Regenerative Farming: Can It Address Immunosuppression with Better Nutrition?

Global crop yields are at their highest in recorded history, but simultaneously at record lows nutritionally [1]. Because conventional farming practices prioritize high yields, quality has precipitously declined over the decades [1, 2]. To produce higher yields, farmers are incentivized to use chemical fertilizers and pesticides which can significantly reduce a crop’s nutritional value. Researchers are finding, for example, that chemical fertilizers reduce zinc, copper, and iron density in crops [3, 4, 5]. In addition, pesticide interference with microbial communities in the soil reduces symbiotic interactions between the crops and microbes. This can disrupt the crop’s ability to extract micronutrients such as vitamins, minerals, and amino acids from the soil, which ultimately produces a less nutritional crop [6]. Unfortunately, consuming affected crops means a reduced micronutrient intake for many. According to the National Academies of Sciences, Engineering, and Medicine  (NASEM) (2019), the recommended daily intake of iron, zinc, and copper are 8mg/day, 11mg/day, and 900µg/day respectively for males. For females, it is 18mg/day, 8mg/day, and 900µg/day, respectively. Continued consumption of these ‘empty’ crops could contribute to widespread mineral deficiencies, and fail to meet these benchmarks despite eating calorically appropriate amounts of food.

The implications of declining nutritional intake can pose severe consequences for human health - the immune system is a clear example of this fact [7, 8, 9]. Poor intake of micronutrients such as iron, zinc, and copper can cause impaired immune responses. For example, those affected could lose iron's anti-cancer qualities [10] or zinc's ability to upregulate T-cell response [11]. Supplements for these micronutrients are a solution for those with access, but this does not address the root problem. A more comprehensive proposition made in recent years has been regenerative farming - a collection of sustainable farming practices whose primary focus is revitalizing farm soil while maintaining yield. These practices commonly consist of rotating crops to prevent overreliance on particular nutrients, using microbiome-friendly fertilizers like cow manure, and more [6]. Regenerative farming, unlike supplements, can be an accessible public health tool for developed and developing countries, as it doesn’t require sophisticated or expensive equipment. It is an attractive public health measure, as reducing micronutrient deficiencies simultaneously reduces certain disease susceptibilities [9, 12, 13]. Research suggests regenerative farming can address these mineral deficiencies by improving soil quality and nutrient bioavailability in crops. Techniques such as crop rotation—where different crops are cycled yearly to prevent the depletion of specific soil nutrients—and the use of organic fertilizers to promote microbial growth have been shown to improve crop nutritional content.  For example, Streptomyces, a bacteria in the soil around plant roots known as the rhizosphere, secrete Indole Acetic Acid (IAA), which functions as a plant growth hormone [1, 6]. Other practices include a ‘no-tillage’ approach, as tilling alone can hinder a crop’s ability to extract minerals from the soil [1, 6]. This review will explore the long-term decline in iron, zinc, and copper concentrations for many crops, its implications for the immune system, and how regenerative farming can alleviate these trends.

Section 1: Current conditions of food and soil

Soil nutrient density has been steadily deteriorating over time, largely due to the use of conventional fertilizers and tillage methods [4]. Addressing the claims about the influence of fertilizer, the International Fertilizer Industry Association (IFIA) (2023) found that nitrogen fertilizers account for about 56% of all fertilizers used worldwide. Although Nitrogen fertilizers increase crop yield, they are suspected of stripping crops of zinc and copper, according to Gollany, et. al (2019). Their findings suggest that bioavailable copper levels in wheat decreased as Nitrogen fertilizer usage increased, proportionately. They also observed a 43% and 53% decrease in zinc and copper, respectively, when comparing tilled and fertilized soil to a control pasture. From this, they concluded that Nitrogen fertilizer and conventional tillage significantly decrease mineral levels in wheat. They also noted that conventional tilling methods (using moldboard plows) caused less iron to be absorbed by wheat. 

Another type of fertilizer, accounting for 24% of fertilizer used by farmers, is Phosphorus-based [14]. A study done with Phosphorus fertilizers and wheat had similar findings to Gollany, et. al (2019). Dun-Yi L., et. al (2019) found that Phosphorus fertilizers decreased zinc accumulation in wheat in both acid and calcareous soil. These data indicate that conventional farming practices seem to strip both soil and crops of their micronutrients. Notably, tomatoes, corn, watermelon, bananas, apples, oranges, and potatoes suffer from mineral losses as well. Over the last 50-70 years, all of the aforementioned crops have lost between 24-27% iron, 20-76% copper, and 27-59% zinc levels [2]. Conventional farming, therefore, may contribute to the zinc, copper, and iron deficiencies suffered by more than two billion people on Earth [2]. If these deficiencies persist, fundamental functions of the immune system can fail, or be greatly suppressed.

Section 2: How declining nutrition can reduce the adaptive immune response.

The minerals copper, iron, and zinc are just a few of the many micronutrients necessary for adaptive immunity. Iron, for example, is used to maintain a healthy white blood cell (WBC) count. Iron deficiencies, therefore, inhibit immune cell production and activation [9]. For example, Frost, N., et. al (2022) demonstrated that the generation of mature neutrophils (a type of WBC) was significantly suppressed in iron-deficient mice. Interestingly, pre-clinical trials also suggest that, without iron, T cells fail to properly detect and kill malignant B cells, a hallmark symptom of Leukemia [10]. Zinc, on the other hand, shows its importance via T-cell function. Colomar-Carando N., et. al (2019) observed that naive T-cells without zinc could multiply, but were functionally useless as they could not activate. This means that someone low in zinc would have trouble activating their T-cells when encountering pathogens, and antibody levels would be noticeably reduced. Finally, copper is used for the proliferation and differentiation of T cells [7]. So, while zinc ensures proper cell function, copper ensures proper cell count. Other studies found that, without copper, Neutrophil Extracellular Trap (NET) complexes would not form properly. These complexes are vital due to their role in the inflammatory response, trapping pathogens, and activating other immune cells [10]. 

It is well-reported that micronutrient deficiency-related deaths are often caused by comorbidities, such as respiratory disease (e.g. pneumonia) and diarrhea [8, 12]. Addressing these deficiencies via nutrition fortification and regenerative farming could be a successful alternative to mass supplementation.

Section 3: Regenerative farming and its role in replenishing micronutrients

Regenerative farming is the practice of incorporating diverse rotations, cover crops, organic fertilizers, and a no-tillage approach [1, 5]. These methods have shown promising results in enhancing soil quality and, as a result, food quality. Montgomery D. R., et. al (2022) found that, over 5-10 years, no tilling and cover cropping increased zinc in wheat and cabbage by 56% and 50% respectively. Similarly, an average of 27% more copper was demonstrated in cabbage, sorghum, corn, soy, and peas. They also found that chemical fertilizers and pesticides altered the soil biome, reducing mineral absorption in the plants. These findings are supported by Singh I., et. al (2023), who found that pesticide use disrupted the symbiotic relationships formed between microbial flora and crops. Microbial flora support plants by secreting essential nutrients or protecting plants from certain pathogens [6]. Symbiotic relationships enhance the crops’ uptake of minerals but also address high-yield demands as fewer crops will succumb to disease. However, there isn’t a full consensus on whether the regenerative practices increase the iron, zinc, and copper concentrations for every crop tried. For example, Omondi E., et. al (2022) found that using organic fertilizers has been shown to only increase iron concentrations in crops such as lettuce, carrots, potatoes, and beets, among others. Zinc and copper, however, didn’t have a significant difference under the same conditions. For oats, only zinc was affected by the tillage method. Gollany, et. al (2019) also reported the disparity in the research. They reported claims that extractable iron, zinc, and copper increased under conventional farming, but others reported the opposite. More research should be done to establish the crops that are more responsive to conventional or regenerative farming techniques. 

Conclusion

The purpose of this review was to evaluate the current issues that arise from conventional farming practices, examine how the immune response is altered by a low-micronutrient intake, and highlight how this could be alleviated by regenerative farming. Current research finds that nutrition levels in food are declining, which has serious health implications [1, 7, 8, 9, 10]. This review then explored how three specific micronutrients: iron, zinc, and copper are all affected by these trends, and how this can noticeably reduce people’s immune response [7, 8, 9, 13]. Research suggests that regenerative farming can address these concerns, but more research should be done to see which crops it revitalizes best. In some instances, it increased mineral density for only one of the three minerals in crops of interest [1, 4, 5]. However, there are still promising results that suggest regenerative farming can alleviate mineral deficiencies experienced by almost ⅓ of the world population [6].

About the Author: Adam Price

My name is Adam Price, and I grew up in the suburbs of Houston, Texas. I came to California for university, and to be closer to my Dad who retired in Monterey many years ago. I have a passion for the medical sciences, and hope to start my own practice one day! My interests are endocrinology, basketball, business, and shoes. I have always liked writing as it forced me to learn more about the world, and it is so exciting to finally have a chance to publish one of my prouder works!

Author's Note

The idea to write a review on micronutrients stemmed from a post I saw on social media. It was a video of a professor giving a speech on how soil is becoming less nutritious, and my first instinct was to ask: is this true? Like many things you may see online, I thought it was another post trying to lure me into buying a product. But, I had to be sure. I felt this urge to verify this information out of anxious curiosity. I have always been neurotic about what I put in my body because health is not guaranteed - it can take a turn at any moment. But, with proper nutrition, this chance becomes minimal. In a way, I have the social media post to thank for inspiring this review, as it forced me to disprove it… but it turns out it was right. My review, therefore, discusses how micronutrients in soil and food have been declining, and what this means for our health. As you may conclude, health is quite an umbrella term. So, for the sake of a 1600-word limit, I decided to focus on the immune system. Enjoy!

References

1. Montgomery DR, Biklé A, Archuleta R, Brown P, Jordan J. 2022. Soil health and nutrient density: preliminary comparison of regenerative and conventional farming. PeerJ [Internet]. 10: e12848. DOI: 10.7717/peerj.12848.
2. Bhardwaj RL, Parashar A, Parewa HP, Vyas L. 2024. An alarming decline in the nutritional quality of foods: the biggest challenge for future generations’ health. Foods [Internet]. 13(6): 877. DOI: 10.3390/foods13060877.
3. Chen X, Zhang W, Wang Q, Yu-Min L, Dun-Yi L, Zou C-Q. 2019. Zinc nutrition of wheat in response to application of phosphorus to a calcareous soil and an acid soil. Plant Soil [Internet]. 434(1-2): 139-150. DOI: 10.1007/s11104-018-3781-3.
4. Shiwakoti S, Zheljazkov VD, Gollany HT, et al. 2019. Micronutrients decline under long-term tillage and nitrogen fertilization. Sci Rep [Internet]. 9: 12020. DOI: 10.1038/s41598-019-48408-6.
5. Omondi EC, Wagner M, Mukherjee A, Nichols K. 2021. Long-term organic and conventional farming effects on nutrient density of oats. Renew Agric Food Syst [Internet]. 37(2): 113-127. DOI: 10.1017/S1742170521000387.
6. Singh I, Hussain M, Manjunath G, Chandra N, Ravikanth G. 2023. Regenerative agriculture augments bacterial community structure for a healthier soil and agriculture. Front Agron [Internet]. 5: 1134514. DOI: 10.3389/fagro.2023.1134514.
7. Gombart AF, Pierre A, Maggini S. 2020. A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutrients [Internet]. 12(1): 236. DOI: 10.3390/nu12010236.
8. Yu L, Yousuf S, Yousuf S, Yeh J, Biggins SW, Morishima C, Shyu I, O'Shea-Stone G, Eilers B, Waldum A, Copié V, Burkhead J. 2023. Copper deficiency is an independent risk factor for mortality in patients with advanced liver disease. Hepatology Communications [Internet]. 7(3): e0076. DOI: 10.1097/HC9.0000000000000076.
9. Frost JN, Wideman SK, Preston AE, Teh MR, Ai Z, Wang L, Cross A, White N, Yazicioglu Y, Bonadonna M, Clarke AJ, Armitage AE, Galy B, Udalova IA, Drakesmith H. 2022. Plasma iron controls neutrophil production and function. Sci Adv [Internet]. 8(40): eabq5384. DOI: 10.1126/sciadv.abq5384.
10. Bordini J, Morabito A, Taccetti C, Lenzi C, Ranghetti P, Perotta E, Frenquelli M, Scarfò L, Albi E, Ghia P, Campanella A. 2023. High dose iron impairs malignant B-cell viability and improves immune antitumor functions in chronic lymphocytic leukemia. HemaSphere [Internet]. 7(3): e0182. DOI: 10.1097/HC9.0000000000000182.
11. Colomar-Carando N, Meseguer A, Company-Garrido I, Jutz S, Herrera-Fernández V, Olvera A, Kiefer K, Brander C, Steinberger P, Vicente R. 2019. Zip6 transporter is an essential component of the lymphocyte activation machinery. J Immunol [Internet]. 202(2): 441-450. DOI: 10.4049/jimmunol.1800689.
12. Bauer CD, Mosley DD, Samuelson DR, Poole JA, Smith DR, Knoell DL, Wyatt TA. 2024. Zinc protects against swine barn dust-induced cilia slowing. Biomolecules [Internet]. 14(7): 843. DOI: 10.3390/biom14070843.
13. Zhou X, Wang H, Lian S, Wang J, Wu R. 2021. Effect of copper, zinc, and selenium on the formation of bovine neutrophil extracellular traps. Biol Trace Elem Res [Internet]. 199(1-2): 3312-3318. DOI: 10.1007/s12011-020-02477-1.
14. Statista Research Department. Global fertilizer consumption by nutrient 1965-2022. Accessed August 25, 2024. Available from: https://www.statista.com/statistics/438967/fertilizer-consumption-globally-by-nutrient/.
15. National Academies of Sciences, Engineering, and Medicine. 2019. Dietary Reference Intakes for Sodium and Potassium. Washington (DC): The National Academies Press [Internet]. Available from: https://doi.org/10.17226/25353.