Dietary Vitamin C and Age-Induced Lipid and Hormonal Metabolic Changes in a Humanized Mouse Model Not Synthesizing Vitamin C and Producing Lipoprotein(a) [Gulo (−/−); Lp(a)+]

Shi L, Rath M, Niedzwiecki A

Journal of Nutrition and Metabolism, vol. 2021, Article ID 5591697, 8 pages, 2021.



The lack of ability to produce vitamin C innately and the ability to synthesize human lipoprotein(a) (Lp(a)) are two unique metabolic features present in humans, compared with most other animal species. The Gulo (-/-) and Lp(a)+ mouse model displays these two features and is therefore suitable for the study of metabolic aspects relevant to human metabolism. It is a well-known fact that vitamin C is essential in collagen synthesis, and in maintaining extracellular matrix integrity, as well as being a powerful antioxidant and cofactor in many metabolic pathways, which makes it a critically important micronutrient for health and healthy aging.

In this study, we investigated the effects of a long-term intake of high and low doses of vitamin C on age-related metabolic lipid and hormonal changes in young (eight to nine months), mid-aged (one year), and old (two years) Gulo (−/−) and Lp(a)+ mice. We observed that chronic vitamin C deficiency resulted in a less healthy metabolic lipid profile, impaired serum insulin-like growth factor (IGF-1), and sex-hormones secretion, all of which can accelerate the development of various pathological conditions in the aging process. The most susceptible to the negative impact of vitamin C deficiency were the young (eight to nine months) and old (two years) mice. Our study conducted in this humanized mouse model indicates that sustained adequate vitamin C intake is essential in maintaining a healthier metabolic profile, important in preventing age-related pathologies throughout the aging process.


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