“I want people to live to be 110 healthy,” says Dr. Valter Longo, founder of Los Angeles-based L-Nutra, a new breed of tele-medicine startup backed by 25 years of scientific research. “It sounds like science fiction,” admits Longo “but it’s not.”
Silicon Valley players like Apple and Google are moving into healthcare. But L-Nutra is a taking a different approach, looking to “flip the script”.
Instead of treating age-related diseases like diabetes, cancer, and Alzheimers one by one, L-Nutra’s goal is to slow aging – and prevent or delay many age-related diseases – in one fell swoop.
Recently science has discovered that two of the most powerful aging pathways in the body are nutrient-sensing.
Which is why top anti-aging drug candidates in some way manipulate pathways that also are tightly wired to levels of protein and sugar in the bloodstream. Rapamycin interacts with mTor, Metformin interacts with the PKA, and NAD is a precursor to Sirtuins (whose levels also rise during fasting).
L-Nutra’s approach is using nutrition, or “nutri-technology”, to produce similar anti-aging effects.
“I think people are underestimating the powerful effects, and that’s both good and bad,” says Dr. Valter Longo.
Nutri-technology: the Biological Equivalent of a Computer Backup and Repair Program
The startup holds a patent on the concept “nutri-technology”, manipulating genes in the body via nutrient-sensing pathways to slow aging.
Autophagy (self-eating of damaged components in the cell) could play an important role in slowing the biological age clock. L-Nutra has developed a five-day protocol that works on the body’s nutrient-sensing pathways to flip the autophagy switch “on”.
But unlike caloric restriction, L-Nutra is a pulsing of caloric restriction followed by refeeding. For a healthy person this means being well nourished and eating well except for brief periods of ten to fifteen days throughout year.
L-Nutra’s product the ProLon fasting mimicking diet is a low-calorie plant-based meal plan consisting of soups, snack bars, and sports drinks and provides roughly 30% of your normal caloric intake (1,100 calories on Day 1 and on Days 2-5 750 calories.)
L-Nutra pilot clinical trial data shows a trend that the refeeding phase causes stem cell proliferation .
Bloodwork was used to measure circulating stem cells in L-Nutra’s pilot study. Muscle biopsies from participants are needed to figure out exactly what’s happening in regards to stem cell proliferation. Mesenchymal stem cells appear to play a role in tissues like the liver regrowing, but mechanisms of action aren’t well understood yet.
L Nutra’s origin story all begins with cancer.
Back in 2008, Longo realized cancer genes and aging genes are connected. His hunch was that the genes that control aging, are the same genes that get stuck in the on-mode in many cancers.
In a mouse-model clinical trial Longo’s team gave mice a high dose of chemotherapy. One group of mice was fasted, and one group was fed. A video shot by his lab shows mice in a fasted state after chemotherapy, moving about their cage normally. But mice in a fed state who received the same course of chemotherapy, appear exhausted and just lie down in their cages.
In this pilot study, only 35% of the mice receiving chemo in a fed state survived.
Cancer cells seem to be hyperactive, and need a microenvironment that will support growth.
Longo’s hypothesis was that if you deprive cancer of glucose and protein with fasting, the rapidly dividing cancer cells (which require more fuel than normal cells) will struggle.
When nutrients are scarce, normal cells go into a slowed down resting mode. But certain types of cancers may lack metabolic flexibility, and can’t switch over to a hunkering down mode that scientists call “quiescence”.
Scientists are also beginning to suspect that autophagy (which occurs during fasting) causes cancer cells to release ATP into the cytoplasm; and this process may trigger the body’s immune cells to move in to kill cancer.
But conducting a clinical trail to test water-only fasting with human cancer patients is not so simple. It took five years to enroll 18 cancer patients in a pilot study.
“It was a disaster,” admits Longo.
“So then we asked people what if we prepared a box of nutrition [with three meals] for a fasting mimicking diet?,” says Longo. “So you give the box to patients like medicine. And that’s when everything turned around.”
How Nutri-Technology Works: Cells Have Antennas and Do “Blebbing”
Cells in the body have nutrient-sensing antenna. This tiny organelle or tube that protrudes outside the cell, called a cilium, gives the cell information about its surrounding and enables it to respond.
Nutri-technology is about delivering calories to make fasting safer, but not enough to trigger your cell’s tiny nutrient-sensing antennas.
As ProLon Medical Liaison Dr. James Kelley explains the idea is to tell the body to switch from growth to repair mode. “Growth is good, but it can also lead to cells dividing more, and to a greater risk of mutations.”
ProLon down regulates three important aging pathways:
Insulin like growth factor (IGF-1) – a protein hormone that is similar to insulin in molecular structure. It is a big gene with a six-part axis of pathways that sends a “go-go” signal to the body to grow. IGF-1 responds to protein (especially animal protein) and drives up mTor. Low levels of IGF-1 are associated with a lower risk of cancer and diabetes.
mTor – or the “protein pathway” is a master regulator of autophagy, or cellular cleanup. mTor is activated by protein (and very strongly by animal protein) and carbohydrates. mTor seems to accelerate aging pathways and prevent the body from turning on tumor suppressing genes.
Protein Kinase A (PKA) – PKA or “the sugar pathway” is switched on by glucose and appears to regulate metabolism. This pathway can activate enzymes and regulate gene expression. If PKA is not controlled, it can lead to hyper-proliferation of cells and contribute and or lead to the development of cancer.
The effects of ProLon appear in the refeeding. “IGF-1 levels come back up after the fast,” which Longo says is an important “Part B” that is missing from caloric restriction.
So why five-days? “Believe me, if we could make the program less than five days, we would,” says medical liaison Dr. Kelley.
“Apoptosis is programmed cell death and begins somewhere around Day Four,” explains medical liaison Dr. James Kelley. “And by Day Five mesenchimal stem cells proliferate.”
On day five early pilot clinical trials show that mesenchimal stem cells increased by 800%, and go into standby mode.
MSCs can only be created in your body when IGF-1 and mTor levels are low. MSCs are multipotent stromal cells that are capable of differentiating into, and contributing to the regeneration of mesenchymal tissues such as bone, cartilage, fat, tendon, and muscle.
Mesenchymal stem cells have a unique feature, a “homing” mechanism.
Ketogensis is emulsification of fat, or the body using fat for energy. During ketogenesis autophagy occurs, where cells try to scavenger parts from other cells to repair themselves.
Apotosis is an intra-cellular program that causes a cell to kill itself after damage has occurred. Apotosis is one of the ways that multicellular organisms protect themselves from cancer.
“During apoptosis a cell decides it’s too damaged to try and repair itself, and essentially blows itself up,” says Dr. Kelley.
Without food and low mTor hormone levels circulating in the blood, the body goes from a catabolic (growth) to an anabolic (repair) mode and at the five day mark can make mesenchimal stem cells. These stem cells then use a “homing” beacon type of function to move from the bone marrow, to circulate in the blood.
Stem cells (in mouse model studies only) repaired pancreatic beta cells, which are important because they produce insulin in the body.
A biohack for aging in just five days sounds too good to be true.
The startup’s biggest challenge may be market education. ProLon gets confused with calorie restriction, intermittent fasting, and ketogenic diet (technically ProLon is a high-fat medical ketogenic plan).
The average person is not going to pick up a copy of the scientific journal Cell Metabolism and dive into a clinical trial. But they’ll enthusiastically follow the advice from a YouTube video “diet expert” (with no PhD in biochemistry).
ProLon was tested head to head against a keto diet in a clinical trial involving Multiple Sclerosis (MS) patients. Five days of ProLon produced similar effects to six months of a ketogenic everyday diet.
Any mention of fasting is usually met with rolled eyeballs. But clients are finding there’s just enough food to get through it.
“We’ve got NFL football players who say yes, I can do this,” says Longo. “We feel good about the efficacy, safety, and compliance.”
With headlines about contestants on the Biggest Loser complaining about regaining all the weight and more, a concern is that fasting (like crash diets) – won’t work. The trick, explains Longo is counter-intuitive:
“We are nourishing the body, while starving it.”
“Most people in our clinical trials have never gone a day without eating,” according to Longo.
Doctors as Beta Testers
“Eat your own dogfood,” as they say in Silicon Valley. In L-Nutra’s case functional medicine doctors (not a Big Pharma sales rep) recommend ProLon to their patients. And this is often after the doctors themselves have done a fasting mimicking diet (FMD).
“I had a diabetic patient who was trying to quit soda for a year, and couldn’t do it,” an endocrinologist who is also a ProLon client says “After one cycle of ProLon, he quit soda.”
ProLon customers get a one-on-one session with a health coach, to work through any emotional hurdles or questions about how to fast. Facebook Live fasting webinars provide helpful tips from doctors, ProLon’s own team of medical liaison’s, and fitness experts.
L-Nutra is also collaborating with a leading biogerentologist on an app to track biological age based on a blood test and 9 biomarkers.
“We can’t say if this (using ProLon) is reversing aging,” cautions Longo.
But as America faces a diabesity epidemic, Nutri-technology could be a solid science-backed biohack.
Longo’s research team hopes to publish results from a larger human clinical involving several hundred ProLon users, sometime in 2020.