Matthew Messer

Matthew Messer

Editor-in-chief

They are most effective applied in a combined form, as they enhance rather than block each other’s effect. 

Various controversies can be read about vitamins A and D. Some claim that vitamin A inhibits vitamin D’s functions, while others merely ignore their interaction and push vitamin D on its own. 

Numerous studies have been conducted on the two vitamins’ connection. While taken separately they can decrease each other’s levels, with their combined use this problem ceases to exist. What’s more, they protect against each other’s negative effects: if taken with vitamin D3 even a much larger amount of vitamin A won’t lead to an overdose. (1) The reverse is also true: a more than necessary amount of vitamin D3 does not increase the chances of calcification if it is combined with an adequate vitamin A intake (2) A recently published study serves as proof. 

Combined vitamin A and D3 most effective against stroke  

A study published in 2020 examined the use of vitamins A and D3 in stroke prevention.(3) The study was conducted with the participation of four groups: group one received only vitamin A, group two received only vitamin D3, the third group received both, and the fourth group neither. Above all, the researchers were interested to examine how these different therapies affect the risk of stroke, but they also took note of the changes in vitamin A and D levels as a result of the use of supplements.  

All groups received 50.000 IUs of vitamins A and/or D3 once a week. Those given both received vitamins A and D3 together, at the same time, except for the control group, of course, who only took placebos. Participants were examined both at the beginning and end of the three-month experiment to compare their vitamin A and D levels, the level of inflammation in their system, and their risk of stroke.  

Taking vitamin A supplements on their own decreased the level of vitamin D, and in turn, taking vitamin D supplements on their own led to decreased levels of vitamin A. That’s why many don’t recommend vitamin A: if taken with inadequate amounts of vitamin D3 it can increase vitamin D deficiency. But here comes the crucial part of the study: the combined use of vitamin A and D3 increased both vitamin A and D levels more than the same dosage taken in itself. What’s more, vitamin D supplements combined with vitamin A were three times more effective in increasing blood levels as taking a vitamin D supplement on its own. It’s clear that vitamins A and D do absolutely not inhibit each other’s effect, nor does vitamin A decrease the level of vitamin D. On the contrary, their combined use reduced the levels of inflammation by 75%. Compared to the control group who only received traditional stroke treatment, group three’s risk of stroke was reduced by 50% by the end of the experiment. On its own, however, neither vitamin A nor vitamin D decreased inflammation or stroke risk significantly. 

Why is the combined use of vitamins A and D so effective?  

Vitamins A and D are both vital parts of our immune system. They support the production and function of white blood cells in several ways, and they keep excessive immune activity in check through anti-inflammatory and antioxidant functions.(4, 5) Both vitamin A and D deficiencies can be observed in the case of chronic illness. Vitamin A deficiency increases the risk of cardiovascular disease; the lower the level, the higher the risk.(6) (7)  

According to several studies vitamins A and D3 improve each other’s effect in synergy and if one’s level drops, the other will not work as efficiently. (3, 8, 9) Vitamin A is needed to activate vitamin D, and their combined use reduces inflammation much more effectively and protects tissues from oxidative stress. The above-mentioned study unequivocally refutes the mistaken conclusion that supplementing vitamin A has an adverse effect on supplementing vitamin D3 or on vitamin D levels. Their combination increased the levels of both vitamins the most and decreased inflammation and the risk of stroke the most effectively. 

  1. Myhre AM, Carlsen MH, Bøhn SK, Wold HL, Laake P, Blomhoff R. Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. Am J Clin Nutr. 2003 Dec;78(6):1152-9. doi: 10.1093/ajcn/78.6.1152. PMID: 14668278. 

  2. Fu X, Wang XD, Mernitz H, Wallin R, Shea MK, Booth SL. 9-Cis retinoic acid reduces 1alpha,25-dihydroxycholecalciferol-induced renal calcification by altering vitamin K-dependent gamma-carboxylation of matrix gamma-carboxyglutamic acid protein in A/J male mice. J Nutr. 2008 Dec;138(12):2337-41. doi: 10.3945/jn.108.093724. PMID: 19022954. 

  3. Kadri A, Sjahrir H, Juwita Sembiring R, Ichwan M. Combination of vitamin A and D supplementation for ischemic stroke: effects on interleukin-1ß and clinical outcome. Med Glas (Zenica). 2020 Aug 1;17(2):425-432. doi: 10.17392/1137-20. PMID: 32567290. 

  4. Muscogiuri G, Annweiler C, Duval G, Karras S, Tirabassi G, Salvio G, Balercia G, Kimball S, Kotsa K, Mascitelli L, Bhattoa HP, Colao A. Vitamin D and cardiovascular disease: From atherosclerosis to myocardial infarction and stroke. Int J Cardiol. 2017 Mar 1;230:577-584. doi: 10.1016/j.ijcard.2016.12.053. Epub 2016 Dec 26. PMID: 28043680. 

  5. Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of Vitamin A in the Immune System. J Clin Med. 2018 Sep 6;7(9):258. doi: 10.3390/jcm7090258. PMID: 30200565; PMCID: PMC6162863. 

  6. Wang H, Chen W, Li D, Yin X, Zhang X, Olsen N, Zheng SG. Vitamin D and Chronic Diseases. Aging Dis. 2017 May 2;8(3):346-353. doi: 10.14336/AD.2016.1021. PMID: 28580189; PMCID: PMC5440113. 

  7. Min KB, Min JY. Relation of serum vitamin A levels to all-cause and cause-specific mortality among older adults in the NHANES III population. Nutr Metab Cardiovasc Dis. 2014 Nov;24(11):1197-203. doi: 10.1016/j.numecd.2014.06.004. Epub 2014 Jun 27. PMID: 25149896. 

  8. Lin LM, Peng F, Liu YP, Chai DJ, Ning RB, Xu CS, Lin JX. Coadministration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: An in vivo and in vitro study. Atherosclerosis. 2016 Aug;251:273-281. doi: 10.1016/j.atherosclerosis.2016.06.005. Epub 2016 Jun 3. PMID: 27428295. 

  9. Anand PK, Kaul D, Sharma M. Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria. J Microbiol Immunol Infect. 2008 Feb;41(1):17-25. PMID: 18327422. 

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