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Supplements to Take With and Without Food

Supplements to Take With and Without Food

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Guidelines for optimal absorption and benefit

“I think your love language is snacks,” my friend says after I greet her with a hug and a jar of homemade vegan coconut yogurt. “I think you’re right!” I laugh, and beckon her to open up the jar so we can have a nosh.

Later that month, I undergo a small medical procedure. My doctor suggests I take proteolytic enzymes three times a day, on an empty stomach to help speed up my recovery.

Three times a day!? On an empty stomach!? As if my stomach is empty three times a day! And that’s when I realized, Wow, I really do love healthy food. That was both a good opportunity for me to bring awareness to gusto for snacks, and as well as to brush up on which supplements are best taken away from – or with – meals.

Proteolytic enzymes

To aid in my recovery, I turned to natural constituents like bromelain and papain to mitigate inflammation.[1] To ensure the systemic action of the enzymes, I quit snacking and took these products away from food, on an empty stomach.[2] Although there’s no harm in taking these types of enzymes with food, the enzymes will likely get put to work in digesting the food instead of tackling the mediators of inflammation, thereby somewhat defeating the purpose of taking them.

Other enzymes, however, are best taken with meals, specifically for the purpose of aiding in digestion. These so-called digestive enzymes – such as papain from papaya, amylase, and protease – can be handy for those with sensitive stomachs, bloating, belching, and irritable bowel syndrome (IBS), among other conditions.[3]


It’s no wonder that iron supplements can be found in just about any pharmacy or supermarket: iron deficiency anemia is the most prevalent micronutrient deficiency related disease worldwide.[4] And it’s very important to treat: many doctors have observed that no matter how sophisticated a treatment plan may be, it will only moderately help a patient if they have an uncorrected iron deficiency.[5],[6]

Thankfully, iron is available to us in a variety of foods, as well as in nutritional supplements. Daily iron supplementation effectively treats anemia and iron deficiency and, can also reduce fatigue and even improve exercise performance in those with deficiency.[7]

The absorption of the type of iron found in vegetarian foods and most iron supplements is greatly influenced by meal composition.

There are two primary forms of iron: heme and non-heme. Heme iron, which is found in animal products, is well absorbed regardless of what other foods are eaten in the same meal. Non-heme iron, on the other hand, is the form of iron found in vegetarian foods and most iron supplements and its bioavailability is greatly influenced by meal composition.[8]

Caffeine, such as that found in coffee and black tea, has been shown to limit iron absorption. Fiber-rich foods too, such as whole grains, can compromise the absorbability of iron from plant-based foods and supplements.[9]

Some studies have shown that calcium – both in the form of calcium salts or in dairy products – inhibits non-heme iron absorption.[10] Other studies, however, have shown these effects to be overstated, or of short duration only.[11],[12] Nevertheless, it’s probably still a good idea to play it safe and take iron supplements away from milk, calcium products, and antacids (which typically contain calcium).

Medications that reduce stomach acid levels (e.g., antacids and proton pump inhibitors) can also impair absorption of iron, as well as the absorption of other essential minerals such as calcium and vitamin B12.[13] In fact, many sources advise patients to take iron supplements away from food altogether, so that the acidic milieu of the stomach can better break down the non-heme iron, which is then absorbed in the first part of the small intestine.

The absorption of iron from a plant-based meal is directly proportional to the amount of vitamin C present in said meal.

Some people experience nausea, diarrhea, or belly aches after taking iron on an empty stomach, and are thus better served by eating a small amount of food with their supplements. Foods rich in vitamin C – like strawberries, citrus, cantaloupe, and currants – might be particularly good choices, as ascorbic acid (vitamin C) highly enhances non-heme iron absorption in the gut. In fact, the absorption of iron from a plant-based meal is directly proportional to the amount of vitamin C present in said meal. Vitamin C can even override the inhibiting effects of calcium. It does this by bonding to the iron at acidic pH levels; this bond then dissolves upon reaching the alkaline pH of the duodenum (first part of the small intestine), where the iron is then absorbed into the body.[14] Humans are among the only species that cannot produce vitamin C in their bodies.[15] That’s why many practitioners recommend taking a vitamin C supplement at the same time as an iron pill, and/or washing it all down with a glass of orange juice.


There has been a recent explosion in our understanding of the role of the bacteria, viruses, and fungi collected on and within our bodies – collectively known as the microbiome. Probiotic supplements are now understood to play a beneficial role in a variety of body systems, from digestive health, to heart health, to immune system integrity. Many sources agree that probiotic supplements are safe for all ages, including infants, children, adults, and elders (though caution is advised in the immunologically vulnerable, such as those with HIV/AIDS and those undergoing chemotherapy).[16]

What providers often disagree upon, however, is whether to take probiotics with or away from food.

In a study in Beneficial Microbes, researchers set out to clarify when to best take probiotics.[17] The four different probiotic strains they examined included two lactobacilli (Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011), Bifidobacterium longum R0175 and Saccharomyces cerevisiae var. boulardii.

The researchers found that the Lactobacillus and Bifidobacterium probiotic strains survived in much higher numbers if taken within 30 minutes of starting a meal or with the meal rather than 30 minutes after a meal.

They also found the probiotic strains had the greatest survival when eaten with fat-containing foods: the survival in 1% milk and an oatmeal-with-milk mixture was significantly better than the survival when taken with apple juice or spring water. The authors therefore conclude: “Ideally, non-enteric coated bacterial probiotic products should be taken with or just prior to a meal containing some fats.”

(Curiously, the survival of Saccharomyces boulardii was affected neither by the timing nor the buffering capacity of the meal in this study.)

However, another study found that probiotics (Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536) caused positive changes in the gut microbiome regardless of whether or not they were taken with a meal.[18]

Probiotics must survive in the acidic environment of the stomach if they are to reach (and colonize) the small intestine.

Probiotics must survive in the acidic environment of the stomach if they are to reach (and colonize) the small intestine. Lactobacillus, Bifidobacterium, and Enterococci are understood to be more resistant to stomach acid than other types of bacteria.[19] In fact, most probiotic strains of Lactobacillus come from the human intestinal tract, so they’re considered inherently resistant to stomach acid.[20] L. rhamnosus GG in particular has been shown to survive passage through the gastrointestinal tract in both children and adults.[21]

It’s also a good idea to wash probiotic supplements down with filtered water, as the chlorine added to municipal water could harm or kill these “good bacteria.”

Vitamin D3

Vitamin D3 is a fat-soluble vitamin, meaning that it does not dissolve in water and is absorbed best into the bloodstream when paired with fat.[22] For this reason, it’s recommended to take vitamin D3 with some fat-containing foods, such as salmon, nuts and nut butters, olives and olive oil, and avocado.

According to a study of 17 people, taking vitamin D3 with the largest meal of the day increased vitamin D blood levels by about 50% after just two to three months.[23] Prior to the study period, participants had been taking the same dose of vitamin D, however, it was being consumed either away from food or with a small meal; thus, by taking it with the largest meal it could be concluded that absorption was significantly enhanced.

Vitamin D3 levels were observed to be 32% higher in those who took the supplement with a fat-heavy meal than in those who took it with a fat-free meal.

In another study of 50 older adults, vitamin D3 levels were observed to be 32% higher in those who took the supplement with a fat-heavy meal than in those who took it with a fat-free meal.[24] The authors conclude: “The presence of fat in a meal with which a vitamin D-3 supplement is taken significantly enhances absorption of the supplement.” Interestingly, it didn’t seem to matter whether the fat in the meal came from monounsaturated (MUFA) or polyunsaturated fatty acids (PUFA) – in this study both types of fatty acids enhanced vitamin D3 absorption.

Essential fatty acids

As the name implies, essential fatty acids, or EFAs, are fats. Specifically, they’re essential fatty acids – meaning we humans cannot synthesize them in the body and thus must get them from the diet. The two types of EFAs are based on linoleic acid (omega-6) and alpha-linolenic acid (omega-3): we need both types for health and survival.

Studies have shown that taking EFAs can help prevent and treat a number of diseases, from dementia,[25] to cardiovascular disease,[26] to diabetes,[27] to certain types of cancer.[28] EFA intake can even improve body composition, mental performance, and physical stamina.[29] It’s no wonder that the Mediterranean Diet, which is rich in healthy fats, has been associated with good health outcomes.[30]

Being that they are comprised of fat, much like vitamin D, EFAs seem to be most effective when taken alongside fat-containing foods.[31]


Astaxanthin has been shown to provide important health perks, acting as an anti-inflammatory, antioxidant, anti-cancer, and cardioprotective nutrient. Studies have also shown that astaxanthin supports long-term memory and may protect the brain against Alzheimer’s and Parkinson’s diseases.[32]

Astaxanthin, a member of the carotenoid family, also is a lipid-soluble molecule, meaning it dissolves in fat. Taking astaxanthin with food – fat-rich food, specifically – is thus the best way to capture the therapeutic potential of this nutrient. Absorption and retention of supplemental astaxanthin is much higher (the area under the curve being more than double) if taken immediately after meals rather than away from food.[33]

To eat or not to eat?

While many supplements and nutritional aids can be taken with or without food, we suggest the following:

  • Enzymes: with food for digestive support; away from food for anti-inflammatory action
  • Iron: with a little vitamin C, but taken away from food, or with a small amount of dairy free, caffeine-free food
  • Probiotics: with or without food, depending on the strain(s). The safest bet is probably within 30 minutes before or toward the beginning of a meal containing fat, as opposed to on a full stomach
  • Vitamin D3: with fat-containing food
  • Essential fatty acids: with fat-containing food
  • Astaxanthin: with fat-containing food
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The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.

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