As functional medicine providers, we go beyond traditional medicine and root out underlying causes of health issues as well as attempt to restore normal physiological function and homeostasis. Often during this quest, we recommend nutraceuticals to support recovery. While the physiological effects of nutraceuticals are well-documented, the effects of nutrition at the genetic level are often overlooked. This knowledge can be incredibly useful when managing a variety of patient cases.

Here are three examples of nutrients that have pleiotropic effects on the body:

Vitamin D

Vitamin D might very well be the hero of all pleiotropic nutrients. We think of it as a bone-building nutrient, but its activities span most of our systems. Most cells in our body have vitamin D receptors, and approximately 3% of our genes are regulated by vitamin D. A good example of its pleiotropic effect is seen in immune response modulation. Vitamin D genetically affects the differentiation of CD4+ T cells while enhancing the inhibitory effects of T-cells. Macrophage maturation is also promoted by vitamin D. These pleiotropic effects are not limited to immunity. Vitamin D genetic activity is seen in inflammation regulation, antiapoptotic activity, tumor genesis, severity of type 1 diabetes, regulating the hypertrophy of myocardial cells, and regulating angiogenesis.

Vitamin A

The excretion of sIgA produced by the mucosal cells in the respiratory tract is regulated by the pleiotropic effects of vitamin A. Vitamin A plays an integral role in mucosal homeostasis. The pleiotropic effects of vitamin A on mucosal health include the education of mucosal dendritic cells, enhancing the activity of lymphoid tissue, and improved homing activity within the adaptive immune system.


Minerals such as zinc play important roles in genetic pleiotropy. Zinc and other trace elements regulate pro-inflammatory and anti-inflammatory cytokines. This important interaction becomes more apparent with aging, for which it has been termed “inflammaging.” T-cell and B-cell differentiation and maturation is also partially regulated by zinc.

The Bottom Line

We know that vitamins and minerals play a role in metabolism, energy production, detoxification, enzyme function, hemoglobin production and function, and many other direct physiological processes. We must also remember the effects on genetic expression that foundational nutrients exhibit and how they play an important role in many systems. Considering the prevalence of the nutrient-poor Standard American Diet, it goes without saying that foundational nutrients should be an important tool in every functional medicine provider’s toolkit.

For an in-depth discussion on this topic, check out one of our clinical reference textbooks, Supplementing Dietary Nutrients.


1. Christakos S, Dhawan P, Verstuyf A, Verlinden L, and Carmeliet G. VITAMIN D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiology Review 2016 96:365-408. doi:10.1152/physrev00014.2015. PMID: 26681795

2. Lai YH and Fang TC. The Pleiotropic Effect of Vitamin D International Scholarly Research Notices, Nephrology 2013: Article ID: 898125.

3. Sirisinha S. The pleiotropic role vitamin A in regulation mucosal immunity. Asian Pacific Journal of Allergy Immunology 2015 June; 33(2) 71-89. PMID: 26141028.

4. Mocchegiani E and Malavolta M. Zinc–gene interaction related to inflammatory/immune response in ageing. Genes and Nutrition 2008 July 3(2) 61-75. doi 10.1007/s12263-008-0085-2. PMID: 18850188.

Bill Hogarth, DC, MBS

Bill Hogarth, DC, MBS is a licensed chiropractor in the states of Illinois and Missouri. He holds a doctorate in chiropractic from Logan University and a masters in biological sciences from the University of Minnesota. He has been a functional medicine practitioner and educator for more than three decades.