Introduction: Why Supplements Don't Work?
Taking a handful of supplements every day, yet not seeing results? The problem may not lie in the quality of supplements, but in the state of your gut microbiome – a community of trillions of microorganisms in your digestive tract.
In your gut lives 10-100 trillion bacteria, which are not passive passengers. They actively participate in digestion, vitamin production, immune regulation and – crucially – in the absorption of nutrients and supplements.
Recent research shows something fascinating: gut microbiota may be responsible for why the same supplement works perfectly for one person, but not at all for another. It's not a matter of luck – it's a matter of your microbiome's health.
How Does the Microbiome Affect Supplement Absorption?
1. Biotransformation – changing chemical structure
Gut bacteria produce enzymes that humans don't possess. These enzymes can:
- Release active ingredients from their inactive forms
- Modify chemical structure of substances, increasing or decreasing their absorption
- Degrade substances before they get absorbed
Studies have shown that the microbiome can modify the structure of up to 271 different oral drugs through processes such as oxidation, reduction, or hydroxylation.
Example: Resveratrol (a popular antioxidant) is converted by gut bacteria into metabolites with varying biological activity. At the same time, resveratrol changes the composition of the microbiota, increasing the abundance of beneficial bacteria like Lactobacillus and Bifidobacterium.
2. Impact on transporters – absorption "gates"
Microbiota affects transport proteins in intestinal cells, which are responsible for substance absorption.
Animal studies have shown that:
- The bacterium Bacteroides thetaiotaomicron decreased the expression of protein pumping substances out of cells fourfold
- Lactobacillus murinus increased bioavailability of certain substances by lowering transporter expression
3. Production of short-chain fatty acids (SCFA)
This is the most important mechanism! SCFA – acetate, propionate, and butyrate – are produced from fiber fermentation by gut bacteria.
What do SCFAs do?
- Acidify the intestinal environment – lowered pH increases solubility and absorption of minerals (calcium, magnesium, iron, zinc)
- Are an energy source for intestinal cells – butyrate provides 70% of the energy needs of colonocytes
- Strengthen the intestinal barrier – increase expression of tight junction proteins
- Reduce inflammation – have anti-inflammatory effects
It's estimated that fermentation of 50-60g of carbohydrates daily generates approximately 500-600 mmol of SCFA, which represents about 10% of our daily energy requirement.
Leaky Gut Syndrome: The Main Enemy of Absorption
What is "leaky gut"?
Under normal conditions, the intestinal wall acts like a sieve – letting beneficial nutrients through, while blocking harmful substances (toxins, bacteria, undigested particles).
When tight junctions between epithelial cells weaken, microscopic "holes" form, through which unwanted substances leak into the bloodstream, triggering an inflammatory response.
Causes of leaky gut:
- Gut dysbiosis (imbalanced microbiome)
- Pro-inflammatory diet (sugar, trans fats, processed foods)
- Chronic stress
- Medications (NSAIDs, proton pump inhibitors, antibiotics)
- Alcohol
- Nutrient deficiencies (zinc, vitamin D, glutamine)
Effects on supplement absorption:
When the intestinal barrier is damaged:
- Transporter function is impaired
- Chronic inflammation decreases expression of digestive enzymes
- Absorption surface area decreases
- Pathogenic bacteria "steal" vitamins and minerals
Specific Examples: Supplements and Microbiome
B Vitamins
What studies say: Gut bacteria produce 40-65% of eight B vitamins. Species such as Bacteroides, Bifidobacterium, and Lactobacillus synthesize these vitamins from scratch.
Key note: Vitamins must be produced "before" their absorption site. Vitamin B12 is absorbed in the ileum, so large intestine bacteria producing B12 are unlikely to contribute to increasing its bioavailability for the host.
Iron
Iron is a special case – its supplementation can have both positive and negative effects:
- Positive: Correcting deficiencies improves immune function
- Negative: Excess iron promotes growth of pathogens (e.g., E. coli)
Studies have shown that high-dose iron (6.4 mg/day) significantly decreased the abundance of beneficial Bifidobacterium compared to a lower dose (1.2 mg/day).
Lesson: Iron supplementation should be carefully dosed, especially in people with gut issues.
Zinc
Zinc is essential for maintaining intestinal barrier integrity.
Studies show:
- Zinc deficiency alters microbiota structure, leading to decreased diversity and increased inflammation
- A randomized study in patients with Crohn's disease showed that zinc supplementation helped "seal" leaky gut
- Zinc-carnosine in a study showed impressive improvement in gut integrity after just 4 weeks
Recommended dosage: 15-30 mg daily (preferably in chelate or carnosine form).
Polyphenols (resveratrol, quercetin, curcumin)
Polyphenols have low bioavailability in unchanged form, but microbiota converts them into more bioactive metabolites.
Studies show that phenolic phytochemicals with low bioavailability can reduce levels of harmful compounds mainly through gut microbiota remodeling.
How to Fix the Microbiome and Improve Absorption?
1. Prebiotics: food for good bacteria
Prebiotics are indigestible dietary fibers that stimulate the growth of beneficial bacteria.
Best sources:
- Inulin: artichokes, garlic, leeks, onions (5-10g daily)
- FOS: bananas, garlic, asparagus (2-10g daily)
-
Resistant starch: cooled potatoes, green bananas,
beans (15-30g daily)
A 2018 study showed that fiber consumption inhibited growth of harmful bacteria and reduced levels of bacterial toxins in patients with type 2 diabetes.
2. Probiotics: live beneficial bacteria
Lactobacillus rhamnosus GG:
- Strengthens intestinal mucosa protection
- Reduces inflammation
- Dosage: minimum 10 billion CFU
Bifidobacterium longum:
- Protects against pathogens
- Produces acetate and lactate
- Supports intestinal barrier
Saccharomyces boulardii:
- Probiotic yeast
- Prevents Candida overgrowth
- Helpful in diarrhea
Recommendations:
- Multi-strain formulas (10-50 billion CFU)
- Take on an empty stomach or with a light meal
- Combine with prebiotics (synbiotics)
3. Supplements repairing the intestinal barrier
L-Glutamine:
- Main energy source for intestinal cells
- Repairs tight junctions
- Dosage: 5-15g daily
Zinc-carnosine:
- Promotes repair of damaged epithelial cells
- Dosage: 75mg twice daily
Butyrate:
- Supports colonocyte health
- Has anti-inflammatory effects
- Dosage: 150-300mg daily
Omega-3 (EPA and DHA):
- Reduces mucosal inflammation
- Supports barrier integrity
- Dosage: 2-3g daily
Quercetin:
- Reduces intestinal permeability
- Protects against oxidative stress
- Dosage: 500-1000mg daily
4. Diet supporting a healthy microbiome
What to eat:
- Fermented foods: Sauerkraut, kimchi, kefir, natural yogurt, kombucha → Provide live probiotics and postbiotics
- Fiber – minimum 30g daily: Vegetables, berries, legumes, whole grains, nuts
- Polyphenols: Green tea, dark chocolate (>70%), berries, olive oil, turmeric
What to avoid:
- Sugar and artificial sweeteners – feed pathogens
- Processed foods – contain emulsifiers that damage the barrier
- Excess alcohol – directly damages intestinal cells
Lifestyle for Gut Health
Stress management
- Chronic stress alters microbiota composition and weakens the intestinal barrier. → Meditation, yoga, deep breathing (10-20 min daily)
Regular sleep
- Microbiota has its own circadian rhythm. Sleep disturbances lead to dysbiosis. → 7-9 hours of sleep, consistent schedule, limiting blue light in the evening
Regular physical activity
- Exercise increases microbiota diversity and SCFA production. → 150 minutes of moderate activity weekly
Caution with antibiotics
- Antibiotics destroy the microbiome – effects can last months. → If you must take them: add probiotics (2-3h after antibiotic), increase fiber.
- A 2023 study in Nature Communications showed that fiber supplementation protects against antibiotic-induced dysbiosis
Common Mistakes in Supplementation
Mistake #1: Supplements without gut repair
Problem: Damaged barrier = poor absorption
Solution:
First repair the gut, then optimize supplementation
Mistake #2: Too high probiotic doses at the start
Problem: People with SIBO may poorly tolerate high
doses
Solution:
Start with 5-10
billion CFU and gradually increase
Mistake #3: Ignoring prebiotics
Problem: Probiotics without prebiotics may not colonize the gut
Solution:
Always combine probiotics with prebiotics
Mistake #4: Lack of patience
Problem: Microbiome repair takes time
Solution: Minimum 3-6
months of consistent action
Mistake #5: Forgetting about diet
Problem: Supplements won't replace a bad diet
Solution: 80%
of success is diet and lifestyle, 20% is supplementation
Summary: The Key to Effective Supplementation
A healthy gut microbiome and tight intestinal barrier are the foundation of effective supplementation. Here are the most important conclusions:
- Microbiome directly affects supplement bioavailability through biotransformation, transporter modulation, SCFA production, and inflammation regulation
- Leaky gut syndrome dramatically reduces absorption of vitamins, minerals, and other nutrients
- Gut repair should be a priority – first repair the barrier, then optimize supplementation
- Key supplements for gut health:
-
- Multi-strain probiotics (25-50 billion CFU)
- Prebiotics (5-10g daily)
- L-glutamine (5-15g daily)
- Zinc-carnosine (150mg daily)
- Butyrate (150-300mg daily)
- Omega-3 (2-3g daily)
- Diet is the foundation – minimum 30g of fiber daily, fermented foods, polyphenols, avoiding sugar
- Lifestyle matters – stress management, 7-9h of sleep, regular physical activity
- Patience is key – microbiome repair requires 3-6 months of consistent action
Remember: There's no magic pill. Healthy gut is the result of a holistic approach combining proper diet, supplementation, stress management, and healthy lifestyle. If you invest in your gut health, it will invest in your overall health – better energy, stronger immunity, and optimal supplementation effectiveness.
Bibliography and sources:
Studies on microbiome and bioavailability:
- Barone, M., Turroni, S., Rampelli, S., et al. (2022). "Gut microbiome–micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins?" BioFactors 48(2):307-314. DOI: 10.1002/biof.1835
- Das, P., Babaei, P., Nielsen, J. (2019). "Metagenomic analysis of microbe-mediated vitamin metabolism in the human gut microbiome." BMC Genomics 20:208. DOI: 10.1186/s12864-019-5591-7
- Zhang, X., Han, Y., Huang, W., et al. (2021). "The influence of the gut microbiota on the bioavailability of oral drugs." Acta Pharmaceutica Sinica B 11(7):1789-1812. DOI: 10.1016/j.apsb.2020.09.013
- Li, L., Somerset, S. (2018). "Bioavailability Based on the Gut Microbiota: a New Perspective." Microbiology and Molecular Biology Reviews 82(4):e00016-18. DOI: 10.1128/MMBR.00016-18
- Spanogiannopoulos, P., Bess, E.N., Carmody, R.N., Turnbaugh, P.J. (2016). "The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism." Nature Reviews Microbiology 14:273-287. DOI: 10.1038/nrmicro.2016.17
Studies on SCFA:
- Koh, A., De Vadder, F., Kovatcheva-Datchary, P., Bäckhed, F. (2016). "From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites." Cell 165(6):1332-1345. DOI: 10.1016/j.cell.2016.05.041
- den Besten, G., van Eunen, K., Groen, A.K., et al. (2013). "The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism." Journal of Lipid Research 54(9):2325-2340. DOI: 10.1194/jlr.R036012
- Silva, Y.P., Bernardi, A., Frozza, R.L. (2020). "The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication." Frontiers in Endocrinology 11:25. DOI: 10.3389/fendo.2020.00025
- Oliphant, K., Allen-Vercoe, E. (2024). "Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications." Life 14(5):559. DOI: 10.3390/life14050559
Studies on intestinal barrier:
- Camilleri, M. (2019). "Leaky gut: mechanisms, measurement and clinical implications in humans." Gut 68(8):1516-1526. DOI: 10.1136/gutjnl-2019-318427
- Bischoff, S.C., Barbara, G., Buurman, W., et al. (2014). "Intestinal permeability – a new target for disease prevention and therapy." BMC Gastroenterology 14:189. DOI: 10.1186/s12876-014-0189-7
- Martínez Leo, E.E., Segura Campos, M.R. (2023). "Leaky Gut and the Ingredients That Help Treat It: A Review." Molecules 28(2):619. DOI: 10.3390/molecules28020619
Studies on probiotics and prebiotics:
- Hill, C., Guarner, F., Reid, G., et al. (2014). "Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic." Nature Reviews Gastroenterology & Hepatology 11:506-514. DOI: 10.1038/nrgastro.2014.66
- Gibson, G.R., Hutkins, R., Sanders, M.E., et al. (2017). "Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics." Nature Reviews Gastroenterology & Hepatology 14:491-502. DOI: 10.1038/nrgastro.2017.75
- Korry, B.J., Cabral, D.J., Belenky, P. (2023). "Fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential." Nature Communications 14:5161. DOI: 10.1038/s41467-023-40553-x
Studies on specific supplements:
- Sturniolo, G.C., Di Leo, V., Ferronato, A., et al. (2001). "Zinc supplementation tightens 'leaky gut' in Crohn's disease." Inflammatory Bowel Diseases 7(2):94-98. DOI: 10.1097/00054725-200105000-00003
- Benjamin, J., Makharia, G., Ahuja, V., et al. (2012). "Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn's disease: a randomized controlled trial." Digestive Diseases and Sciences 57(4):1000-1012. DOI: 10.1007/s10620-011-1947-9
- Zhao, L., Zhang, F., Ding, X., et al. (2018). "Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes." Science 359(6380):1151-1156. DOI: 10.1126/science.aao5774
- Kumar Singh, A., Cabral, C., Kumar, R., et al. (2019). "Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency." Nutrients 11(9):2216. DOI: 10.3390/nu11092216
- Rinninella, E., Raoul, P., Cintoni, M., et al. (2019). "What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases." Microorganisms 7(1):14. DOI: 10.3390/microorganisms7010014