The First & Foremost Whitepaper: Bioavailability

Nov 18, 2022 | BY First & Foremost Clinical Team

The First & Foremost Whitepaper: Bioavailability



By Sarah Pettry, MS, RDN 

May 2022

Executive Summary:

This whitepaper introduces the science behind the concept of bioavailability, a measure of nutrient absorption. Bioavailability is impacted by numerous factors, which we explain here. Our deep research of bioavailability informed the formulation for First & Foremost, a dietitian-designed supplement program that provides the right nutrients (26 essential vitamins & minerals) in the right dosage at the right time.

Table of Contents:

1. Introduction

Amid a massive supplement market, no one seemed to get the basics — the nutrition — right. This was our priority in developing First & Foremost. We hold science and efficacy to the highest standard, and we are continuously researching and updating our formula to provide the best formulation, backed by the latest research.

As dietitians, we know that consuming something doesn’t mean you absorb all of the nutrients — and the benefits — therein. The impact of the nutrient content of vitamins and minerals within foods depends on the amount consumed, but also how much is really absorbed and used within the body. The amount of a nutrient available for absorption is defined as its bioavailability, which is a complex metric to quantify because it relies on many factors, both before consumption and within the body. 

Through the food production processes, from seed to harvest, washing, transporting, storing, prepping, cooking, eating, and lastly, during digestion, the nature of a food’s nutrient composition can evolve, thus affecting its nutritional benefit to the human body.

2. What Is Bioavailability? 

Bioavailability is the degree to which a nutrient that is consumed is absorbed and used within the body. Because absorption is not 100%, it is difficult to meet the recommended amounts of all essential nutrients each and every day solely from consuming foods. The bioavailability of your nutrient intake is important to consider because it affects your body’s absorption, utilization, storage, and excretion of nutrients.

The key factors impacting the bioavailability include: 

  • Efficiency of digestion and time of transit through the GI tract. 
  • Previous nutrient intake and nutrition status. 
  • Method of food preparation (raw, cooked, or processed). 
  • Source of the nutrient (synthetic, fortified, or naturally occurring). 
  • Other nutrients consumed at the same time, which may positively or negatively impact absorption.

3. Absorption of Vitamins Affected by Solubility of Nutrient 

As our focus at First & Foremost is on micronutrients, so too is this discussion. Vitamin absorption from food is easily affected by environmental and digestive factors. The vitamin content of food can be destroyed by oxidation, degradation, washing, cooking, and more. The solubility of vitamins also affects their absorption, transport, storage and excretion in the body. 

3a. Water & Fat-Soluble Vitamins

There are two types of vitamins: water-soluble and fat-soluble. Water-soluble vitamins are absorbed into portal blood, thus making them easily absorbed into the tissues of the body and metabolized more quickly than fat-soluble vitamins. 

Fat-soluble vitamins dissolve in fat — they are absorbed by fat globules within the body and carried throughout the bloodstream (they enter the lymphatic system as part of a chylomicron). These two vitamin types behave differently, and they function differently when your body needs them. 

Most of the time, water-soluble vitamins are excreted in the urine when plasma levels exceed the renal thresholds — they are not stored in large quantities in the tissues. Fat-soluble vitamins are stored in greater quantities in body tissues, mainly the liver, adipose and cell membranes. The amount stored varies widely on the type of fat-soluble vitamin. 

Water-soluble vitamins are absorbed directly into the blood from ingestion. As water-soluble vitamins circulate freely within the water-filled compartments of the body, the kidneys monitor the blood flowing through them, removing the small excesses through the urine — there is little buildup of water-soluble vitamins in the body. Therefore, a large excess of certain water-soluble vitamins can potentially overwhelm these systems, putting unnecessary strain on your kidneys, liver, and even causing irreversible nerve damage. Meanwhile, fat-soluble vitamins are held in the fatty tissues and liver until needed, and because they accumulate when consumed in excess, they are more likely to reach toxic/harmful levels.


 Water-Soluble Vitamins

Fat Soluble Vitamins


Vitamin A


Vitamin D


Vitamin E


Vitamin K

Pantothenic Acid


Vitamin B6

Vitamin B12

Vitamin C


3b. Minerals

Minerals are not as sensitive in their handling as they are not destroyed by heat, air, acid or mixing. However, they can be lost when leached into cooking water — your drain, not your body, gets those minerals. Within the body, mineral bioavailability is affected by two things: 1) minerals compete with one another for absorption and transport within the body, and 2) some minerals create insoluble complexes that are not absorbed, but excreted. 

Some minerals, like potassium, are easily absorbed into the blood, transported freely, and excreted by the kidneys. Other minerals, such as calcium, act more like fat-soluble vitamins in that they require help for absorption and transportation within the blood. The bioavailability of minerals can be reduced by some foods containing binders like phytates and oxalates (coffee, beans, berries, seeds, nuts, grains, and more), which can prevent their absorption and cause them to be excreted from the body. 

4. Synergistic Nutrients

We designed First & Foremost with nutrition science at the forefront to provide you with a healthy foundation of essential vitamins and minerals. When determining how much of each nutrient to include, we focused on bioavailability — that is, how much of the nutrient actually gets absorbed, and what is the circumstance in which it is best absorbed. Some nutrients work together to function in the body and need each other to perform specific tasks, so we paired these nutrients for optimal effect in your body. 

This approach highlights the reason we provide a complete slate of 26 essential nutrients. Certain nutrients should be consumed together, but there are also nutrients that need to be present within the body together (especially because different nutrients are stored differently, another factor that informed our formulation). Taking enough of a nutrient doesn’t necessarily mean you get enough if you’re not also regularly consuming its partner nutrients. For instance, you can take vitamin C, but if you don’t have enough zinc, your vitamin C won’t be effective. Here are a few relationships that informed our nutrient groupings:

Vitamin B12 & Folate:

Vitamin B12 works closely with folate to help make red blood cells and to help iron work better in the body. They also work together to produce S-adenosylmethionine (SAMe), a compound important for mood and immunity.

Vitamin D & Calcium:

Vitamin D interacts with the parathyroid hormone to regulate calcium in the body and is also needed to promote absorption of calcium in the intestinal tract, both mechanisms help to strengthen the integrity of bones.

Vitamin D promotes calcium absorption in the gut and maintains adequate calcium and phosphate concentrations to enable normal mineralization of bone and to prevent hypocalcemic tetany.

Iron & Vitamin C:

Vitamin C's role in enhancing iron's absorption is through the role of reducing ferric iron to the ferrous state. First & Foremost provides our iron as Iron Bisglycinate Chelate, which is iron already in the ferrous state. Therefore, vitamin C is not needed with iron (though we do include vitamin C in the evening, as it plays an important role in immunity).

5. Antagonistic Nutrients 

While there are nutrients that work together in codependent relationships, there are also several antagonistic nutrient relationships. These dynamics make it impossible to formulate an effective, comprehensive one-pill multivitamin. These antagonistic relationships need to be considered when formulating a supplement, which is why a day-parted formulation provides better bioavailability. 

Dayparting helps ensure that antagonistic nutrients are separate from one another, but also enables consumers to circumvent any dietary impact on bioavailability — certain foods can inhibit absorption, so it’s helpful for some nutrients to be taken with a meal and others to be taken between meals.

A few examples of antagonistic relationships are below: 


Several factors influence calcium absorption including Magnesium. Calcium and Magnesium compete with each other for intestinal absorption whenever excess of either is present in the gastrointestinal tract; which is why we broke the dosage of Calcium up into 3 occasions throughout the day. Absorption of Calcium from supplements is highest with doses of 500 mg or less. (2) Due to its weight and impact on bioavailability of other minerals, calcium is often omitted from supplements.


Excessive calcium and iron (25 mg or more) supplements are also known to inhibit zinc absorption. Calcium, zinc and manganese also interact with nonheme iron and may negatively affect absorption. First & Foremost recommends taking the Afternoon occasion, containing the day’s iron, on an empty stomach to avoid any nutrient interactions. If necessary to consume with a snack, choose a fruit or vegetable that is low in polyphenols.


Zinc diminishes calcium absorption, especially when the diet is low in calcium and contains an excess of zinc. This is why it is important to supplement with a complete nutrition versus spot treatment with one nutrient and not another.

Vitamin A, Vitamin E & Vitamin K

Vitamin E inhibits beta-carotene absorption and its metabolism in the intestine. In turn, excessive vitamin A and beta-carotene intake can inhibit vitamin E absorption. Vitamin E also impairs vitamin K absorption and its metabolism.

Oxalates, Phytates & Polyphenols

These food compounds interfere with many minerals’ absorption, including Magnesium, Calcium, Zinc, Manganese, Copper, Iron, Selenium, and Chromium. Polyphenols, or polyphenolic compounds, when consumed with a source of nonheme iron, can reduce iron absorption by over 50%. Coffee consumption, with or just after a meal, may reduce iron absorption by 40%. Phytic and oxalic acids complete with iron, as well as zinc and copper, among other minerals. Ingestion of oxalic acids (found in a variety of vegetables, fruits, nuts, and beverages) and phytic acid (found in whole-grain breads, seeds, and legumes) can decrease absorption of calcium; however, most individuals do not consume enough phytic acid and fiber to profoundly affect calcium absorption. (1)

6. Form

Nutrients behave differently in different forms — and that affects their bioavailability. We chose each nutrient’s highest quality form for better bioavailability. Here are some examples of why we chose a given nutrient form:

Chelated minerals to enhance absorption without nausea 

Chelators are small organic compounds that form a complex with a metal ion. For example, the iron chelate complex maintains solubility through absorption and the iron is loosely bonded, so the iron can be released at the enterocyte, which enhances absorption. (5)
We provide our iron in the form of iron bisglycinate chelate, which is iron in the ferrous state. Chelated ferrous iron is the most bioavailable form on the market, and as a bonus, it’s non-constipating. (6)

Calcium Carbonate and Calcium Citrate

The two most common forms of supplemental calcium are calcium carbonate and calcium citrate. Calcium carbonate is more soluble when taken with food by people with low levels of stomach acid, while calcium citrate is less dependent on stomach acid for absorption, so it can be consumed with or without food. Also, the absorption of calcium from supplements is highest with doses of 500 mg or less, so we split your RDA across three dayparts and leveraged both forms. (4)

Methylated Folate (5-Methyltetrahydrofolate)

Your body needs to methylate folic acid and folate for many bodily processes, but about 40% of people have the gene mutation (MTHFR polymorphism) that interferes in the methylation of folic acid. Therefore, we used methylated folate (measured to your full RDA) in our formulation to make the nutrient more bioavailable. Methylation can also positively influence mood stability, sleep and melatonin levels and detoxification. (7)

This holistic, comprehensive approach to diet and supplementation is essential for proper nutritional absorption and benefit. For more information on First & Foremost’s patent-pending formulation, please explore our other whitepaper.


  1. Advanced Nutrition and Human Metabolism; 7th edition; S. Gropper, J. Smith, T. Carr.
  2. S. Gabardi, K. Munz, C. Ulbricht. A Review of Dietary Supplement-Induced Renal Dysfunction. CJASN. 2007 Jul;2(4)757-765; DOI: 10.22.15/CJN.00500107.
  3. Bacharach R, Lowden M, Ahmed A. Pyridoxine Toxicity Small Fiber Neuropathy With Dysautonomia: A Case Report. J Clin Neuromuscul Dis. 2017;19(1):43-46. doi:10.1097/CND.0000000000000172.
  4. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US); 1997.
  5. Advanced Nutrition and Human Metabolism; 7th edition; S. Gropper, J. Smith, T. Carr. Page 484.
  6. L ayrisse M, GarcĂ­a-Casal MN, Solano L, BarĂłn MA, Arguello F, Llovera D, RamĂ­rez J, Leets I, Tropper E. Iron bioavailability in humans from breakfasts enriched with iron bis-glycine chelate, phytates and polyphenols. J Nutr. 2000 Sep;130(9):2195-9. PubMed PMID: 10958812.