Many people rely on nutritional supplements either to tackle a health problem or ensure they do not succumb to deficiencies that might create one. Taking supplements has remained fairly stable over the past few decades, with about 52 percent of American adults reporting taking supplements within the previous month for the years 2011 – 2012 based on data from NHANES (National Health and Nutrition Examination Survey). However, using multivitamin/multi-mineral varieties has decreased some over the past few years, with 31 percent of adults in the US taking multivitamin/multi-mineral supplements compared to 37 percent from 1999 – 2000.
Often, the best way to start to consume the necessary vitamins, minerals, antioxidants, and other nutrients is from whole foods in your diet. However, what happens when you cannot get sufficient levels through what you eat? If you are like most people, you turn to dietary supplements. From there, you can choose to purchase synthetic nutrients or natural ones derived from whole foods.
Many supplements with a whole-food base claim they are superior to the synthetic option. Is there really a difference, or is it just marketing nonsense? Let’s see what the literature has to say.
Synergy of Foods and Nutrients
Whole foods have the reputation of being superior to taking supplements in large part due to food synergy, or the beneficial relationship between food constituents. Specific vitamins and minerals interact with one another, some increasing the other’s effectiveness and others inhibiting it. There are also many phytochemicals that work together in ways that science is barely beginning to identify. Macronutrients also impact the absorption and use of certain nutrients, especially lipids in the lipid-soluble vitamins.
For example, one study found that consuming avocado increased the bioavailability of the provitamin-A carotenoids in tomato sauce and carrots. Using two separate studies, the researchers tested the impact of consuming avocado on the absorption of vitamin A as well as other carotenoids, vitamin E, and vitamin K. In one study, the test meal included a novel high-beta-carotene tomato sauce, and the other study used carrots. In both studies, the participants consumed the test meals with breakfast and then ate control meals with limited vitamin A and carotenoids at lunch.
Eating the avocado with the tomato sauce led to a 2.4-fold increase in the levels of beta-carotene and a 4.6-fold increase in AUC retinyl esters. For the meal containing the carrots, the avocado led to a 6.6-fold AUC increase in beta-carotene, a 4.8-fold AUC increase in alpha-carotene, and a 12.6-fold increase in AUC of retinyl esters compared to those who ate the same meal without the avocado. There was also a 15-fold increase in vitamin K. Those who consumed the avocado also experienced an increase in vitamin A conversion. When eating the tomato sauce meal, the mean conversion was 22 percent without the avocado and 33 percent with it. Most likely, this effect was due to the lipids in the avocado helping with the absorption of the carotenoid.
Another example comes from a review study looking at the health benefits of apples. The authors found that the phytochemicals in apples enhanced the overall antioxidant capacity of the fruit. Despite having only 5 mg of vitamin C, the phytochemicals worked synergistically to provide the equivalent of 1,500 mg of vitamin C in antioxidant activity.
Natural Forms or Biologically Active Options
In addition to food-sourced supplements, some arguments state that certain vitamins require a certain form, often described as a natural form or a biologically active version. One vitamin with some reports that the natural form might have more efficacy than the synthetic form is vitamin E. Many supplements use a synthetic form known as all-rac-alpha-tocopherol, which has eight possible stereoisomers. Natural vitamin E has 100 percent of the RRR-alpha-tocopherol stereoisomer. Studies have found that the RRR-alpha-tocopherol stereoisomer is more efficiently absorbed, making it more bioavailable.
In one study that looked at data from the Irish National Adult Nutrition Survey (NANS) 2008 –2010, which was a cross-sectional dietary survey, the researchers compared the total vitamin E intake between all-rac-alpha tocopherol and the RRR stereoisomer. When considering vitamin E intake from all sources, 100 percent of the participants met the recommended intake, which was set at 12 mg/day. After adjusting for the all-rac-alpha-tocopherol (or the synthetic supplemental form) through using a bioactivity ratio of 0.74 (all-rac to RRR), the percentage remained at 100 percent of those who met the intake, although when looking at just food sources, only 68.4 percent of women met the intake while men still met the RDA.
This study found that the plasma distribution differed based on what type of supplement the participants took. In supplement users using the high all-rac-alpha-tocopherol options, there was only 82 percent of RRR-alpha tocopherol in the blood, which was significantly lower than non-users and high-RRR users (these were at 91.5 percent and 93.1 percent respectively). For other stereoisomers, the RSS low and high all-rac supplements users had higher percentages than those who took the RRR supplement. High all-rac supplement users also had a significantly higher percentage of the RS isomer. There was no significant difference in the 2S-steroisomers.
One study comparing all-rac-alpha tocopherol with RRR, or natural vitamin E, in nursing mothers found that both forms of the supplement increased the concentration of the vitamin in the mother’s colostrum, but the natural form was more effective at the task. In a double-blind, randomized control study, women were divided into three groups: a control group that did not take any treatment, a group taking natural RRR, and one taking synthetic all-rac. Blood and milk colostrum were collected and screened for vitamin E levels. There was no significant difference in the serum levels of alpha-TOH in all three groups of the study, and none had a deficiency of the vitamin. When looking at the alpha-TOH concentrations at 0 and 24 hours, the women who had no treatment had similar concentrations for both. The supplemented groups both exhibited an increase, with those taking the natural version having a 57.6 percent increase compared to a 39 percent increase in the synthetic group, which was statistically significant. Additionally, those who took the natural supplement had an average of 49.6 percent higher concentration of alpha-TOH in their colostrum compared to the synthetic. There was no correlation between serum levels and milk levels.
Another common vitamin with synthetic versus natural forms is vitamin K. Traditionally, vitamin K supplements used a synthetic version known as K1, but it has become more common to find the natural menaquinone-7, or MK-7. One study compared the absorption and efficacy of MK-7 and K1. Participants, who were healthy men and women between the ages of 25 and 35, took either vitamin K1 or MK-7 once a day at either breakfast or dinner. They also did not consume vitamin K-rich foods.
There were four different studies: a bioavailability study that included an oil intake, a dose-response relation, prolonged intake looking at osteocalcin carboxylation, and the impact on oral anticoagulants. Although both had similar absorption levels, the MK-7 had a much longer half-life, which allowed for more stable levels in the blood and a higher accumulation after taking for a period of time. This accumulation could cause issues if it reaches toxicity levels. The researchers found that when taking a vitamin K supplement daily, just 25 ug/day of MK-7 is more efficacious than 100 ug/day of K1, thanks to the longer half-life and subsequent accumulation. This also led to a more complete carboxylation of osteocalcin. MK-7 also had a stronger impact on anticoagulants, demonstrating a potential for more harm.
Natural Versus Synthetic Versions of Nutrients
There are limited studies comparing whole-food based and synthetic vitamins. One study looked at a novel plant-based calcium supplement and compared its impact on human osteoblast cells with two commonly used calcium salts. The plant-based calcium, AlgaeCal, was sourced from South American marine algae and contained 73 trace minerals in total, of which 28 to 31 percent of it is calcium and 2 to 4 percent is magnesium. The other calcium varieties were calcium carbonate and calcium citrate.
This was a cell study, and the osteoblast cells were treated with the AlgaeCal, calcium carbonate, and calcium citrate with and without vitamin D3 added. There was a significantly higher level of osteoblast activity compared to the control, the calcium carbonate, and the calcium citrate. There was also an increase in the calcium deposition, or mineralization, in those treated with the AlgaeCal compared to the control, calcium carbonate, and calcium citrate, including with the addition of vitamin D3. As this is a cell study, it does not mean that the same findings would take place in a person. Additionally, some of the efficacy of the supplement might come from its inclusion of other bone-benefiting minerals rather than that it comes from a more natural source.
In a mouse study, researchers compared magnesium and calcium from seaweed to synthetic versions (calcium carbonate and magnesium oxide). The rats were divided into four groups: sham-operated group, ovariectomized group, ovariectomized with synthetic calcium and magnesium, and ovariectomized with seaweed minerals. The seaweed contained 33 percent calcium and 3.2 percent magnesium along with other trace minerals, including selenium, iron, phosphate, boron, and manganese. The researchers found a similar intestinal absorption of the calcium. However, the seaweed calcium extract increased the strength and bone mineral density of the femoral bone in the rats.
Lycopene has been shown to have an inverse relationship with cardiovascular disease risk. In one review article comparing studies looking at lycopene supplements on CVD risk factors with a diet rich in tomatoes (a rich source of lycopene), the researchers found a modest benefit to tomatoes over lycopene supplements in terms of oxidized LDL in healthy, non-smoking individuals. There was no improvement in AOX results, a marker for antioxidant capacity, in studies on lycopene supplementation, while two out of 10 studies on tomatoes did show some improvement. A few studies showed some promise in preventing oxidative damage with lycopene supplements, but 10 of 17 found tomatoes to be effective in decreasing lipid peroxidation and other markers of oxidative stress, showing more data supporting tomatoes over lycopene supplements.
When looking at inflammation, several studies showed both lycopene and tomato products effectively reducing inflammatory markers, including CRP. However, there was some inconsistency with both. Both supplements and tomato products showed promise for reducing blood pressure. The researchers concluded that there was more evidence for consuming tomato rather than taking lycopene supplements, especially in regards to LDL oxidation and oxidative damage. However, there was some evidence indicating lycopene supplementation might be favorable for lowering blood pressure in hypertensive individuals. There is modest support for tomatoes rather than lycopene supplements to improve lipid metabolism. Tomatoes might have come out ahead, but there are promising findings for lycopene supplements as well, and the need for more targeted studies.
A systematic review looked at studies comparing synthetic and natural vitamin C. Some animal studies did demonstrate a significant increase in absorption and vitamin C level in the organs with natural vitamin C compared to synthetic options. Some studies demonstrated no difference, but for one notable study, the explanation was that the acerola cherry preparation ended up with almost no flavonoids due to the dilution and other extract preparation.
Additionally, this study compared this vitamin C fruit extract with blackcurrant juice. In the same review, the researchers found that in human studies, there was little difference in the urine and/or plasma bioavailability of vitamin C after taking synthetic supplements or from fruits, fruit juices, and vegetables. Studies also found comparable bioavailability between synthetic and natural forms of vitamin C.
In a randomized, steady-state study in 36 young, non-smoking adult males, the researchers found no significant differences in the bioavailability of the vitamin C. The researchers compared consuming a half of a gold kiwifruit or 50 mg of vitamin C in a chewable tablet over a period of six weeks. Both groups experienced an increase in plasma, skeletal muscle tissue, and leukocytes vitamin C levels during the six weeks of the test. However, there was no significant difference between the two groups, and the same was for urinary and seminal levels of vitamin C. Thus, both seemed to work just as well.
In one study on lactating women, the researchers found that the vitamin C from foods was better absorbed compared to that from supplements, and it thereby passed into the breast milk more efficiently.
Conclusion: A Need for More Studies
With all of the health benefits of eating whole foods, it intuitively feels as though supplements made from whole foods would have greater benefits than synthetic versions. There is limited evidence proving this theory, however. Some promising studies suggest it might be likely that this is the case, but it is too soon to make a definitive statement. And there is some evidence pointing to certain versions of vitamins and minerals having a better efficacy, such as the natural forms of vitamins E, K, D.
It is also important to remember that most supplement brands that start with whole foods also execute a certain amount of processing to increase the amounts of vitamins and minerals and to standardize dosing, which might lead to some of the other benefits of the foods (such as certain phytochemicals) not remaining in sufficient amounts to work synergistically in the same way as they do when you eat the whole foods. Thus, even if you choose whole-food supplements, you are still not consuming whole foods.