How to get the most out of your diet and supplements
The body’s physiology is intricate and complex. Even when we eat a healthy diet, we may not always absorb or utilize all of the nutrients our body needs. This is why scientists who formulate nutrient supplements are obsessed with bioavailability, defined as the rate and extent to which the active ingredient is absorbed and becomes available at its site of action.[1],[2]
The efficiency with which the body absorbs nutrients, either from the diet or supplements, is critical when it comes to health effects. If only 10% of a particular nutrient is bioavailable, for example, we may be missing many of the benefits we hope to achieve. If we understand the factors that impact nutrient bioavailability, we can more intelligently select supplements to meet our needs.[3]
What determines nutrient bioavailability?
Chemical, biological, and physiological factors all influence nutrient bioavailability.[4] These factors include the chemical form of the nutrient, the level of gastric acidity, gut motility, the composition of the microbiota, and the presence of enhancers, inhibitors, or competitors of gut absorption. Bioavailability is also influenced by hormones, chronic and acute infections, gut inflammation, stress, genetic polymorphisms, disease processes, and a wide variety of medications.
The bioavailability of micronutrients, i.e. vitamins, minerals, and bioactive phytochemicals (flavonoids, polyphenols, and carotenoids), can vary widely depending on conditions.
Macronutrients – carbohydrates, proteins, and fats – are usually highly bioavailable, with more than 90% of the amount ingested being absorbed and utilized in the human body.[5] By contrast, the bioavailability of micronutrients, i.e. vitamins, minerals, and bioactive phytochemicals (flavonoids, polyphenols, and carotenoids), can vary widely depending on conditions. Let’s examine some of these effects for specific nutrients.
Some vitamers are more bioavailable than others
Vitamins often exist in different chemical forms (vitamers), some of which are more bioavailable than others. An example of this can be seen for vitamin D, a deficiency of which is becoming a worldwide health problem. Vitamin D supplementation is the best approach to maintain adequacy, but the form of vitamin D used for supplementation matters. If you examine supplement labels you may find one of two forms of vitamin D: ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3). So which form is best? Numerous studies have shown that vitamin D3 is far more effective than vitamin D2 at raising circulating levels of vitamin D and improving vitamin D status.[6],[7],[8]
Vitamin E is also not a single entity. The vitamin E family includes tocopherols (α-, β-, δ-, and γ-tocopherol) along with tocotrienols (α-, β-, δ-, and γ-tocotrienol) which activate distinct cellular pathways.[9],[10],[11],[12] While α-tocopherol has long been regarded as the dominant form of vitamin E, the tocotrienols recently have been shown to possess superior antioxidant and anti-inflammatory effects, especially with respect to maintaining healthy blood cholesterol levels and supporting bone and heart health.[13],[14],[15] This argues for supplementation with a mixture of tocopherols and tocotrienols as compared with α-tocopherol alone.
Low levels of vitamin K2 have been implicated in chronic age-related diseases such as cardiovascular diseases, osteoporosis and osteoarthritis.
Vitamin K, too, comes in different forms. Although vitamin K1 (phylloquinone) and vitamin K2 (menaquinone, which exists in several forms) have historically been grouped into the same category, these molecules have different absorption characteristics and tissue distributions. Vitamin K1 is preferentially retained in the liver to assist in carboxylation (activation) of blood clotting factors.[16] In contrast, vitamin K2, in particular long-chain derivatives such as menaquinone-7 (MK-7), are redistributed to the circulation and are available for other tissues.[16],[17],[18],[19] Low levels of vitamin K2 have been implicated in chronic age-related diseases such as cardiovascular diseases, osteoporosis and osteoarthritis, and vitamin K2 supplementation may reduce these risks.[20],[21],[22],[23]
Nutraceutical formulations affect bioavailability
Curcumin is poorly absorbed unless it is formulated in such a way as to disperse the lipophilic components.
Many nutraceuticals have intrinsically low bioavailability, unless they are combined with other substances that facilitate absorption of the active ingredient(s). This is particularly true for fat-soluble (lipophilic) substances, including polyphenols.[24] Curcumin is a good example: it is a polyphenol derived from the dietary spice turmeric, which has many promising health-promoting effects including anti-inflammatory and antioxidant properties.[25],[26] But curcumin is poorly absorbed unless it is formulated in such a way as to disperse the lipophilic components.[27],[28],[29],[30]
To address this problem, a variety of curcumin formulations have been developed and evaluated.[24],[28] Research suggests that the best bioavailability can be obtained with a molecular process that enhances the water dispersion of the fat-soluble ingredients.[31] Such a formulation was shown to yield six times higher absorption than the commonly used curcumin phytosome (a complex of curcumin with phospholipids), and 46 times greater absorption than unformulated curcumin, resulting in elevated serum concentrations that persisted over 12 hours.
Physiological influences on nutrient digestion
Due to the risk for nutrient insufficiency, individuals with digestive difficulties may benefit from multivitamin and mineral supplementation. In addition, supplemental digestive enzymes, bile acids, and probiotics, may facilitate digestion and improve nutrient status.
Many factors that impact digestion also affect bioavailability.[32],[33] For example, nutrient bioavailability may be compromised in individuals with pancreatic insufficiency, inflammatory bowel disease (IBD; including Crohn’s disease or ulcerative colitis), irritable bowel syndrome (IBS), celiac disease, cystic fibrosis, and gastrointestinal surgeries, including bariatric surgery.[34],[35] Micronutrient deficiencies occur in more than half of patients with IBD.[36] Deficiencies of iron, folic acid, selenium, zinc, and vitamins D, K, B1, B6, and B12 are particularly common.[36],[37],[38],[39]
Pancreatic insufficiency (PI) reduces the absorption of fat-soluble vitamins, namely vitamins A, D, E and K.[40] The absorption of these and other lipid-soluble nutrients requires the production of lipase by the pancreas, so low levels of pancreatic enzymes are associated with nutrient deficiencies.[41],[42],[43],[44] The most well-known cause of PI is chronic pancreatitis,[44] but PI can also occur in individuals with cystic fibrosis,[45] weight loss surgery,[46] IBS,[47] diabetes or metabolic syndrome,[48],[49] celiac disease,[50],[51] small intestinal bacterial overgrowth,[52] or IBD.[53],[54],[55]
In fact, PI may be more common than previously thought, even in individuals without a defined gastrointestinal condition.[56],[57],[58] Stress and advancing age are associated with impaired digestion and absorption due to inadequate production of digestive enzymes.[56],[59],[60],[61] About 20% of individuals over age 60 with no history of a gastrointestinal disorder or surgery have evidence of PI.[62] Symptoms of mild PI can include bloating, cramping, increased flatulence, and diarrhea, much like IBS, which is also associated with vitamin deficiencies.[63]
Due to the risk for nutrient insufficiency, individuals with digestive difficulties may benefit from multivitamin and mineral supplementation.[64],[65],[66] In addition, supplemental digestive enzymes,[67],[68],[69] bile acids,[68] and probiotics,[70] may facilitate digestion and improve nutrient status in many individuals with these conditions. Probiotic and prebiotic supplementation can aid in restoring the microbiota to a healthier state.[71],[72],[73] Along with other direct benefits, probiotics have been shown to increase vitamin D absorption and thereby reduce vitamin D deficiency.[74],[75],[76]
The absorptive capacity of the intestine declines with age, which affects the bioavailability of vitamin B12, calcium, vitamin D, and other micronutrients.[77],[78] The body’s ability to absorb certain vitamins and minerals depends on many factors including adequate levels of stomach acid. Hypochlorhydria, a condition of having lower levels of stomach acid than one should, is more common with increasing age.[79],[80] Low stomach acid can occur as a consequence of chronic atrophic autoimmune gastritis, Helicobacter pylori infection,[81],[82] or the use of acid-suppressing medications such as proton-pump inhibitors (PPIs; used to treat acid reflux and heartburn, discussed further below).[83] Low acid conditions are known to impair the release of protein-bound vitamin B12 contained in food,[84] and reduce the absorption of β-carotene, folate, iron, calcium, zinc, and vitamin D.[85],[86],[87],[88],[89],[90]
Medications that reduce nutrient bioavailability
The use of antibiotics disrupts the gut microbiota and increases the risk of nutrient insufficiency.
Last but not least, a plethora of different medications can reduce nutrient bioavailability. Some notorious examples include acid-suppressing medications, noted above, which are associated with multiple nutrient insufficiencies;[91],[92],[93] metformin, a diabetes drug, which can reduce levels of folic acid and vitamin B12;[92],[94] diuretics (water pills), which deplete the body of magnesium and other minerals;[95] and statins (cholesterol-lowering medicine), which reduce serum levels of coenzyme Q10 (CoQ10) and vitamin K2.[96],[97] The use of antibiotics disrupts the gut microbiota and increases the risk of nutrient insufficiency. Antibiotics are used to treat infections, but they also eliminate the healthy bacteria that play a key role in the absorption and metabolism of micronutrients.[98],[99],[100],[101],[102] Probiotics can help restore a more normal microbiota during and after antibiotic treatment.[103]
As many other medications can cause nutrient depletion, it may be helpful to consult a health professional to determine if a medication you take is putting you at risk. Read the literature that comes with your prescription, and look up more about the drug on a reliable website, such as the National Institutes of Health.
Summary
Chemical, biological, and physiological factors all influence nutrient bioavailability. If you take supplements, do some research to identify the most bioactive form of the nutrient, and choose a supplier whose formulations are backed by research. Individuals with digestive difficulties and/or taking medications may benefit from multivitamin and mineral supplementation to prevent insufficiencies. (Note: if you have a chronic digestive disorder, be sure to consult a health professional to identify the cause.) Supplemental digestive enzymes and bile acids can help support digestion and improve nutrient status in many individuals. Probiotic and prebiotic supplementation can aid in restoring the microbiota to a healthier state, which improves nutrient status and overall health.
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