Category Archives: Clinical Trials

Even Without Steroids, Cancer Patients Experience Less Chemo Side Effects on Fasting Mimicking Diet

In 1971 President Nixon declared a “War on Cancer”, and signed the National Cancer Act on December 23, 1971. Since the early 70s the focus in cancer research has been on drug development, as well as early preventative screenings.

But a somewhat eyebrow raising trend in cancer treatment, is exploring ways to treat certain cancers by combining standard of care therapies and nutritional intervention. Based on decades of aging research, nutritional pathways in the body are used in a targeted way to impact the cancer patient microenvironment and oncogenes. Early human pilot studies are testing whether a few days of fasting with food, followed by refeeding can make chemotherapy more targeted and less toxic.

A recent study investigated whether the fasting mimicking diet (FMD) influenced the toxicity or effectiveness of chemotherapy in women with early-stage breast cancer. The fasting mimicking diet is a four-day meal replacement designed to provide vital nutrients. The FMD triggers the body to switch from an anabolic (growth state) to catabolic (repair state) metabolism, and for cells to enter into a protected state.

The authors of the randomized controlled study assigned 131 women with stage II/III breast cancer to receive either a low calorie fasting mimicking diet or their regular diet three days before and throughout neoadjuvant chemotherapy.

Chemotherapy administered to shrink a tumor prior to surgery is known as neoadjuvant chemotherapy.

Researchers observed that women on the FMD were more likely to experience a 90 to 100 percent tumor cell loss as compared to women on a regular diet. Patients on the FMD had less DNA damage in T-lymphocytes from chemotherapy than those on the regular diet.

A fasting-mimicking diet (FMD) combined with chemotherapy resulted in a 300-400% increase in the chance of killing 90-100% of cancer cells in women with breast cancer. DNA damage in T-cells was less in patients who received the FMD with chemotherapy.

Interestingly, a steroid Dexamethasone was not given to the FMD group. But there was no difference in toxicity between both groups.

Dexamethasone is an antiemetic drug, belonging to a class of drugs that is effective against vomiting and nausea. Antimetics are typically used to treat motion sickness and the side effects of general anaesthetics and chemotherapy directed against cancer. Administering steroids is a standard practice to help chemotherapy patients stave off naseau and handle chemo side effects.

According to the study: “This suggests that the FMD may obviate the need for dexamethasone in the prevention of the side effects of chemotherapy. Importantly, DNA damage in T-lymphocytes was less in patients who received the FMD in combination with chemotherapy compared to those receiving chemotherapy while on a regular diet, suggesting that the FMD protected these cells against the induction of DNA damage by chemotherapy.”

Steroids like dexamethasone are routinely given to cancer patients directly following chemotherapy, but also can trigger serious spikes in insulin.

Typical cancer dietary guidelines encourage chemo patients to consume a high protein diet to combat malnutrition or muscle wasting.

Only normal weight patients were involved in this study to guard against cachexia or muscle wasting. Fasting faces the challenge of going against nutritional guidelines in cancer therapy that are deeply entrenched. And patient compliance in this study was problematic, indicating that patients may need to be followed carefully or supported by a dietician in future larger mult-site studies still in the planning stage.

For now, this pilot trial suggests that (for certain cancers) new nutritional as well as steroid administration options, could be on the horizon.

Diluting Plasma Slows Aging, New Mouse Study Suggests

University of California, Berkeley researchers have recently published a mouse model study that shows age-reversing effects can be achieved by diluting the blood plasma of old mice.

In 2005, University of California, Berkeley, researchers made a surprising discovery by stitching together a young and and old mouse like conjoined twins. Sharing blood and organs between the mice, scientists rejuvenated tissues and reverse the signs of aging in the old mice.

This conjoined twin mouse model study led to the idea that young blood contains special proteins, which deliver a ‘fountain of youth’ effect. And biohackers got the idea that getting transfusions from young donors aka “blood boys” could slow aging.

Problem is mouse studies are not a strong signal and exploratory. A follow on mouse model study conducted by the same research team, now shows simply diluting the blood plasma of old mice achieves age reversing effects.

Here’s how parabiosis became a thing:

Early 2000s – Senior researcher and professor of bioengineering Irina Conboy and Michael Conboy have a hunch that our body’s ability to regenerate damaged tissue remains with us into old age in the form of stem cells. But that somehow these cells get turned off through changes in our biochemistry as we age.

2005 – Conboy lab publishes study showing that making conjoined twins from the old mouse and a young mouse reversed many signs of aging in the older mouse. Many researchers seized on the idea that specific proteins in young blood could be the key to unlocking the body’s latent regeneration abilities.

2016 – a second follow-up study finds young blood does not reverse aging in old mice. Tissue health and repair dramatically decline in young mice when half of their blood is replaced with blood from old mice.

The study suggests to Irina Conboy that young blood by itself will not work as effective medicine. Rather the idea that emerges is that inhibitors in old blood could be a target to reverse aging.

In this 2016 study, Conboy and colleagues developed an experimental technique to exchange blood between mice without joining them so that scientists can control blood circulation and conduct precise measurements on how old mice respond to young blood, and vice versa.

In the new system, mice are connected and disconnected at will, removing the influence of shared organs or of any adaptation to being joined. One of the more surprising discoveries of this study was the very quick (within 24 hours) onset of the effects of blood on the health and repair of multiple tissues, including muscle, liver and brain.

June, 2020 – A new study finds that diluting blood in old mice by replacing half of the plasma with a saline and albumin mixture was able to reverse aging in the brain, liver, and muscle.

In a press release statement Irina Conboy, a professor of bioengineering at UC Berkeley who is the first author of the 2005 mouse-conjoined twins paper and senior author of the new study explains the results:

“There are two main interpretations of our original experiments: The first is that, in the mouse joining experiments, rejuvenation was due to young blood and young proteins or factors that become diminished with aging. But an equally possible alternative is that, with age, you have an elevation of certain proteins in the blood that become detrimental, and these were removed or neutralized by the young partners.”

In the years since the exploratory 2005 study, scientists have spent millions to investigate the potential medical properties of youthful blood with enterprises emerging to infuse old people with young blood.

“What we showed in 2005 was evidence that aging is reversible and is not set in stone,” Irena Conboy said in a UC Berkeley press release. “Under no circumstances were we saying that infusions of young blood into elderly is medicine.”

A Top Aging Biomaker, the Science Behind C-Reactive Protein

Measuring and charting C-Reactive Protein (CRP) values is proving useful in diagnosing Covid 19 patients.

But CRP could also play a role as an important biomarker, not only for infections, but successful aging. CRP is both a first responder in acute infections, and elevated in low-grade inflammation.

During an infection white blood cells including macrophages and T cells release a pro-inflammatory protein involved in cell signaling called cytokine interleukin-6. The activation of the interlukin-6 protein, then causes a downstream rapid increase in CRP levels in the blood.

CRP is an “acute phase reactants”, and part of the first responder part of the immune system. CRP works in part by binging to a dead or dying cells, and clearing away these pathogens and dead tissue.

The half-life of C-reactive protein is short.

Due to its rapid response C-reactive protein levels can spike up to 10,000-fold in a matter of hours.

When it was first discovered in 1930, scientists thought this ring-shaped blood protein might be a pathogenic secretion since CRP protein is elevated in a variety of illnesses, including cancer.

The High Sensitivity C-Reactive Protein Biomarker in a Brief Timeline:

1993 – William Ershler, in his article “IL-6: A Cytokine for Gerontologists,” indicated IL-6 as one of the main signaling pathways modulating the complex relationship between aging and chronic morbidity. IL-6 in human physiology and pathology has substantially grown. Low Vitamin-D, slower gait speed, and increase in Interlukin-6 are parameters studied in gerontology field. However, measuring Interlukin-6 levels was reserved for clinical trials, due to the expensive blood test.

Mid-1990s – In the mid 1990s, immunoassays for C-reactive protein (CRP), with greater sensitivity than those previously in routine use, revealed that increased CRP values, even within the range previously considered normal, strongly predict future coronary events. These findings triggered widespread interest, especially, remarkably, in the US, where the clinical use of CRP measurement had been largely ignored for about 30 years.

2002 – Data suggesting that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol roils. Scientists conducting a large population study in a New England Journal of Medicine 2002 found that many things can cause elevated CRP, making the blood test not a very specific prognostic indicator. But CRP deliver additive value at providing more information on risk for cardiovascular events than the LDL cholesterol level alone.

2009 – Upstream of C-Reactive protein, Interlukin-6 Serum (IL-6) levels are studied in the clinical setting by gerontology researchers. In a gerontology cohort case study (because of its activity across multiple physiological systems), Interlukin-6 Serum levels were found to predict frailty with aging. The IL-6 pathway is named a “gerontology biomarker” as it appears to be profoundly implicated in the pathophysiology of physical function decline and chronic diseases that often affect older persons.

2018 – C-reactive protein added as one of reliable biomarker of 9 aging biomarkers in a new biological age clock. The new biological age clock called DNAm PhenoAge, looks beyond tissue samples to include immune system function.

The nine biomarkers that identified “phenotypic age” included: albumin, creatine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count.h.

On the heels of Covid, hsCRP is coming into the spotlight and could be a multipurpose biomarker of successful aging.

Clinical Trials: There’s an App for That

With so many whizzy fitness apps out there, there’s lots of tech today designed to get us fitter and optimized.

Now scientists are getting in on the act.

Big tech players like Apple grab the headlines, when it comes to testing out mobile devices to develop digital health strategies. Launched back in 2017 the Apple Heart Study explored the performance of the Apple Watch’s heart rate sensor and accompanying algorithm in detecting potential arrhythmias.

Digital trackers have led to little change in rise in chronic illness.

So behind the scenes scientists at the lab bench are building their own apps. The idea is to design an easy-to-use app to help do the heavy lifting of clinical trials, recruit patients, and gather better data.

A typical clinical trial funded by the National Institute of Health (NIH) can take up to five years. Mobile apps might help cut red tape.

Nutritional studies struggle to get patients to keep accurate food logs. Or nutrition research is criticized for not being tech savy or data-driven, but instead using general epidemiological studies.

A smartphone picture doesn’t lie. And apps could bring accurate data to nutrition studies which are typically overshadowed by drug discovery research.

But while this app looks like a fitness tracker, the endpoint isn’t weight loss or a faster running time.

Used by the research team at the Salk Lab in La Jolla, California which studies circadian rhthyms, myCircadianClock is designed for accurate data exchange between patients, doctors, and scientists.

The data is being used in time restricted (TRE) studies, and now with diabetic and hypertensive patients.

“We were surprised, people are not shy about taking photos of what they just ate for breakfast,” explains lead researcher Dr. Satchin Panda.

Going loud on social media with photos capturing your to-die-for-brunch is the new normal. And for scientists who study nutrition-sensing aging pathways, exploiting this mobile device activity could prove a boon.

By using apps chronobiology researchers hope to play the tech game to their own advantage. Because the alternative seems to be watching clinical research drown in a sea of broscience on intermittent fasting on social media.

Recently scientists wanted to know what would happen if patients ate in a ten hour window, in conjunction with taking medicine to treat cardiometabolic disease. The study was designed to use the mycircadian app to study the impact of time restricted eating (TRE) as an “add on” to statin and hypertensive medications.

The study used the myCircadianClock app to track how a ten-hour time -restricted eating window could reduce weight, blood pressure and even help treat hypertension and diabetes.

This app used the clinical setting is not about having patients post their six-pack abs to Instagram. Rather what the Salk Lab team tracks is a “feedometer”.

The “feedometer” is plot graph using the iphone photos, of exactly when meals happen.

According to Satchin Panda, many participants said that they were eating in a twelve hour window. But the “feedometer” smartphone photo plot graph, reveals that many of us eat in a fifteen hour window.

The app looks like any fitness tracker, but the science behind myCircadianClock involves decades of research.

Two major aging pathways mTor and PKA are both nutrient-sensing. Manipulating these nutrition-sensing some scientists believe, could be like hitting an epigenetic power switch.

Doctors treating diabetes and hypertension do not typically talk to their patients about using time restricted eating (TRE). But just because eating in a ten hour sounds simple, doesn’t mean it can’t turn off genes.

“The circadian system is a pillar of health,” says researcher Emily Manoogian “that has been for far too long ignored.”

Nutrition studies powered by smartphone photos are still in their infancy. But as tech-savy clinical trials continue to deliver results, time restricted eating could be an add-on to standard of care for cardiometabolic disease.