Michael Ristow, Hormesis, and Do We Even Need to Fast if we are Low-Carb?
Caveman Doctor has recently received many emails (whatever an email is) from readers asking about intermittent fasting. From information online, you would think that intermittent fasting is the key to heal all health ailments. Also, fasting for those of us that are low-carb and often in ketosis is poorly understood. While the health benefits of fasting are likely enormous, negatives are present, and they need to be addressed. Just as increasing cell death can clear out defective and potential cancerous cells, increasing apoptosis (cell death) can also harm our normal cells. Caveman Doctor also wonders how much we even need to fast if we are in ketosis often, which all cavemen are…
Decreasing Free Radicals: Another Area of Controversy with Fasting
As the caveman diet and lifestyle continually thrive to decrease inflammation and free radicals, we rarely stop and ask ourselves, “Can this actually be detrimental?”
One thing that should come to mind if you are an intermittent faster or pro-autophagy dieter is that apoptosis occurs through free radicals – those pesky little elements we are continually trying to avoid or fight. In fact, those lysosomes in our cells that break down our old and faulty parts rely on free radicals (reactive oxygen species – ROS) to oxidize the old parts.1 While this oxidation can destroy cells and stop them from cancer, it can also damage cells and cause chronic diseases.
So can we blankly prescribe the avoidance of one for the other? If anything, it once again demonstrates the fine interplay between our cells and the processes that keep them running. If you can figure out the appropriate balance, there may be a Nobel Prize awaiting you.
However, this brings up hormesis; the controversial topic that theorizes that stressing the body can result in increasing lifespan. Michael Ristow’s research has shown that perhaps increasing ROS production in our mitochondria (the powerhouses of our cells) through intense exercise makes us produce more defenses against free radicals and as a result, this “stress” can be very beneficial. If this is the case, antioxidants would actually be detrimental. Confused yet?
In fact, Ristow’s group was studying glucose sensitivity during exercise and showed that insulin sensitivity increased only when free radicals were produced. When he gave the study participants antioxidants during exercise to minimize the free radical response, the benefit was lost.2 He is basically showing us that like exercise, ketosis, and fasting, a little stress to our mitochondria actually increase their function. He even goes as far as showing that low-dose lithium can increase longevity in humans!3
Interestingly, lithium increases BCL2, which blocks apoptosis (cell death) and is decreased during fasting.
I am not quite ready for that step, but am happy with “stressing” my body with intermittent fasting, ketosis, and intense workouts. However, Ristow also showed that, much to the chagrin of the calorie restriction and chronic fasting groups, glucose restriction alone may be the key to extending lifespan.4 These results make me question whether fasting is even necessary if we are very low-carb and especially if we are often in ketosis. This is especially important for those of you that don’t tolerate fasting, or just really don’t like to do it…
So we don’t know which amount of stress through exercise, fasting, and ketosis is the right amount. It’s likely that acute stress that is large enough to cause a physical response, but small enough to avoid permanent or severe damage is the best option (as discussed here and here. However, just as the post on autophagy showed the vast benefits of putting our body into recycling mode, there are also some negatives that we should be aware of before entering the world of fasting.
The Major Potential Negatives of Intermittent Fasting:
The Immune System:
Autophagy can decrease the immune system, and while it increases our ability to fight some infections, it may leave us susceptible to others. In fact, some microbes can actually use autophagy for replication.
Autophagy may help cancer cells survive in low-nutrient conditions and in the face of cancer treatment, like chemotherapy. Also, while autophagy does a fine job of cleaning out mutated cells and other products that could lead to cancer; this may not be the case once actual cancer occurs. Cancer cells have many unique methods to stay alive, and they also engage in autophagy and may actually require it for tumor growth5, and can also can use a form of autophagy to cannibalize each other to stay alive under stress and during times without nutrients. As a result, these cells can also stay alive. This is not necessarily a reason to avoid autophagy, as more and more data is showing the benefits of fasting during cancer therapy, however, it may merely place more emphasis on the foods one consumes while they are not fasting, i.e. fasts cycled with high glucose/carbohydrate loads and their increase in insulin may allow cancer cells to enter autophagy during the fast and then proliferate during the feast.
The confusion with autophagy when it comes to cancer and cancer treatment was recently summed up quite nicely with the title of an important article6 in Clinical Cancer Research:
“A Matter of Life or Death (or Both): Understanding Autophagy in Cancer”.
In fact, while autophagy may help cancer cells avoid death from chemotherapy or radiation therapy,7 the cellular pathways affected by intermittent fasting in the schematic from the last post (reference) happen to also increase cancer sensitivity to conventional treatment, like radiation therapy. This would lead us to believe fasting, exercise, and autophagy induction could prove to increase the effect of cancer treatment. Confused yet?
Excessive autophagy may damage the liver. Those with liver damage or dysfunction may want to be extra careful and watched closely under their physician’s guidance.
The Skin and Tissue:
Autophagy can result in decreased wound healing. Those who had a recent operation or cancer patients that are post-operative may want to be cautious in this regard.
These are all food for thought, and while the data is increasing by the minute, much of the work on autophagy is still science mixed with theory. I am still a pro-autophagy kind of guy (and more so a ketosis kind of guy), but I think we do need some science behind the pros and cons of our methods. It seems likely that mimicking the innate methods of autophagy that we have been experiencing for millions of years, such as intermittent fasting, minimizing carbohydrates, periodic ketosis, acute stress, and acute intense exercise, are the forms that ride the fine line between too much and too little providing us with optimal health.
1. Kiffin R, Bandyopadhyay U, Cuervo AM: Oxidative stress and autophagy. Antioxidants & redox signaling 8:152-62, 2006
2. Ristow M, Zarse K, Oberbach A, et al: Antioxidants prevent health-promoting effects of physical exercise in humans. Proceedings of the National Academy of Sciences of the United States of America 106:8665-70, 2009
3. Zarse K, Terao T, Tian J, et al: Low-dose lithium uptake promotes longevity in humans and metazoans. European journal of nutrition 50:387-9, 2011
4. Schulz TJ, Zarse K, Voigt A, et al: Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell metabolism 6:280-93, 2007
5. Kon M, Kiffin R, Koga H, et al: Chaperone-Mediated Autophagy Is Required for Tumor Growth. Science translational medicine 3:109ra117, 2011
6. Hait WN, Jin S, Yang J-M: A Matter of Life or Death (or Both): Understanding Autophagy in Cancer. Clinical Cancer Research 12:1961-1965, 2006
7. Dalby KN, Tekedereli I, Lopez-Berestein G, et al: Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy 6:322-9, 2010
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