Two interesting medical case-reports caught my eye last week. I want to tell you about them because they’re different avenues to appreciating the importance of metabolism in health and disease, something I already emphasize when discussing diet.
Reversing brain damage with oxygen therapy
The first case-report is about reversing brain damage in a 2-year old girl in America . However interesting these sort of medical firsts are, we should remember not to overgeneralize these encouraging results because we’re dealing with a sample size of 1. Furthermore, the girl’s doctor is co-owner of Harch Hyperbarics, Inc., a company offering hyperbaric medicine consulting. With these caveats in mind, let’s explore what happened.
She was found face down in a 5°C (41°F) pool where she had been for at least 15 minutes and was resuscitated 1 hour and 40 minutes later. Sadly this left her in a semi-vegetative state, rated as a 3 on the 1 to 6 Glasgow Coma Scale, where nonsense is uttered, eyes respond to voice but there’s abnormal flexion of the limbs upon painful stimuli. She had serious brain damage.
Her doctor Dr. Harch decided to give her pure oxygen to breath through her nose.
She responded positively! Her parents were asked to film her before and after inhaling the oxygen in order to assess her response [video]. For a few weeks she continued to receive 2L of oxygen per minute for 45 minutes twice a day and kept making progress.
Eventually the doctors upgraded her oxygen treatment to hyperbaric oxygen therapy (HBOT). This lasted another few weeks and involved getting into a chamber pressurized to 171.21 kPa, or 1.3 times the pressure of our normal outside atmosphere (1 atmosphere = 131.7 kPa) for 45 minutes once a day.
To give you an idea of how immediate the effects of HBOT were on this little girl, within hours after it she had better gross motor functions, vocabulary, alertness and was much less ‘floppy’ (decreased tone). After 10 session of HBOT, her mother reported her being essentially back to normal except for gross motor functions (walking around, picking something up…) [video1, video2].
After 40 sessions of HBOT, which was 162 days after nearly drowning, she
“demonstrated mild residual injury and near-complete reversal of cortical and white matter atrophy” 
That is the headline grabbing statement. Although doctors know that adult brains are much more malleable in terms of repair and growth than previously assumed, this level of damage reversal, even in a child, is the first of its kind.
How might oxygen therapy have helped?
Dr.Harch thinks the higher oxygen levels signaled certain of her genes to regrow white and grey matter. It’ll have to be checked with gene expression tests in other patients with some sort of brain damage showing signs of recovery.
In addition to Dr.Harch’s opinion, what we already know about how the body uses oxygen can clue us in. Our tissues usually get their oxygen from a molecule called hemoglobin. It straps oxygen onto its back, carries it around in the blood so it can let go of it when our network of arteries, veins and capillaries finally delivers it to the right place (tissue). That’s one way for our tissues to get oxygen.
The other way is through diffusion. Oxygen is not only bound to hemoglobin in our blood but some of it also floats around freely. In the latter case, oxygen can diffuse straight from the bloodstream into tissues without hemoglobin’s help.
This happens because a concentration gradient exists between tissues and the blood. The higher the concentration of oxygen in the blood and the lower the concentration of it in the tissue, the bigger the concentration gradient. Nature is such that the concentration wants to even out, so some oxygen from the blood will diffuse over into the tissue until the blood and tissue have more or less the same oxygen concentration.
For example, in your heart, oxygen will diffuse into the first few layers of the coronary artery (tunica intima) according to the inverse-square law: 1 ÷ distance². Don’t worry about the equation, all it means is that if oxygen in the blood is too distant from the tissue, then it won’t diffuse into it well and is better off using a carrier molecule like hemoglobin.
Of the many cool things HBOT does, one is that it takes advantage of how oxygen can diffuse into tissues. HBOT saturates blood with oxygen, allowing more precious oxygen to diffuse into tissues and thus help them support their energy needs (oxygen is needed to sustain a large portion of energy production.) Keep in mind that the energy budget of tissues is often stretched thin when lots of repair needs to happen and hemoglobin’s delivery of oxygen may not always be enough or optimal.
HBOT has also been used to heal wounds because wound healing requires the growth of new blood vessels (angiogenesis). Angiogenesis contributes to the repair and re-growth of new brain cells – could HBOT have helped repair this little girl’s brain in this way? 
Blast cancer with a metabolic arsenal
The second case-report is about an overweight woman in Turkey reversing her stage 4 triple-negative breast cancer . Unlike the first case-report it isn’t the first of its kind, people have come back from advanced breast cancer. However, the specific therapy and extent of recovery make it a fascinating and encouraging medical news item.
Doctors working with this woman called their approach metabolically supported chemotherapy (MSCT). It involves administering chemotherapy with a multi-pronged metabolic strategy consisting of a ketogenic diet, hyperbaric oxygen therapy (HBOT) and hyperthermia. After seeing essentially total reversal of her condition, she had a mastectomy, a surgery to remove any remain cancer.
The main idea behind MSCT is that we want to take advantage of the fact that cancer cells respond to stressors differently than normal cells. For example, by stressor we mean a metabolic poison messing with your cells’ energy production or a lack of oxygen (hypoxia).
The key to understanding why stressors, seemingly bad things at first, can be useful medical tools is that their effects are highly context and dose dependent. The idea behind chemotherapy is quite simple really: poison the cancerous cells quicker than the healthy cells so that the cancerous ones die before the healthy ones do.
MSCT is ‘simply’ increasing a cancer cell’s susceptibility to stressors and/or increasing a healthy cell’s ability to resist stressors.
This video shows how advanced and widespread this woman’s cancer was. The brightest parts are the cancer and the darker parts normal tissue.
This video shows total remission of this woman’s cancer. Astonishing! You don’t need to be an oncologist to realize how big the difference is between the first and second video.
We’ll explore the multi-pronged metabolic approach ignoring HBOT because we’ve already discussed it above.
What did her ketogenic diet look like?
The first thing to notice is that this is a pretty varied, tasty, sustainable and nutrient dense diet. She wasn’t advised to restrict her calories yet seems to have done so inadvertently, since her BMI dropped from 28 to 21.8. Calorie restriction is well known to enhance the therapeutic effects of ketogenic diets .
Her ‘well formulated’ ketogenic diet is very different from the liquid formula ones used to treat epileptic kids. Don’t get me wrong, these liquid formulation get impressive results but they are not “nutritionally complete” as sometimes claimed .
A growing number of case-reports and small clinical trials point to ketogenic diets as a viable treatment option for many, if not all, cancers. There are multiple ways in which ketogenic diets are thought to help but I’ll only expand on a few here. Which of these mechanisms are in fact in play isn’t quite clear yet.
The major mechanism put forth involves exploiting something called the Warburg Effect. It’s named after the Nobel prize winning biochemist Otto Warburg. He was so brilliant Einstein pleaded in vain that he continue his research rather than go fight in the first world war (for which he was awarded the Iron Cross in 1918) .
Anyways, the Warburg Effect occurs when, a cell which normally gets most of its ATP by using oxygen and fat, gets it instead by fermenting sugars even when oxygen is present. The presence of oxygen is normally enough to get the cell to use oxygen, but not so when the Warburg Effect is present.
Because a ketogenic diet contains little to no glucose, the cells of a person eating this way are forced to make lots of their ATP using fats and ketones. This is normal easy peasy stuff for (nearly all) healthy cells in your body, but not for cancer cells given their sugar fermentation addiction. Their machinery is set up for the latter rather than for fats and ketones. One popular way to describe the demise of cancer cells in this context is that they die of an energy crisis [8,9,10,11].
Chemotherapeutic MCL-1 resistance is downregulated
MCL-1, short for induced myeloid leukemia cell differentiation protein, is overexpressed in chemotherapy resistant cancers. It seems to play a role in resisting the poisonous effects of chemotherapy. In mice, a diet without carbohydrates (or very little of them) appears to reduce the expression of MCL-1 in their tumors and thus improve outcomes .
Ketones are potent anti-inflammatory molecules. Inflammation, although essential to handle tissue damage and ward off foreign invaders, sometimes need to be dampened down. This is where ketones can shine.
Cancers are often associated with local and systemic inflammation. Dampening down inflammation at the right time and for the right target tissues, may be crucial to managing cancer symptoms as well as providing the immune system some respite so that it may better fight the cancer [13,14]. Maybe.
For more on how ketones can cleverly modulate inflammation, see our article How ketogenesis and ketones Treat Inflammation.
Gene regulatory changes
It would’ve been much more catchy to title this subsection “Epigenetics” but that would be wrong for reasons that are besides the point here. Suffice to say, ketones not only get used up for energy but they also regulate changes at the genetic level [15,16].
Some ketones, produced by fasting or by eating a ketogenic diet, can regulate changes in the expression of genes because they are a class 1 histone deacetylase inhibitor (HDAC1). HDAC1 has actual and potential roles in the treatment of cancer [17,18].
Hyperthermia: turn the heat up on cancer
Hyperthermia, also known as heat stress or thermotherapy when applied therapeutically, is thought to help treat cancers in ways not too dissimilar to the approaches discussed above. Essentially, the heat is also a stressor which cancer cells handle less well than healthy cells.
The NIH nicely summarizes the putative mechanism, saying ,
“Hyperthermia may make some cancer cells more sensitive to radiation or harm other cancer cells that radiation cannot damage. When hyperthermia and radiation therapy are combined, they are often given within an hour of each other. Hyperthermia can also enhance the effects of certain anticancer drugs”
It’s not too dissimilar to how elderly people handle the heat poorly compared to younger folk. Cancer cells are less heat resistant than healthy cells.
Medical case-reports can be the seeds germinating entirely novel approaches to treating disease as well as flashes in the pan leading to nowhere but Disappointment City. I hope what you take away from these 2 medical case reports is that metabolic strategies are worth learning about not only because their results are promising but because they touch on fundamental processes of biology with a wide breadth of application.
Have you used metabolic strategies to improve your health?
What diseases or health goals do you think these approaches could bear fruit for?
Let us know in the comments section and hit us up with more questions about all of this at https://ask.breaknutrition.com/
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