Why vitamin deficiencies aren't always solved with supplements

You get tested: the readings are either at the lower limit of normal or well beyond. The doctor recommends supplements. You take them for a month, two, three. You get tested again: almost nothing has changed. Sounds familiar?

This is not an isolated case. Vitamin deficiencies that do not respond to standard treatment are one of the most common mysteries in preventive medicine. And the answer sometimes lies in the dosage or quality of the drug.

The problem often lies not with the pill itself, but with how effectively the body can obtain the necessary substances from it.

If you want to figure out if there is a genetic component in your case, — learn about the genetic characteristics of vitamin and mineral absorption.

From pill to cell — a long journey

When a vitamin or mineral enters the body, it goes through several stages: absorption in the intestines, transportation through the blood, conversion to an active form, and finally utilization inside the cell. At each of these steps, something can go wrong.

 Imagine a conveyor belt with four links. If one of them works slower than the others, the entire chain slows down. A blood test can show “normal” levels because it only records what is circulating in the blood, not what is actually available to the cells. 

The most common example is vitamin D. Two people with the same blood levels of vitamin D can experience completely different health outcomes: one feels better after a course of supplementation, the other doesn’t. It turns out that the reason may lie in how effectively cell receptors respond to vitamin D—an inherited trait that a standard blood test doesn’t pick up.

Why does the same pill give different results in two people?

The absorption of vitamins and minerals is not just chemistry. It's chemistry is controlled by enzymes and transport proteins. And the genes that code for these enzymes vary from person to person.

 A few well-studied examples of where the chain breaks:

• Folic acid is a synthetic form of vitamin B9. In order for the body to use it, it must undergo several stages of conversion and become the active form - 5-methyltetrahydrofolate (5-MTHF). An important role in this process is played by the enzyme methylenetetrahydrofolate reductase (MTHFR). The effectiveness of this enzyme depends on the specific genetic variant. In some people, this process is genetically slowed, and the standard dose may not be effective enough, even if a blood test does not show an obvious deficiency (Hecker et al.,Cureus, 2025). This is especially important for women of reproductive age and people with elevated homocysteine ​​levels.

• Vitamin A enters the body in two ways: directly from animal products or through the conversion of beta-carotene from plant foods such as carrots, pumpkin, spinach. The efficiency of this conversion is also controlled by an enzyme with hereditary variability (β-carotene-15,15'-monooxygenase, which is encoded by the geneBCO1). Some people have a much lower absorption of beta-carotene from plant foods, and a vegan diet, which theoretically should cover the need for vitamin A, may not do so in practice (Suzuki & Tomita,Front Nutr, 2022).

• Vitamin B12enters the body through a complex mechanism: first it must bind to a special protein in the stomach, then be transported through the intestinal wall.This process depends on a number of transport proteins, including GIF (intrinsic factor), CUBN (cubilin), and AMN (amnionless). 2020+ studies show that genetic variability in these systems, as well as in transcobalamin transport proteins, can affect the efficiency of B12 absorption and its availability to tissues (Guéant et al.,Life is short., 2022). In clinical practice, this means that vitamin B12 deficiency is not always due to insufficient intake. It is often due to impaired absorption or transport, which can lead to low blood levels of B12 even with an adequate diet. Recent reviews emphasize that such a “functional deficiency” is an underestimated cause of chronic fatigue, anemia, and neurological symptoms, especially in people with age-related changes in the stomach or genetic variability in transport proteins (Elangovan & Baruteau,Front Pharmacol, 2022).

• Magnesium involved in over 300 enzymatic reactions, from energy production to DNA synthesis. However, its actual bioavailability depends not only on dietary intake but also on the efficiency of intestinal absorption and renal reabsorption. These processes are partly regulated by transport proteins, in particular channelsTRPM6andTRPM7,whose activity may vary between people due to genetic differences (Yin et al.,Mol Nutr Food Res, 2023)As a result, the amount of magnesium that is actually “retained” by the body is determined by a combination of diet, kidney function, and the genetically determined efficiency of transport systems.

The same goes for iron, calcium, vitamin K, zinc, iodine—each has its own “bottlenecks” where hereditary characteristics can be a decisive factor (Madeo et al.,Clin Ter, 2023; Valenzuela-Vallejo et al.,Genes Nutr, 2025).

What a blood test shows and what it doesn't

Laboratory analysis for vitamins and minerals is a valuable tool. It records the current level of a substance in the blood and reflects the state at the time of the analysis. This is an important reference point. 

But it doesn't answer the question: Why is this level the way it is? Is the body effectively using what's in the blood? Is there a genetic component that should be considered when choosing a form or dosage of supplements?

A blood test is a snapshot. A genetic test is an instruction manual for the mechanism. They do not replace each other, but complement each other.

There is one more nuance. The results of the blood test vary depending on what you ate the day before, whether you took supplements, as well as the state of the digestive system, in particular the efficiency of absorption in the intestine. Genetic features of absorption are stable throughout life. They do not depend on diet and do not change from season to season. 

Who and when should think about this?

Knowing your genetic characteristics of vitamin absorption is not relevant for everyone and not always. But there are situations when it becomes practically important:

• Chronic fatigueeven with normal sleep and a balanced diet, when the tests remain “within normal limits”, it may be associated with genetic features of the metabolism of B vitamins and magnesium.

• Plant-based diet —vegetariansandveganA plant-based diet by definition limits the intake of B12, iron, zinc, calcium, iodine, and vitamin A in direct form. Genetic characteristics of absorption either exacerbate or mitigate these limitations.

• Pregnancy planning andreproductive age— the question of the form of folic acid (standard or methylated) is increasingly being asked by doctors themselves. The answer depends on the hereditary characteristics of methylation.(Hecker et al.,Cureus, 2025).

• Preventive strategyafter 30— Deficiencies develop gradually and can go unnoticed for years. Knowing the genetic characteristics of assimilation before symptoms appear means being able to adjust your strategy in advance.

• Systematictaking supplementswithout a clear understanding of whether this particular form and dosage is suitable - the genetic context allows us to move from "let's try this" to an informed decision together with a doctor.

Genetics is not a sentence

A tendency to have reduced absorption of a particular vitamin does not mean that a deficiency is inevitable. Nutrition, intestinal condition, stress level, physical activity - all this also affects the actual availability of nutrients. Genetics determines the predisposition, but not the result.

 A genetic test does not replace a blood test, does not replace a doctor, and does not automatically select supplements. It provides context, an understanding of how your assimilation system works at the DNA level. With this context, a conversation with a doctor about the form, dosage, and tactics of taking supplements becomes objective, not speculative. 

If you are curious about how your body absorbs specific vitamins and minerals at the genetic level,

→ learn about the genetic characteristics of the metabolism of 20+ nutrients 

 Briefly about the main thing

If supplements don’t work, it’s rarely because of the quality of the pill. There are several steps between the vitamin’s intake and its actual impact on cells, and each of them can be “slowed down” for genetic reasons. A blood test won’t show this: it records the level in the blood, not the efficiency of absorption. A genetic test provides a stable context over time about how your metabolism is structured. Together with your doctor, this data helps you formulate a strategy based on your biology, not on average recommendations.

Genetic test results are not a diagnosis and are not a substitute for medical advice. The Apixmed Prism report provides genetic context that complements your test results and helps you make nutritional and supplement decisions with your doctor.

Sources:

1. Madeo G et al. (2023). Nutrigenomics: SNPs Correlated to Lipid and Carbohydrate Metabolism. Clin Ter, 174(Suppl 2):200–208. https://doi.org/10.7417/CT.2023.2488

2. Suzuki M, Tomita M (2022). Genetic Variations of Vitamin A-Absorption and Storage-Related Genes, and Their Potential Contribution to Vitamin A Deficiency Risks Among Different Ethnic Groups. Front Nutr, 9:861619. https://doi.org/10.3389/fnut.2022.861619

3. Guéant JL, Guéant-Rodriguez RM, Alpers DH (2022). Vitamin B12 absorption and malabsorption. Vitam Horm, 119:241–274. https://doi.org/10.1016/bs.vh.2022.01.016

4. Hecker J, Layton R, Parker RW (2025). Adverse Effects of Excessive Folic Acid Consumption and Its Implications for Individuals With the MTHFR C677T Genotype. Cureus, e79374. https://doi.org/10.7759/cureus.79374

5. Yin J et al. (2023). Magnesium Status, Genetic Variants of TRPM6 and the Risk of Gestational Diabetes Mellitus in Chinese Pregnant Women. Mol Nutr Food Res, 67(22):e2200835. https://doi.org/10.1002/mnfr.202200835 

6. Valenzuela-Vallejo L et al. (2025). Nutrigenetics and metabolic syndrome: systematic review. Genes Nutr, 20:18. https://doi.org/10.1186/s12263-025-00777-6

7. Elangovan R, Baruteau J (2022). Inherited and acquired vitamin B12 deficiencies: Which administration route to choose for supplementation? Front Pharmacol, 13:972468. https://doi.org/10.3389/fphar.2022.972468