN and NR depend on individual factors such as NAD+ metabolism, cellular uptake, and genetic differences in response.
Did you know that two people can take the exact same supplement, at the same dose, and experience completely different results? This isn’t just anecdotal—it’s backed by science.
Your body’s ability to absorb and utilise supplements is influenced by multiple factors, from genetics and gut health to the form of the supplement itself. If you’ve ever wondered why some supplements seem to work wonders for one person but do nothing for another, this blog will break it all down.
Your Genetics Determine How You Process Nutrients
Genetics plays a major role in how your body absorbs and utilises vitamins, minerals, and other nutrients. Specific genes control the production of enzymes that help break down and metabolise nutrients from food and supplements (R).
For example, variations in the MTHFR gene impact how efficiently your body converts folic acid (a synthetic form of folate) into its active form, methylfolate (R). If you have a mutation in this gene, taking standard folic acid supplements may not benefit you as much as taking methylated folate (5-MTHF), which is already in its active state.
Similarly, the FUT2 gene influences how efficiently you absorb vitamin B12. Certain variants of the FUT2 gene are associated with a reduced ability to absorb B12 from food, increasing the risk of deficiency. People with these variants may benefit from sublingual or injectable forms of B12 for better absorption. Methylcobalamin, a bioactive form of B12, may be particularly beneficial for individuals with absorption challenges due to genetic factors (R).
Genetic testing can help determine which forms of supplements your body can actually use, making supplementation more personalised and effective.
The Role of Your Gut Microbiome in Supplement Absorption
Your gut is home to trillions of bacteria that play a crucial role in nutrient absorption. If your microbiome is out of balance—due to poor diet, stress, antibiotics, or gut conditions—it can hinder your ability to absorb and benefit from supplements.
A prime example is magnesium, an essential mineral that requires a healthy gut lining for optimal absorption. Conditions such as leaky gut, irritable bowel syndrome (IBS), and Crohn’s disease can impair nutrient absorption, potentially leading to magnesium deficiency.
Additionally, certain gut bacteria are responsible for activating vitamin D in your body. If your gut microbiome is compromised, even if you take high doses of vitamin D, your body may not convert it into its active form (calcitriol) efficiently (R).
Supporting your gut health through probiotics, fibre, and fermented foods can enhance the effectiveness of your supplements.
Not All Supplements Are Created Equal
The quality, form, and dosage of a supplement can significantly impact how well your body absorbs it. For example, magnesium oxide—a cheap form found in many multivitamins—has poor bioavailability, meaning your body absorbs only a small fraction of it (R). On the other hand as previously mentioned, magnesium malate is much better absorbed and less likely to cause digestive issues.
Another example is curcumin, the active compound in turmeric. On its own, curcumin has low bioavailability, but when combined with black pepper extract (piperine), absorption increases by up to 2000% (R).
When choosing supplements, look for activated, methylated, or liposomal forms, which are designed to enhance absorption.
Medications Can Block or Deplete Nutrients
Many common medications interfere with nutrient absorption, which may explain why some supplements don’t seem to work for you.
- Proton pump inhibitors (PPIs), used for acid reflux, reduce stomach acid, making it harder to absorb magnesium, calcium, and vitamin B12 (R).
- Oral contraceptives have been shown to deplete B vitamins, zinc, and magnesium, leading to deficiencies over time (R).
- Metformin, a common diabetes medication, reduces B12 absorption, which can lead to fatigue, nerve issues, and cognitive decline (R).
If you take medication, discuss possible interactions with the your doctor, you may need to adjust supplement dosages or take specific forms that bypass these interactions.
Why NMN and NR Work for Some but Not for Others
Longevity supplements like NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are designed to boost NAD+ levels, a critical coenzyme involved in cellular energy, DNA repair, and ageing. Although most report benefits, not everyone responds to these supplements in the same way, here’s some potential reasons behind why:
NAD+ Levels May Already Be Sufficient
Some people naturally maintain higher NAD+ levels due to their age, genetics, and lifestyle habits. If your NAD+ levels are already optimal, supplementing with NMN or NR may not provide noticeable benefits (R).
Poor Absorption or Conversion
Certain genetic and biological factors can reduce the efficiency of converting NMN and NR into NAD+, impacting their effectiveness. Genetic variants in NAMPT, CD38, NRK1/NRK2, and NAPRT can impair NAD+ synthesis, while high CD38 activity (which increases with age and inflammation) accelerates NAD+ depletion.
Absorption challenges, such as low NMN transporter activity (Slc12a8), NR instability, and gut microbiome imbalances, may further reduce bioavailability (R).
Gut Microbiome Influence
The gut microbiome plays a role in breaking down and absorbing NMN and NR. An imbalanced gut may metabolise these compounds too quickly, reducing their effectiveness before they reach the bloodstream (R).
Lifestyle Factors Matter
NAD+ declines naturally with age, but lifestyle factors such as fasting, exercise, and quality sleep can enhance its production. If you’re leading an already optimised lifestyle, NMN and NR may offer less noticeable effects (R).
Dosage and Supplement Quality
Not all NMN and NR supplements are created at the same level of AgeMate quality. Stability, purity, and formulation impact how well they work. Low-quality supplements may degrade quickly, reducing their effectiveness (R).
If NMN or NR hasn’t worked for you, considering alternative strategies like fasting, exercise, and sirtuin-activating compounds (resveratrol, spermidine) may be more effective for optimising NAD+ levels.
Personalised Nutrition Is the Future
The reason supplements work for some but not others comes down to bio-individuality—your genetics, gut health, diet, and lifestyle all determine how well you absorb and use nutrients. Choosing high-quality, well-absorbed supplements, optimising your gut health, and making small lifestyle tweaks can make a big difference in whether you see results.
If you’re interested in learning more about how to choose the right supplements for longevity, check out The World of Longevity Supplements Explained for science-backed recommendations.
