What to combine Vitamin C with

Vitamin C is rarely taken in isolation: it is part of multivitamins, "immune" complexes, collagen drinks and iron supplements. Some of these combinations have a clear biochemical rationale, others are rather a matter of marketing. The editorial team has examined what vitamin C is really worth combining with, and what to be cautious about.

Vitamin C and iron

The best-substantiated combination is vitamin C with non-heme iron, that is, iron from plant foods and most supplements. Ascorbic acid reduces ferric iron to ferrous iron and forms a soluble complex with it that passes more easily through the intestinal wall. In addition, it partly neutralizes the action of absorption inhibitors — phytates and polyphenols.

The classic work of Hallberg and colleagues showed that adding vitamin C to food increases the absorption of non-heme iron in a dose-dependent way. The effect is especially noticeable in dishes with a lot of phytates — grains and legumes. For heme iron from meat, vitamin C is less important, because it is absorbed by a different route.

In practical terms this means: vegetarians, vegans and female athletes with low ferritin benefit from combining legumes, grains and leafy vegetables with sources of vitamin C — peppers, citrus fruits, kiwi, sauerkraut. Tea and coffee with such a meal, on the contrary, reduce iron absorption.

For iron tablets the picture is less clear-cut. The randomized study by Li and colleagues (2020) in patients with iron-deficiency anemia found no significant difference in the rise of hemoglobin and ferritin between taking iron with and without vitamin C. So adding vitamin C to an iron supplement is not harmful, but it is not mandatory either; the treatment regimen for anemia is determined by a doctor.

Collagen, gelatin and connective tissue

Vitamin C is a cofactor for the enzymes prolyl hydroxylase and lysyl hydroxylase, which modify amino acids in the collagen molecule. Without this modification, collagen fibers are unstable — that is why in scurvy the gums bleed and wounds heal poorly.

The combination of collagen or gelatin with vitamin C was tested in the study by Shaw and colleagues (2017). Participants received 5 or 15 g of gelatin with vitamin C (about 50 mg) an hour before a short jumping exercise. In the 15 g group, blood markers of collagen synthesis rose about twofold compared with placebo, and engineered ligaments grown on the participants' serum had better mechanical properties.

This is a small study, and it does not directly prove a reduction in injury risk. However, it provided a practical model that sports dietitians use in rehabilitation after tendon and ligament injuries: gelatin or collagen together with a small dose of vitamin C 30–60 minutes before the targeted exercise.

Megadoses are not needed for such a combination. The amount of vitamin C contained in a glass of orange juice or in a small tablet is enough. Most collagen products already contain vitamin C.

Vitamin E and other antioxidants

Vitamin C and vitamin E work in tandem: the fat-soluble tocopherol protects cell membranes from lipid peroxidation, while the water-soluble ascorbate regenerates oxidized tocopherol, restoring its activity. This "antioxidant hierarchy" is well described in the biochemical literature (Buettner, 1993).

In dietary amounts the combination of C and E is logical and safe — that is exactly how they are present in a diet with nuts, seeds, vegetables and fruit. The problem arises when both vitamins are taken in high doses every day during a training block.

The studies by Ristow and colleagues (2009) and Paulsen and colleagues (2014) showed that the combination of vitamin C (1000 mg) and vitamin E (in doses of hundreds of international units or milligrams) blunts some of the adaptations to training — increased insulin sensitivity and markers of mitochondrial biogenesis. In other words, it is precisely this popular pair, in high doses, that is most studied as a "brake" on adaptation.

Other antioxidants — polyphenols, alpha-lipoic acid, N-acetylcysteine — can also affect redox signaling in high doses. If you take several such supplements at once, take the total load into account.

Zinc, sports nutrition and other supplements

Vitamin C is often combined with zinc in "immune" complexes. Both nutrients are important for the immune system, and in cold studies each of them individually showed certain effects. However, there is little convincing data on synergy specifically in combination. The combination is safe as long as upper limits are observed: for zinc that is 40 mg per day according to the IOM and 25 mg according to EFSA.

No significant interactions of vitamin C with creatine, protein, BCAAs, caffeine and other popular sports supplements have been described. It can be added to the same shake or drink. One should only remember that ascorbic acid in solution gradually oxidizes, so it is better not to store ready-made drinks for long.

Vitamin D, magnesium and omega-3 acids also have no clinically significant interactions with vitamin C and can be taken together. A multivitamin complex usually already contains 60–200 mg of vitamin C, which is worth keeping in mind when adding a separate supplement.

Undesirable combinations

Some combinations require caution or a doctor's consultation. They concern mainly medications and medical conditions, not ordinary dietary supplements.

• Aluminum-containing antacids.Vitamin C enhances the absorption of aluminum; this is especially undesirable in kidney disease.
• Iron chelators (deferoxamine).The combination is possible only under a doctor's regimen, because at the start of therapy vitamin C can increase the toxicity of iron.
• Statins with niacin.In the HATS study, an antioxidant cocktail containing vitamin C weakened the beneficial effect on HDL (Brown et al., 2001).
• Chemotherapy and radiotherapy.The use of antioxidants is coordinated with the oncologist.

Let us separately mention the widespread fear that vitamin C "destroys" vitamin B12. It comes from laboratory experiments of the 1970s and has not been confirmed in clinical practice. Vitamins C and B12 can be taken together.

People with hemochromatosis should avoid not only vitamin C supplements but also combining them with iron-rich food. Here the logic is the opposite of that which applies to athletes with iron deficiency.

Finally, it is worth remembering the cumulative dose: if you take a multivitamin, an "immune" complex, a collagen drink and a separate vitamin C tablet, your total intake may exceed 1–2 g per day without your knowing it.

Editorial conclusions

The best-substantiated combinations of vitamin C are with non-heme iron from plant foods and with collagen or gelatin to support connective tissue synthesis. In dietary doses, its interaction with vitamin E is also beneficial.

High doses of vitamins C and E together during training blocks can blunt adaptation, so they are better left for competitive periods or avoided.

Vitamin C is compatible with most sports supplements, but caution is needed with some medications. Take into account the total dose from all products.

We also recommend the articles "How to take vitamin C: dosage, timing, duration", "Who should not take vitamin C" and "Vitamin B12: what it is and how it works".

References

1. Hallberg L, Brune M, Rossander L. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103–108.
2. Li N, Zhao G, Wu W, et al. The efficacy and safety of vitamin C for iron supplementation in adult patients with iron deficiency anemia: a randomized clinical trial. JAMA Netw Open. 2020;3(11):e2023644.
3. Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K. Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis. Am J Clin Nutr. 2017;105(1):136–143.
4. Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys. 1993;300(2):535–543.
5. Ristow M, Zarse K, Oberbach A, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009;106(21):8665–8670.
6. Paulsen G, Cumming KT, Holden G, et al. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol. 2014;592(8):1887–1901.
7. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345(22):1583–1592.