Both studies observed significant lung tumor number and size increases in high-Pi diets. Jin et al. reported that a high-Pi diet (1.0%) markedly increased the occurrence of lung tumors compared to a regular diet (0.5%), with notably larger tumor lesions. Lee et al. observed that tumor progression accelerated within the first two months on a high-Pi diet but slowed after prolonged exposure (four months) due to metabolic adaptations. This suggests Pi initially promotes tumor growth but may lead to a state of tumor quiescence over time.
Both studies demonstrated that high Pi intake amplifies the Akt/mTOR signaling pathway. This pathway is essential for cell growth and survival, and its activation was found to support tumor progression. Enhanced phosphorylation of Akt and subsequent increases in protein translation machinery, such as mTOR and 4E-BP1, were reported as essential for synthesizing proteins necessary for cancer cell growth. Lee et al. added that protein translation was notably stimulated during the early stages of tumor development but was downregulated after prolonged Pi exposure, potentially reflecting an adaptive metabolic response in tumor cells.
High Pi intake spurred cellular proliferation and angiogenesis, which are essential for tumor growth and nutrient supply. Increased expression of cell cycle regulators (e.g., cyclin D3, CDK2) and the angiogenic factor FGF-2 was reported in early-stage tumors, correlating with enhanced tumor growth. However, Lee et al. noted a decrease in these factors at later stages, suggesting a switch to a more stable, less proliferative state.
A significant finding in Lee et al.'s study is the role of autophagy in prolonged Pi exposure. Autophagy, the process of cellular recycling under stress, was upregulated in tumor cells subjected to a high-Pi diet over four months. Markers such as LC3 and ATG5 showed increased expression, indicating that the cells might enter a state of quiescence and survival under nutrient-limited conditions, possibly contributing to long-term resistance to tumor growth.
In both studies, High Pi intake was shown to reduce apoptosis, the programmed cell death crucial for eliminating damaged cells. Reduced mitochondrial pro-apoptotic proteins like Bax and caspase-3 activity were observed, suggesting that high Pi enables cancer cells to evade cell death, thereby supporting persistent tumor growth and possibly contributing to more aggressive cancer behavior.
Lee et al. identified significant changes in lung and liver ion levels, with elevated phosphorus, iron, and calcium concentrations reflecting altered metabolic states in these tissues. An upregulation in the tricarboxylic acid (TCA) cycle components was noted, enhancing ATP production. This metabolic shift likely supports the high energy demand of growing tumors, although it later leads to adaptive changes that reduce tumor progression.
The findings from both studies suggest that high dietary Pi can be a risk factor for lung cancer progression. Given its prevalence in processed foods, these results highlight the importance of monitoring dietary Pi intake, especially in individuals at high risk of cancer. Regulating Pi levels in the diet could potentially slow cancer progression, especially in early-stage lung cancer patients, by limiting the nutrient and signaling support tumors require for rapid growth.
The combined research underscores that a high Pi diet initiates rapid early-stage tumor growth through enhanced signaling and cellular proliferation. Over time, metabolic adaptations, including autophagy and quiescence, emerge, possibly leading to more resilient tumors. These insights suggest the need for further exploration of Pi as a modifiable dietary factor in cancer management and prevention.
So be sure to read labels carefully: check the ingredients list to avoid terms like “sodium phosphate,” “potassium phosphate,” “disodium phosphate,” or any other phosphate compounds.
References
Jin H, Xu CX, Lim HT, Park SJ, Shin JY, Chung YS, Park SC, Chang SH, Youn HJ, Lee KH, Lee YS, Ha YC, Chae CH, Beck GR Jr, Cho MH. High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling. Am J Respir Crit Care Med. 2009 Jan 1;179(1):59-68. doi: 10.1164/rccm.200802-306OC. Epub 2008 Oct 10. PMID: 18849498; PMCID: PMC2615662.
Lee, Somin & hu, Kim & Hong, Seong-Ho & Lee, Ah Young & Park, Eun-Jung & Seo, Hwi Won & Chae, Chanhee & Doble, Philip & Bishop, David & Cho, Myung-Haing. (2015). High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer. PloS one. 10. e0135582. 10.1371/journal.pone.0135582.
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