1) Increases Metabolism (비만)

Retinoic acid is important for 

energy metabolism because it promotes 

energy usage, especially in fat cells [7]. 

It helps activate the gene expression of cells involved in carbohydrate and fat metabolism [7].

RARs can increase lipolysis (the breakdown of fats) and help keep fat levels at a balance. 

Retinoic acid treatment in obese animals induces RAR production, which can lead to weight loss [8].

2) Improves Insulin Sensitivity(당뇨)

Retinoic acid and RAR (RAR) activity also 

improved insulin sensitivity 

and glucose tolerance in animal studies [8].

The improvements in glucose tolerance 

are likely explained by the retinoic acid receptor’s interactions with the cells that produce insulin, pancreatic β cells. 

These cells need RAR activity 

to produce healthy levels of insulin. 

Without RAR activity, the animals had a lower blood insulin level and impaired glucose-stimulated insulin secretion [7, 9]. 

Without RARs, the balance of glucose 

is disturbed [9].

3) Protects the Heart in Diabetics(심장보호)

Diabetes can be a risk factor for heart disease. High blood sugar can induce programmed cell death (apoptosis) of heart muscle cells. 

In addition to having anti-diabetic effects, RARs (RARs) and retinoid X receptors (RXRs) can help prevent diabetes-induced heart failure [10].

In rat heart muscle cells, all-trans retinoic acid activation of RARs and RXRs inhibited cell death. Specifically, RAR-α and RXR-α are required for maintaining heart cell survival [10].

4) Increases HDL Cholesterol

The ABC transporter G1 (ABCG1) assists the body in balancing cholesterol levels. The removal of cholesterol helps prevent high cholesterol and maintain a healthy level of HDL (good) cholesterol) [11, 12].

In laboratory studies of human cells, RAR-α activation increases ABCG1 production, 

which led to an increase in HDL cholesterol ejection from macrophages (a type of white blood cell) [11].

5) Can Potentially Help Treat Alzheimer’s Disease

Alzheimer’s disease is characterized by memory loss and inflammation of the nervous system.

In a mouse model of Alzheimer’s disease, administration of retinoic acid and retinoid X receptor activators helped improve memory [13].

Chromosome region 12q13 (which contains RAR-γ) is associated with late-onset Alzheimer’s disease, and retinoic acid can reduce cellular production of genes involved in early-onset Alzheimer’s disease [14].

Because retinoic acid and its receptors are involved in a variety of pathways that affect Alzheimer’s disease, manipulation of these receptors shows promise for a treatment for the disease [14].

A general review of studies on the retinoic acid receptors (RARs) determined that they facilitate learning and memory processes generally [15].

6) Improves Sleep Quality

RAR-β expression increases delta brain wave activity during slow-wave (deep) sleep. 

Delta wave activity stimulates the release of several hormones that assist in cellular growth and maintenance. Vitamin A deficiency and the lack of RAR-β expression reduces delta power and thus reduces deep sleep [16, 17].

In animal studies, the administration of the retinoic acid receptor activator Am80 improved REM sleep. RAR activation can also slow the age-related decline of sleep quality [18].

7) Essential for Male Fertility

Sperm formation requires the form of retinoic acid called all-trans retinoic acid (ATRA) [19].

In animal studies, RAR-α deficiency in males leads to sterility. Disruption of the RAR-α gene can also lead to poor testicular health and can inhibit sperm production [20, 21].

8) Skin Health

RARs and RXRs are abundantly present in abundance in the skin [22]. Vitamin A, which activates the retinoic acid receptors, is important for the development and integrity of skin [23, 24].

Problems with the receptors RXR, RAR-α, and RAR-γ can cause inflammatory skin diseases and poor skin health [25].

Abnormal metabolism of vitamin A can contribute to psoriasis, ichthyosis, and eczema [26, 27, 28].

Synthetic vitamin A forms, such as tretinoin and isotretinoin, have been developed and used for the treatment of acne and skin aging [29, 30, 31].

9) Critical for Growth and Development

Retinoic acid receptors (RARs) are 

important for development, 

and RAR deficiency can cause developmental defects.

Animal studies show that mice without 

the RAR-α, RAR-β, or RAR-γ genes usually die before or during birth because of developmental defects [32].

All three RAR genes function in mouse brains during later development in embryos and newborns. Studies indicate that RARs are vital for motor function, learning, and memory. Retinoic acid is also required for nerve cell formation in the spinal cord [15].

Embryonic eye development requires RAR activity, and RAR-β absence causes impaired vision in animal studies [33].

Additionally, embryonic inner ear development requires RAR-α and RAR-γ. 

Animals without RAR-α expression exhibit hearing deficiency related to middle ear function, supporting the receptor’s importance for hearing [15].

Animals without RAR-γ exhibit growth deficiency. RAR-γ removal is associated with lower gene expression of factors that are vital for joint formation [34].

In animals, decreased expression of RAR-γ leads to birth defects and growth deficiency and can also cause bone and blood vessel defects [35].

Additionally, the suppression of RARs due to vitamin A deficiency and diabetes can also contribute to skeleton underdevelopment in mouse embryos [36].

RAR-γ plays a critical role in the creation of new blood cells (hematopoiesis). Animal studies also show that RARs help to maintain the balance between the regeneration of blood originating cells and their production [37].

RAR-γ also helps maintain stem cell production [38].

RARs are also needed in the growth and development of important organs, such as the heart, lungs, and digestive tracts. Without RARs, tissues and organs do not develop correctly [15].

10) Support the Immune System

Retinoic acid and its receptors (RARs and RXRs) play important roles in the immune system. 

They play a part in immune cells production and the immune response.

Retinoids and the receptors help in the development of lymphoid organs, 

which are part of the immune system 

and help defend the body against pathogens [39].

RAR activation and retinoic acid activity 

control the development and functions of various immune cells [39].

RAR receptor activation is important for the production of T-cells, 

including [40]:

FoxP3 T regulatory cells

CD4+ (including Th1, Th2, and Th17) T cells

CD8+ T cells

Additionally, retinoic acid and RAR activity suppress inflammation [40].

Retinoic acid itself, as well as expression of the receptors RAR-α and RAR-β, promote Th2 dominance and suppress Th1 cytokines [40].

Deficiencies of retinoic acids 

can decrease immune function [40].

11) Can Help Prevent Leaky Gut

Leaky gut, also called intestinal permeability, 

is a condition where the gut lining has an increased permeability. 

This exposes microbes, toxins, and food particles to the immune system where they produce inflammation. 

Leaky gut is associated with several autoimmune diseases, allergies, and other inflammatory health problems [41].

RAR-α helps maintain barrier function 

and helped reduce the breakdown 

of the intestinal barrier in cell-based studies [42].

Retinoic acid acts via the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) to help gut tissues to develop. 

Intercellular tight junctions help keep the intestinal epithelial barrier in place. 

RAR activation is important for tight junctions between cells in the gut to form correctly [42]. 

Therefore, vitamin A supplementation can improve gut barrier integrity [43] 

and Vitamin A deficiency hampers gut barrier function [44]. 

Additionally, retinoic acid depletion leads to the disruption of functional tight junctions, another factor that increases gut permeability [42].

12) May Treat Multiple Sclerosis

In animal studies, all-trans retinoic acid 

(ATRA, an activator of RARs) was able to reduce the severity of experimental autoimmune encephalomyelitis, which is an animal model of multiple sclerosis [45].

In animal studies, ATRA and Am80 (synthetic RAR-α and RAR-β activators) suppressed inflammation in optic nerve fibers. 

The activation of the RARs helped reduce eye inflammation and protected the optic nerve. 

This neuroprotective and anti-inflammatory effects of RAR activators suggest that RAR activation 

may potentially help treat multiple sclerosis in humans [45].

13) Cancer

By changing gene expression, 

RARs can inhibit the growth of many types of tumor cells [46, 47]. 

However, the roles of RARs 

in cancer are mixed. 

RAR expression seems to stimulate cancer growth in some cases while inhibiting it in others.

Lung Cancer

There is conflicting evidence on the retinoic acid receptor’s role in lung cancer.

The loss of RAR-β occurs in lung cancer cell lines. Scientists think that defective retinoid receptor expression might be involved in lung cancer [48].

In studies of human lung cancer cell lines, the activation of RARs and RXRs contribute to the induction of the RAR-β gene. Then, RAR-β expression leads to growth inhibition and apoptosis (programmed cell death) 

of the cancer cells by retinoids [49].

RAR-β2 is associated with fewer lung tumors in animals. 

Scientists thought that RAR-β might function as a tumor suppressor gene [50, 51].

However, in a study of 595 patients with non-small-cell-lung cancer (NSCLC), RAR-β gene expression is associated with a poor prognosis. This result conflicts with previous research that RAR-β can help suppress lung tumors [52].

Two hypotheses might be able to explain these conflicting results. One hypothesis is that, in lung cancer, RAR-β might be inactive and cannot suppress tumors. The other hypothesis is that an increase in RAR-β4 might enhance cancer growth [52].

RAR-β may play a double role and affects both tumor suppression and tumor promotion [53].

Breast Cancer

Around 70% of breast cancer cells have the estrogen receptor-α (ER-α) nuclear receptor. 

RAR-α is an estrogen target gene. 

Estrogen-mediated transcription 

and cell proliferation require RAR-α [54].

RAR-α plays an essential role in activating estrogen-mediated gene expression 

and can help with estrogen treatments of breast cancer. In a study of 263 breast cancer patients with ER-α, the presence of the RAR-α gene was associated with positive clinical outcomes [54].

Although its mechanisms are unclear, RAR-α and ER-α can work together to help treat breast cancer [54].

Additionally, the loss of RAR-β expression occurs early in the formation of breast cancer cells. Even though its mechanism is unknown, RAR-β seems to play a part in breast tumor suppression [55].

Stomach Cancer

In stomach cancer cells, the RAR-α and RAR-β genes have lower levels of expression in stomach cancer tissue as compared to normal tissue [56, 57].

Higher levels of RAR-α expression in stomach cancer cells is associated with a positive prognostic factor for survival. RAR-α expression positively correlates with the responsiveness to all-trans-retinoic acid therapy. This indicates that retinoids may show promise in the treatment of stomach cancer [57].

Oral Cancer

RAR-β expression in oral cancer cells is associated with a better response to cancer treatment. 

While it may be a marker for the prevention of oral cancer, it does not directly influence the cancer cells [58].

However, the overexpression of RAR-α in the cells of oral cancer patients is associated with a poor prognosis [59].

Other Cancers

The loss of RAR-γ expression in skin cells is associated with skin cancer [60].

In cervical cancer cell lines, RAR-β can potentially lower the production of oncogenes (genes that can turn normal cells into cancer cells) [61].

Mutations in the RAR-α gene is associated with leukemia [62].