NMU 266 – Regulating Your Body’s mTOR Signaling Pathway in Cancer Prevention

Nutrition/Natural Medicine Update No 266 (November 22, 2022)

with Dr. James Meschino

Topic: Regulating Your Body’s mTOR Signaling Pathway in Cancer Prevention

Source: J Anti-Cancer Agents Med Chem (2013) and Int J Mol Sci (2019)

You probably have never heard of the mTOR signaling pathway, but in many types of cancer, this signaling pathway is shown to be overactive, causing cancer to develop in the first place and/or promoting its relentless progression.  In this overactive state, the mTOR pathway stimulates cancer cells to divide and helps them form new blood vessels so that tumors can keep growing and spreading to distal parts of the body creating metastatic cancer. Most cancer researchers agree that regulating the mTOR signaling pathway in our body cells from day to day is one more important way we can help to reduce cancer risk and decrease the risk of cancer relapse. It can also slow the rate at which we age. But to be clear, a short-term spike in mTOR signaling is a good thing, as means to preserve or gain muscle mass and bone density, which helps prevent us from becoming weak, frail, and osteoporotic as we age. Consuming ideal amounts of protein and doing resistance exercise training turns on the mTOR pathway in our muscle and bone cells for a short period of time to help us stay strong, enabling us to remain functional as we age. So, a short-term spike or burst in mTOR activity is not a problem. In fact, it is helpful. However, if the mTOR signaling pathway in our cells is constantly turned-on, then we set the stage for cancer, premature aging, and a variety of other health problems.

Regularly consuming excess calories (overeating), especially if it raises your blood sugar (glucose) level into a prediabetic or diabetic range and/or the ingestion of too much animal protein day after day, and/or the accumulation of excess body fat, all result in the mTOR pathway being constantly switched – on in our cells (constitutively up-regulated). This situation is associated with increased cancer risk for many types of cancer and increased risk of cancer recurrence in cancer survivors. As such, regulating the mTOR signaling pathway in your body is something you should keep on your radar from day to day, as part of your cancer prevention strategy. Balancing the short-term turning-on of your mTOR pathway to gain and preserve muscle and bone mass, while counterbalancing this with general inhibition of the mTOR pathway for most of your 24-hour wake-sleep cycle, is a desirable strategy to help to prevent cancer over your lifetime and extend your years of functional life (health span).

So how do you keep the mTOR signaling pathways in your cells from being overactive?

1. Don’t overconsume animal protein. Plant-based protein foods do not stimulate the mTOR pathway as much as animal proteins, which are higher in branched-chain amino acids (leucine, isoleucine, valine). In most cases, you can get away with consuming some low-fat animal protein foods, like skinless chicken breast, turkey breast, egg whites, fish, whey protein, and non-fat yogurt, but balance it out with plant protein foods as much as possible.
2. Stay at your ideal body weight. Being overweight creates insulin resistance. In turn, your insulin, and insulin-like growth factor-1 receptors (IGF-1) on your cells continuously stimulate the mTOR signaling pathway, thereby increasing risk for many types of cancer. Diabetics are known to have a higher cancer risk than non-diabetics, and this is largely due to overactivity of the mTOR signaling pathway.
3. Intermittent fasting and systemic undereating (caloric restriction) can help to silence the mTOR pathway – but its not easy to do, of course. But even if you can regularly restrict food intake for 14-16 hours during your 24-hour wake-sleep cycle it is shown to silence the mTOR pathway and activate longevity genes (Sirtuin genes). As an example, not eating anything between 8 PM and 10 AM the next morning is one way to apply this strategy.
4. Keep your fasting blood glucose level below 90 mg/dl (5 mmol/L), by watching your carbohydrate intake and your waistline.
5. Exercise regularly, both aerobic exercise and strength training – this also activates longevity genes like Sirtuin genes.
6. Consume plant-based foods that contain natural mTOR pathway inhibitors:

• Apigenin – a flavonoid found in abundance in oranges, apples, cherries, grapes, onions, parsley, broccoli, sweet green pepper, celery, barley, tomatoes, and tea.
• Curcumin – a polyphenol found in the spice turmeric
• Fisetin – a flavonoid found in strawberries, apples, persimmons, and onions
• Idole-3-Carbinol – found in cruciferous vegetables, such as broccoli, brussels sprouts, cabbage, cauliflower, Bok choy, and turnips.
• Isoflavones – a class of flavonoid phenolic compounds found in soybeans, such as genistein and daidzein. Consumption of most soy foods provides a generous amount of soy isoflavones
• Quercetin – a polyphenolic compound found in tea, onions, red grapes, and apples.
• Resveratrol – a polyphenol found in the skin of red grapes
• Caffeine is also an inhibitor of the mTOR pathway and regular coffee drinking is associated with a reduction of various cancers (liver, colon, etc.)
• EGCG (Epigallocatechin gallate) – found in green tea and green tea extract supplements, is also an inhibitor of the mTOR pathway. EGCG is well known as a natural agent possessing various anti-cancer properties.

7. In addition to the regular consumption of foods that contain mTOR pathway inhibitors, many health-conscious people take supplements each day that contain some of these mTOR signaling inhibitors, as an additional prevention measure. For instance, many supplements in the marketplace contain:

• Curcumin – often used to reduce inflammation
• Indole-3-carbinol – often used to enhance detoxification and for other cancer-prevention properties
• Soy Extract (containing isoflavones) – for prostate health and to reduce hot flashes during menopause
• EGCG – to help burn excess body fat

All these compounds provide the secondary benefit of toning down the mTOR pathway and thus, they are all associated with decreased cancer risk in many studies. The bottom line on this topic is that one additional way to help reduce cancer development and cancer recurrence is by not overstimulating the mTOR signaling pathways in your body cells on an ongoing basis. This can be done through the targeted nutrition, lifestyle, and exercise information I have provided in this update, and further supported by use of certain dietary supplements, as I have outlined.

I have included the references for this information in the text below.

References:
1. Huang S. Inhibition of PI3K/Akt/mTOR signaling by natural products. Anticancer Agents Med Chem. 2013; 13 (7): 967-970 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775843/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387042/#:~:text=Aberrant%20mTOR%20signaling%20resulting%20from,to%20tumor%20initiation%20and%20progression.

3. https://www.nature.com/articles/s41523-020-00187-4

4. https://www.oncotarget.com/article/25253/text/

Eat Smart, Live Well, Look Great,

Dr. Meschino