Fasting and Polycystic Diseases

posted in: Cancer, Health and Nutrition | 20
Cancer cells growing

Much new and interesting data support the benefits of fasting in diseases other than obesity and type 2 diabetes. This often relates to the role of nutrient sensors in the body. Everybody always believes that increased growth is good. But the simple truth is that excessive growth in adults is almost always bad. Excessive growth is the hallmark of cancer, for example. Excessive growth leads to increased scarring and fibrosis. Excessive growth of cysts leads to the disease of polycystic kidney disease (PCKD) and polycystic ovarian syndrome (PCOS). Excessive growth in adults tends to be horizontal, not vertical. In most cases of adult disease, we want less growth, not more.

This leads naturally to the topic of mechanisms where the body regulates growth. One of the most exciting areas of research focus around nutrient sensors. Insulin is one example of a nutrient sensor. You eat protein or carbohydrates, and insulin goes up. This signals the body that there are enough nutrients to increase growth. Insulin is well known as a growth factor as well and shares a lot of homology with IGF-1 – Insulin Like Growth Factor.

Insulin has long been linked to cancer. Patients with insulin resistance and obesity, conditions characterized by high insulin levels are at high risk of all sorts of common cancers such as lung and colorectal. Diabetics who take insulin compared to those on oral medications almost double their risk of cancer. We will cover these topics in more detail sometime in the future.

But there are other nutrient sensors as well. mTOR is mammalian (or mechanistic) Target of Rapamycin. It was discovered when researchers were looking for the mechanism of action of a novel immune suppressing drug called rapamycin. It enjoys widespread usage in transplantation medicine. Because most anti-rejection medications suppress the immune system, there is an increased risk of cancer. What was unusual about this particular drug was that it decreased, rather than increased risk of cancer. It turns out that mTOR is also a nutrient sensor.

mTOR is mostly sensitive to proteins and certain amino acids. When you eat no protein, mTOR activity is decreased. With rapamycin, you could block mTOR with a drug and this would decrease cellular growth and thus impair certain types of cancer.

A third type of nutrient sensor are the family of proteins known as the sirtuins. Sirtuins were first isolated in 1999 in yeast and SIR stood for Silent Information Regulator. SIRs were subsequently isolated in everything from bacteria to humans and, like mTOR are a group of proteins conserved largely throughout all lifeforms. Interestingly, these proteins directly link cellular metabolic signaling to protein manufacturing.

SIR was first known to be involved in aging when genetic screens of long lived yeast found mutations in the SIR2 gene. Deletion of this gene shortened lifespan where overexpression increased it. In mammals, there are 7 sirtuins SIRT1 to SIRT7 and the most studied is SIRT1. When insulin is blocked, SIRT1 is shuttled out of the nucleus of cells into the cytoplasm, increasing levels (lower insulin = higher SIR1 = good). There is increasing evidence that SIRT1 is profoundly involved in cancer, apoptosis, and neurodegenerative diseases. The effects of SIRT1 on cancer are controversial. The pro-survival effects of SIRT1 may promote cancers, but on the other hand, it also clearly functions as a tumor suppressor. SIRT1 helps with DNA damage repair and thus may reduce cancer rates.

Other than cancer, there are diseases characterized by uncontrolled growth, too. So, in certain diseases, like polycystic kidney disease (PCKD) there is uncontrolled growth of fluid filled cysts in the kidney. This is a hereditary condition which is relatively common. It affects 1 in 1000 people in the general population and constitutes up to 4% of the dialysis population. The genes involved are defects of PKD1 and PKD2 which code for proteins in the polysystin protein complex, but the functions of these proteins are still unknown. These patients develop thousands of cysts in the kidney and liver, which eventually destroys the functional tissue. When the kidneys are destroyed, the patients go into renal failure and require dialysis. Since patients have this from birth, it often takes 50-60 years of this disease to destroy kidney function. Interestingly, it is hypothesized that PCKD cells may also develop metabolic adaptations compatible with an increase in glycolytic activity similar to cancer cells.

The mTOR kinase is thought to play a key role in progression of the growth of these cysts. In mice, supplementation of the diet with branched chain amino acids, specifically leucine (which activate mTOR) significantly increased cyst formation. The authors suggested that “BCAA accelerated disease progression by mTOR and MAPK/ERK pathways. Hence, BCAA may be harmful to patients with ADPKD”.

Everolimus, a drug that blocks mTOR was shown in animal models to be able to delay the growth of these cysts. This drug was tested in PCKD patients in a randomized study published in 2010 in the New England Journal of Medicine. While the drug was able to slow the growth of cysts, it was unable to slow the progression of kidney failure, and mTOR inhibitors are generally not used in the treatment of this disease. These drugs are largely considered a failure in the treatment of PCKD.

However, it does illustrate a very important point. In diseases of uncontrolled growth, the blockage of one of the nutrient sensors is able to slow down this unwanted growth. But what is generally unrecognized is that it simply makes no sense to shut down only one of at least 3 different nutrient sensors. Blocking mTOR pharmacologically does nothing to bring down insulin or increase SIRT1. It turns out that Sirtuins play a role in kidney health, although the effects are still largely investigational.

This therefore brings up an interesting possibility. Rather than trying to block nutrient sensors, why not simply restrict all nutrients, thereby naturally lowering the stimulus to the sensors. This would simultaneously lower insulin and mTOR while raising SIRT1. Wouldn’t it be far more effective to work on all the nutrient sensors to decrease growth, rather than one at a time? What about using therapeutic fasting for the treatment of PCKD? This should be a far more powerful strategy for reducing unwanted growth.

Animal studies show that this could be done successfully. In mice, they use severe caloric restriction reducing intake by 30-50%. Sure enough, the kidney cyst growth was inhibited. While the applicability to humans is unknown and precise molecular mechanisms are unknown, it nevertheless suggests a tantalizing therapeutic strategy for PCKD, but also more broadly to all disease of excessive growth (cancer). Why not simply fast, signalling to the nutrient sensors that no food is available? This will then signal the body to slow down unneeded growth (cyst cells and cancer cells). This treatment is free and available to everybody.

The same exciting possibility exists for PCOS. It is well known that PCOS is intimately connected to insulin resistance. As I’ve argued many times, hyperinsulinemia and insulin resistance are just one and the same disease. High insulin levels will encourage growth of cells. These are diseases of excessive growth, in which insulin, as a nutrient sensor is making it worse. In females of reproductive age, the most rapidly growing cells are the ovaries, so the hormonal environment is encouraging excessive growth of these cysts in the ovaries. With fasting, or any other weight loss, like LCHF diets, for example, decreasing the insulin helps weight loss, but also reverses the PCOS in many cases.

Hyperinsulinemia appears to increase the effect of luteinizing hormone (LH) to increase androgen production (testosterone) which produces many of the clinical effects of PCOS. In addition, insulin decreases Sex Hormone Binding Globulin (SHBG) which increases the amount of free testosterone in the blood which increases the masculinizing symptoms (hair growth etc.) seen in PCOS. While this is an interesting hypothesis, little data exist to show whether this approach will work. However, given the low risk of skipping a few meals here and there, it seems reasonable to give this a try.

20 Responses

  1. Why not simply fast? In simplicity, I see elegance. Thank you Dr. Fung!

  2. Hello Jason,

    could you please explain correlation between HGF and the other growth factors? Because HGF is good for us, isnt it?
    And it increases when we are fasting.

    Thanks for clearing up this for us,

    Eduard

  3. Hello Dr Fung,
    I have a question about Apple cider vinegar/ Bitter melon.. foods that supposedly lower blood sugar. Do these work in a way similar to Insulin? Do they too shove the extra sugar in the already stuffed liver and muscle cells?

    • Hi Jyoti – from what I have gathered from my research – Apple Cider Vinegar i think keeps the liver busy with acetic acid, similar to alcohol (liver wants to work on that first, instead of dealing with glucose), so that it doesn’t create new sugar (gluconeogenesis). I use it help keep overnight liver dumps at bay and it has been working well along with Tulsi tea (that helps keep cortisol levels down, so that it does not stimulate new glucose production in the liver).

      Bitter melon allegedly is an insulin mimetic – both sensitizing receptors and acting as insulin. I have found that after eating something with carbs it can work to keep the spike lower, but I also found – for me at least that it seems to keep my blood sugar higher longer (maybe due to insulin resistance?). I am currently looking at adding gymnema sylvestre (gurmar) and fenugreek (methi seed). Both can block dietary glucose uptake in the digestive system, and fenugreek seems to stimulate beta cell function.

      i would highly recommend Tulsi as a general tonic though. ACV if you have difficulty with Morning Fasting numbers. I know in one blog entry Dr. Fung said not to worry about DP that it is just the liver dumping stored glucose, but if you are in my position, where there isn’t that you have stored glucose to dump and your liver is being extra-helpful by making new glucose instead – it helps with not starting the day much too high, every day.

      • sten bjorsell

        Interesting – vinegar instead of metformin going to bed. Must ask my diabetic-2 friend who now has an automatic glucose monitor installed to check!
        Otherwise, if you are sure that your liver is not dumping glucose when your insulin drops at night (how to be sure??), reduce the protein intake to 0.8 g pure protein per kg target body weight. That would leave “nothing” left to produce glucose of. Gynnostemma drives excess glucose out via the bladder and can cause infection there if used long term, I understand. Tulsi tea also sounds interesting. Is it calming too?

      • Tina,
        Thanks for the reply. Do you take ACV before bed or first thing in the morning?
        I will definitely look for tulsi tea, sounds like a delicious option. I had started using bitter-melon a while back. I juiced about 5 or 6 on a weekend and pour in an ice tray, so I could use one ice cube dissolved in water everyday. Didn’t last long – tastes horrible and I think it made me tired during the day. Might have been my imagination 🙂

        • Jyoti – I take it last thing before bed – 1tbsp in 8oz water. The research says 2tbsps, but I am satisfied with just the 1 and it is less harsh – invariably my morning number is lower than my before bed number. Not MASSIVELY lower, but – considering I was 40-50 points higher every morning before Tulsi (dropped that increase to 10 points lower only) the vinegar will then drop it to within 10pts lower.

          Sten – Tulsi modulates Cortisol levels and has been pretty good for that

          Looking at my logs – and it is important to note diet has not changed – exercise has not changed:

          Where I started – no supplements (7/11/2017):
          PM Before bed (BB): 134
          AM FBG: 171
          This had been going on for a year and half prior – if i went to bed at 150 – it would be 190 on waking – if 140s then 180s.

          With ACV Alone – the next day (7/12/2017)
          PM BB: 156
          AM FBG: 157

          With Tulsi (7/26/2017 – used for one week at that point):
          PM BB: 129
          AM BG: 139

          With Tulsi and ACV (8/1/2017):
          PM BB: 126
          AM BG: 126

          While i drink Tulsi every night – I don’t take ACV every night (usually because I forget).

          I have been taking Tulsi with ALA in the evenings this week, as I want to address some Neuropathy issues i have been having. It hasn’t impacted Fasting numbers any (PM BB 135, AM FBG 141 today), but I have found it seems to be pushing my numbers lower during the day – the other time I test regularly is before Dinner – those early evening numbers have been around 110 all week (normally 130) no changes in diet.

          I like the ALA because it helps me sleep really deeply and I wake up with no foot pain in the morning. Also more energetic. Sometimes with ACV – while it’s powerful for keep fasting numbers flat – it seems to give me crazy dreams and i wake up around 1am to go to the bathroom, and I run hot. Also the foot pain is there when i wake up. I will use it at times, but for now a 10 point overnight increase is acceptable.

  4. There a movement to treat cancer by starvation. It started in 1924 with Otto Warburg (Nobel Laurette, nominated 47 times) who discovered that cancer cells are glucose hungry because a defective metabolic system which uses glucose in the inefficient anaerobic metabolism (about 1/15th the product of ATP compared to aerobic metabolism). Cancer cells can’t metabolize fat, and they are very glucose hungry. Starving cancer by fasting and ketogenic diet works for some, there are a large number of case histories only pharma and our government aren’t interested in finding out what percentage for each type of cancer. Destroying the immune system first with chemo that blocks cells reproduction would negatively impact the starvation since the immune system fights cancer. They have through clinical-trial approval locked starvation trials—see Thomas Seyfried, on YouTube at https://www.youtube.com/watch?v=dm_ob5u9FdM, his recent journal article, or his book Cancer as a Metabolic disease. There are others research trying to spread the message. There current after all these years extensive research in finding a drug to block glutamate—a minor alternate source of energy—“pharma frames the discussion” as Prof. Ben Goldacre writes. However, given glutamate’s wide uses this probably will have terrible side effects. My library of documentaries and lectures on YouTube, each with a deception, is at http://healthfully.org/rh/id7.html
    I could go on and on about autophagy and the health benefits of fasting. Dr. Fung does a great job.

    • Thank you, Jerome, for sharing your knowledge and your YouTube library. I wish Dr. Fung saw a few more younger patients and had more interest in nutritional supplements. He’s wonderful anyway, of course.

  5. As you have pointed out earlier, fasting saves time and money. My breakfast now is just a cup of tea. I only eat lunch if I’m hungry, such as after a gym workout, and dinner is something to enjoy most evenings. Always real food freshly prepared. Mostly low carb, but giving in to tempting treats to avoid cravings without falling into bad habits.

  6. sten bjorsell

    Interesting clever way to take the road of nutrition that affects all growth hormones, while the pharma companies are falling behind from start, focussing on inhibiting one factor at a time.
    But big pharma has the “exposure power”, meaning every new drug can be brought to most of us as in the past, a new “wonder drug”. And I guess they do not want to “harm” the way the majority eat. Big pharma and big food may often be owned by the same people. Another excellent article!
    Yet the difference between good HGH from fasting and the other “bad ones” needs clarification as Eduard pointed out above!

  7. I forgot to mention that I have an extensive library of journal articles on starving cancer, gene swapping with macrophage, glutamate (glutamine) as fuel source, mega vitamin C (Linus Pauling), at http://healthfully.org/rcdm/ . Yes Pharma frames the discussion to promote drug sales.

  8. I spent most of two years trying to get my husband to eat. Anything. His initial weight loss was the clue that his doctor finally had him tested for cancer. I don’t think fasting would be useful in this situation

  9. So would you say that if a patient with pcos who is morbidly obese, not diabetic and more prone to hypoglycemia is NOT getting good results on keto/lchf, they may actually get somewhere if they begin a fasting regimen?

  10. Sarah, As Dr. Fung Writes, it is more important when you eat then what you. The ketogenic diet is too easy to break. It should be also low insulin (low protein). Just skipping breakfast in a study used by Fung, they ate 539 calories less a day, which is consistent with my experience. Just lower your carbs about 50% (especially sweets), replacing them with coconut oil and butter and skipping breakfast should get much better results.
    As stated above check out my video page at http://healthfully.org/rg/id4.html should reinforce what I have written.

  11. As someone who has PKD, I have been anticipating a post discussing this, especially from a nephrologist. I have high hopes that fasting will be able to slow the process of further cyst formation, especially as I already have hundreds throughout my kidneys, liver and pancreas. It isn’t painful, until one of them bursts and the pain is kidney stone-esque. Any available research on PKD suggests it is a form of suppressed autophagy, so perhaps fasting can push back the number of years until I will eventually require dialysis and/or a transplant.
    As I approach 40, I’ve come to terms with having PKD as I’ve seen my father and his siblings struggle with it as they have aged. However, I had my daughter checked a few years back since she was likely to inherit the disease. Although she does have it, it is somewhat comforting that autophagy has come into the limelight these past few years and hope that in her lifetime, more about this process is understood so she avoids some of the complications experienced by her family before her.
    Thank you, Dr. Fung for all that you do in educating others in areas where many of us are ignorant.

  12. Tom Pomeroy

    I would love to have you read this and post on youtube. This is great information, but I listen as I do work or walk. I often don’t have time to sit down and read.

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