Real talk for just a moment… Most people don’t take supplements for fun. They take them to feel better.
Sharper focus. Calmer moods. Fewer flares. Better sleep. More energy. And hopefully through a more “natural” or “holistic” lens.
But what if your supplements are fine—and it’s your absorption strategy that’s off?
Something that I see all too often in clinical practice, is that marketing language and practitioners dictate to patients to “just keep taking it,” without being taught how to actually maximize what they’re taking.
But as a functional medicine practitioner, I know that form, synergy, and biology matter just as much as dosing and the product specs and fancy lingo.
In this post, I’ll share:
- Why “more” is not better when it comes to vitamins and supplements (and when it can even make things worse)
- The simple shifts (like food pairings, timing, and gut support) that can take your supplement stack from guesswork to results
If you’ve felt stuck in trial-and-error mode, let these evidence-backed strategies help you stop wasting money and leverage your efforts to feel better faster!
Does Timing Matter? How to Take Supplements for Maximum Absorption
You’ve chosen the right form. You’ve checked the dose. But if you’re taking your supplements at the wrong time, or with the wrong foods, you might still be accidentally limiting their effectiveness.
Supplement timing is one of the most overlooked (and fixable) factors influencing bioavailability. Even a high-quality product can fall short if it doesn’t have the conditions it needs to be absorbed properly.
Let’s break down how timing, food pairing, and sequencing can optimize your results.
Water-Soluble vs. Fat-Soluble Nutrients
Your body absorbs nutrients differently depending on their solubility, or “what substance they travel best in.”
Water-Soluble Nutrients:
These dissolve in water and are absorbed directly into the bloodstream (which is mostly water). They are not stored in the body and must be replenished regularly since they are filtered easily through the kidneys and you urinate anything that you’re not using out.
Water-soluble nutrients include:
- The B-complex vitamins
- Vitamin C
- Electrolytes like potassium, sodium, magnesium chloride
They are best taken on an empty stomach, typically in the morning or between meals. And you want to avoid taking all B vitamins too close to bedtime because they can be stimulating for some people.
Fat-Soluble Nutrients:
These require dietary fat and bile from the liver and gallbladder for optimal absorption. They are stored in your fat tissue and the liver, so dosage and timing matter because they can build up over time.
Fat-soluble nutrients include:
- Vitamins A, D, E, K
- Omega-3 fatty acids (EPA/DHA)
- CoQ10, curcumin, and some botanicals
They are best taken with a meal that contains fat, ideally lunch or dinner. There are some supplement technologies such as micellized or emulsified versions that can bypass this need, but pairing with food still improves consistency and predictability.
Supplements on Empty Stomach vs. With Food
Some supplements perform better when the stomach is empty and digestive enzymes are at rest. Others depend on food-stimulated processes like stomach acid or bile flow.
Take These on an Empty Stomach:
- Probiotics: ideally 30 minutes before a meal or 2 hours after
- B-complex and Vitamin C: for faster absorption
- Amino acids like L-tyrosine: often used for mood or thyroid support
Take These With Food:
- Fat-soluble vitamins (A, D, E, K)
- Magnesium (non-oxide forms): reduces GI upset
- Zinc and iron: may cause nausea if taken without food
- Digestive enzymes and bitters: right before or with meals
AM vs. PM Timing for Supplements: Setting Your Daily Rhythm
Some nutrients are more supportive in the morning to align with natural energy rhythms, while others help calm and restore at night.
Supplements Best Taken in the Morning:
- B-complex vitamins: supports energy metabolism and neurotransmitter production
- Adaptogens like rhodiola or ashwagandha (lower dose): balances cortisol early in the day
- Vitamin D3: pairs well with morning sun exposure for circadian alignment
Supplements Best Taken in the Evening:
- Magnesium glycinate or threonate: supports nervous system, sleep, and muscle relaxation
- GABA or L-theanine: if using for relaxation
- Ashwagandha (higher dose or calming formula): can help lower nighttime cortisol
Avoid These Common Conflicting Supplement Combinations
Taking multiple minerals at once can lead to competitive inhibition and noncompetitive inhibition, where nutrients block each other’s uptake through various means. Here’s a few combinations that have the potential to block each other:
- Iron + Calcium: calcium blocks iron absorption; space these by at least 2 hours
- Zinc + Magnesium: can compete at high doses; consider splitting AM/PM
- Iron + Zinc: same transporter, best not taken together unless in low doses
- High-dose fiber + supplements: fiber can bind minerals and reduce absorption
How Stress, Sleep, and Inflammation Block Supplement Absorption
You could be taking the best supplements money can buy—bioavailable, targeted, therapeutic—but if your body isn’t physiologically ready to receive them, they may not perform at their best! This reality shocks many and highlights the need for creating the right environment for healing in our lives as well, both internally and externally!
This is the functional medicine lens in action: absorption isn’t just about the gut. It’s about the whole system. Chronic stress, poor sleep, and underlying inflammation all interfere with the body’s ability to absorb, convert, and utilize nutrients effectively.
Let’s explore how these root-level imbalances impact bioavailability and why they’re essential to address in any smart supplement strategy.
Chronic Stress and Cortisol: The Bioavailability Disruptor
When you’re under prolonged stress, your body shifts into sympathetic dominance—the classic “fight or flight” state. While this response helps us survive short-term threats, long-term activation comes at a cost.
Here’s how elevated cortisol affects nutrient absorption:
- Reduces stomach acid (hypochlorhydria): making it harder to digest proteins and absorb minerals like iron, calcium, magnesium, and B12
- Slows peristalsis: leading to bloating, constipation, and poor enzymatic breakdown
- Increases intestinal permeability (“leaky gut”): which compromises nutrient uptake and triggers immune activation
- Shunts blood away from the GI tract: prioritizing muscles and brain over digestion
💡 Key nutrient losses under chronic stress:
- Magnesium: rapidly depleted due to its role in calming the nervous system
- B6 and B5: needed to produce cortisol, and often depleted during prolonged output
- Vitamin C: used up by adrenal glands at a faster rate
Even if your supplement protocol is well-designed, a stressed system may not process it efficiently.
Sleep Deprivation: The Silent Saboteur of Nutrient Uptake
Inadequate sleep doesn’t just leave you groggy. It alters digestion and cellular repair in ways that affect how nutrients are handled.
Poor sleep has been shown to:
- Reduce melatonin, which plays a role in mucosal immune integrity and gut health
- Increase cortisol the next day, compounding the effects on digestion mentioned above
- Decrease production of digestive enzymes, impairing absorption of proteins, fats, and fat-soluble vitamins
- Slow gut motility, increasing risk of imbalances and overgrowths in the gut
Additionally, sleep is when your body rebuilds neurotransmitters and tissues, processes that require important materials like magnesium, zinc, and amino acids. If sleep is disrupted, the demand for nutrients rises—but absorption often drops, creating a vicious cycle.
Chronic Inflammation: Nutrient Turnover and Cellular Resistance
Ongoing inflammation, whether from processed food, leaky gut, infections, or environmental exposures, puts a metabolic tax on the body.
What that looks like:
- Increased nutrient demand to support antioxidant defense and repair
- Loss of nutrients through leaky gut or diarrhea
- Reduced cellular sensitivity to nutrients like vitamin D, insulin, or thyroid hormone
- Glutathione depletion, requiring more support from selenium, glycine, B2, and NAC
In other words, inflammation doesn’t just cause discomfort. It burns through your nutrient reserves faster than usual.
Common signs this is happening:
- Needing more caffeine or sugar to function
- Worsening skin, joint, or gut issues despite “clean eating”
- Labs showing low or borderline nutrients even with supplementation
Functional Medicine Insight for Your Supplement Hacks:
Think of it this way:
“If digestion is a fire, stress and inflammation pour water on the flame. Even with the best fuel (supplements), you won’t get a strong burn unless you fix the flame.”
That’s why every smart supplement strategy must also support nervous system regulation, gut integrity, and restorative sleep—not just the pill box.
Ask Your Open-Minded Provider About These Functional Labs to Guide Supplements
These tests can be run every 6–12 months to track progress, uncover hidden blocks, and prevent long-term nutrient depletion. When building or reevaluating your supplement plan, consider asking your functional provider about:
- Micronutrient Panels (Hair, blood, etc.)
- Organic Acids Test (Urine)
- Advanced Functional Gut Health Test (Stool)
- DUTCH Test (for hormone and cortisol patterns)
- Genetic SNP Panel (MTHFR, COMT, GST, etc.)
Smarter Supplementation Starts with a Smarter Framework
If you’ve ever found yourself with a growing “green pharmacy” of pills and powders, unsure what’s helping and what’s just a habit, you’re not alone. I’ve taken some of my patients from 27 supplements in their stack down to 8-9 tops!
Supplement overwhelm is real. And in my approach to functional medicine, more isn’t better. Strategic is better.
To wrap up this “supplement hacks” post, I want to highlight why I created my 3Ts of Smart Supplementation. It’s a simple but powerful way to cut through the noise and use nutrients with precision: Targeted. Therapeutic. Temporary.
This approach helps us move beyond protocols and symptom-chasing and instead focus on what your body truly needs. And it’s all based on your objective lab data, history, and capacity to heal.
Rather than repeat the full exploration here, I’ve already outlined everything (with examples) in this blog post: How to Supplement Smarter: The 3Ts of Functional Medicine
The bottom line is that your supplement routine should feel intentional, not overwhelming.
And it should always support actual healing, not just add to the noise.
Your Body Wants to Heal. Let’s Help It Receive Supplements
You could be buying the best supplements on the market, but if your body isn’t absorbing them, they won’t do their job. Stress, poor sleep, gut inflammation, and mistimed dosing can all block the benefits of even the most therapeutic products.
Functional medicine asks: “Is your body ready to receive what you’re giving it?”
You don’t need more pills, you need more precision.
Let’s map it out together. Book a Health Clarity Consult to get the ball rolling to fine-tune your routine with support that fits your biology.
This is the last of my 3-part series on bioavailability. Check out the other two articles here:
Part 1: Bioavailability Explained: Why Your Supplements Might Not Be Working (And How to Fix It)
Part 2: 10 Supplement Mistakes to Avoid: From Expensive Urine to Effective Support
About the Author
Kenny Mittelstadt is an acupuncturist and functional health practitioner based in San Antonio, Texas. He is trained through the Institute for Functional Medicine and received both of his doctorate degrees with highest honors from Southern California University of Health Sciences. He focuses on empowering patients through creating opportunities for integrated understanding and personalized root-cause healing - starting with gut health and growing beyond!