We recently had the chance to catch up with Dr. Kelly Gibas, a functional medicine practitioner (CFMP), licensed therapist (LPCC), and founder of Bristlecone Medical. We discussed a variety of compelling topics, including the promising early findings for her research around the ketogenic diet and Joovv’s full-body light therapy devices. Check out the exciting overview of what they’ve discovered so far.

What is your clinical & professional background, and what interested you in studying red light therapy?

I am a functional medicine practitioner (CFMP) and licensed therapist (LPCC) with advanced, doctorate training in pathologies of metabolic physiology including: metabolic syndrome, diabetes, polycystic ovary syndrome (PCOS) and comorbid central nervous system/autonomic deregulations: depression, anxiety, dysthymia and postural orthostatic tachycardia syndrome (POTS). In addition, I am an undergraduate Professor for junior/senior students who are applying for graduate programs in medicine (MD/DO, PA, NP, OT & PT); I also teach Human Physiology in the Physician Assistant Program.

I enjoy translational research; keeping one foot in clinical application and the other foot in academic research allows me to share both disciplines with my students. My research with red light therapy has its epicenter in a Clinical Trial (ClinicalTrials.gov Identifier: NCT03859245) Photobiomodulation & Ketogenic Diet for Treatment of Mid-periphery Retinal Disorders for Alzheimer's Disease Prevention, where I am exploring the impact of photobiomodulation (PBM) at frequencies of red (660nm) and near-infrared (NIR) (850nm), concurrent with a ketogenic dietary protocol (serum ketones @ .5 - 2.0mmol/L) to mediate vascular features of diabetic retinopathy (DR), diabetic macular edema (DME), age- related macular degeneration (AMD), mid-peripheral drusen formation, visual acuity and retinal disorders.

Red light therapy is fascinating because it is a powerful, non-invasive modulator of metabolism that is accessible/affordable to the masses with proven clinical application; unlike the common “Band-Aid” pharmaceuticals that mediate surface complaints at the expense of deeper pockets of puss, red light therapy, using clinical grade devices, like Joovv, that deliver the proper frequency, power & luminance, boost metabolism and increase energy production (ATP) via organic shifts in the function of the mitochondria.

Why do you find it compelling to study red light therapy and the ketogenic diet for hormone health in particular?

Red light amplifies the effects of a ketogenic diet by increasing metabolic flexibility, the ability for cells to efficiently burn both sugar and fat.

Among the key features of metabolic pathology is “stiffness" in mitochondrial substrate selection. Cells fail to flux their fuel choice in response to changing energy demands. Normal energy metabolism is characterized by periodic shifts between glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels. The crosstalk and cooperation between the competing substrates enables the mitochondria to choose the energy source that is most appropriate for a particular physiological state, thereby preventing both hyperglycemia and hypoglycemia.

Human physiology evolved to cope with dramatic fluctuations in energy supply and demand during periods of feast and famine (hunting/gathering). Episodes of refueling were typically preceded by sustained periods of energy deficit (fasting); most recently, this flexibility has been characterized as shifts between two primary nutrient sensing pathways mTOR (anabolic growth) and AMPK (catabolic breakdown). In stark contrast, physiology in the modern era is characterized by a steady influx of competing fuel sources. Over-nutrition and unabated substrate competition leads to states of metabolic insensitivity/inflexibility, characterized by over-activation of mTOR with distorted nutrient sensing, blunted substrate switching, and impaired energy homeostasis.

In the context of chronic over-feeding, the competition between substrates escalates, cooperation is lost, and the mitochondria are left in a state of indecision characterized by persistent oxidation of all three major fuels. The result is metabolic congestion.

Red light alleviates metabolic congestion by focusing its luminance on the mitochondrial machinery of the cell to amplify the action of cytochrome oxidase (COX) in the electron transport chain.

Because insulin mediates metabolic congestion by orchestrating the body’s flux between glucose, fatty acids, and amino acids, resistance to the action of the insulin causes aberrant nutrient partitioning. The onset of insulin resistance typically occurs early in the etiology of disease. The COX enzyme aids metabolism by pairing high-energy electrons (chemical byproducts of digestion) with oxygen to be neutralized into water. This is an important step in the synthesis of energy (ATP). But like the iconic I Love Lucy Chocolate Factory episode, if the COX enzyme looses synch with the flow of electrons; the high-energy electrons slip from their metabolic “track" forming dangerous free radials or ROS (reactive oxygen species), rather than being neutralized into water.

Red light supports increased flexibility by regulating the healthy expression of the COX enzyme for efficient fat oxidation.

The ketogenic diet is antithetical to the overfed phenotype. Dietary Ketosis sensitizes cells to the action of insulin by simulating a “mock fast” in the mitochondrial machinery via the activation of AMPK. AMPK increases metabolic flexibility, reduces carbon combustion and helps to clear metabolic congestion.

Could you provide a brief overview of the hormone-related study involving Joovv light therapy and the ketogenic diet? How would you characterize the results so far, in general?

Preliminary results show red light therapy in the context of serum ketones > .5 mmol/L, increased the healthy expression of primary sex hormones in both men and women; likewise, serum progesterone increased in pre & post menopausal women showing improved synthesis of adrenal DHEA.

Method:

Male and female participants > 18 years of age were given a free 12-week intervention protocol through Bristlecone Medical in Maple Grove, Minnesota. Participants were randomly divided into two groups. A clinically prescribed ketogenic diet (KD) was provided for group A; the other group (B) maintained their current standard American diet (SAD). Members of both groups (A/B) participated in PBM therapy, 4-5 days per week, utilizing a combination of the Joovv Elite and Joovv Solo NIR/red light systems.

Serum hormone levels were assessed on all participants pre-/mid/post intervention. Total testosterone/free testosterone levels were measured for men; progesterone/estradiol levels were assessed for women. Pre-menopausal women were assessed during the luteal phase of the menstrual cycle on days 19-21.

Results: The preliminary results reflect approximately 50% of participants who completed the 12-week intervention. Remaining participants are approximately six weeks to completion based on start date. Women: Progesterone levels increased in post-menopausal and pre-menopausal women in both groups; however, the keto group reflected a greater degree of change. The preliminary results suggest the zona reticularis of the adrenal cortex increased endogenous production of DHEA & progesterone resultant of PBM offering energetic, regulatory support to the adrenal mitochondria.



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You stated that the initial female results suggest the innermost layer of the adrenal cortex increased progesterone significantly, offering healing support to the adrenal glands. Why is this significant?

Red light therapy together with the ketogenic diet modulate the stress-related changes in steroidogenesis via the regulation of key mitochondrial enzymes and signaling pathways leading to reduced activation of the HPA axis, reductions in serum glucose and serum insulin levels with increased synthesis of DHEA and progesterone.

In addition to manufacturing cortisol and adrenaline, the adrenal glands synthesize the steroid hormone DHEA, known chemically as dehydioepiandrosterone. DHEA plays several vital roles in health, including the metabolism of cholesterol to make the sex hormones progesterone, estrogen and testosterone. As men and women age, levels of DHEA in the body naturally diminish, along with the synthesis of the sex hormones. Low progesterone affects both peri-menopausal and post-menopausal women. This decline in DHEA and sex steroids is a function of mitochondrial decline.

Progesterone is a sex hormone synthesized both in the ovaries and from DHEA by the cells of the zona reticularis in the innermost layer of the adrenal cortex; low levels of DHEA contribute to the comorbidity of adrenal insufficiency and estrogen dominance common to middle-aged, peri-menopausal/post-menopausal women. As ovulation declines, women rely on the adrenal production of DHEA to sustain progesterone levels to prevent estrogen dominance.

Adrenal insufficiency refers to a common condition in which high levels of sustained stress diminish the proper functioning of the adrenal glands by decreasing the synthesis of the adrenal cortex steroid hormones synthesized in the mitochondria. Pregnenolone, derived from cholesterol, is the precursor for mitochondrial steroidogenesis; elevated secretion of cortisol caused by acute or chronic stress inevitably results in a lower production of DHEA and progesterone.

While a rise in cortisol levels and a concomitant drop in DHEA/progesterone are clinical characteristics of early and mid-stage stress progression, research shows this phenomenon is not caused by a diminished availability of pregnenolone, or the "pregnenolone steal” as previously assumed. Cortisol synthesis does not shunt pregnenolone away from other hormone pathways; rather, cortisol indirectly inhibits the synthesis and secretion of DHEA/progesterone via stress signaling pathways resulting in the pathophysiological changes related to stress.

Research shows that intra-adrenal depletion of pregnenolone is not the cause of adrenal insufficiency as once thought; rather, the fundamental reason for decline in the conversion of cholesterol to pregnenolone occurs in the mitochondria of the cells in the adrenal cortex zona fasciculata that are responsible for the synthesis of the hormones. Decades of research on steroidogenesis show the control of adrenal hormones is regulated by cell-specific enzyme concentrations and external signals coming from outside the adrenal gland The HPA axis and subsequent cortisol synthesis/secretion is related to reduced DHEA production, but this relationship is tightly facilitated by regulatory processes (feedback inhibitions, receptor signaling, genomic regulation of enzymes).

Experimentally induced hyperglycemia and hyperinsulinemia have been shown to down-regulate DHEA and progesterone production in human subjects. Additionally, cell-culture studies suggest that under chronic inflammatory stress, the zona reticularis down-regulates DHEA production when ACTH is elevated. Regulatory signaling and enzyme activation are driving forces affecting the dynamic flux between cortisol and DHEA/progesterone/estrogen/testosterone.

Red light therapy and nutritional ketosis mediate inflammatory stress and regulate the healthy production of DHEA, while suppressing the HPA axis.

You noted that the ketogenic diet group of women experienced a greater trend in degree of change (17%) in estradiol. Why does increased estradiol matter and what impact will this have on women’s health?

Recent studies cite estrogen as a master regulator of female metabolism modulating fuel flux in peripheral and cerebral tissue. Plummeting levels of 17B-estradiol (E2), common to menopause, is potentiated as an early risk biomarker for late-onset Alzheimer’s disease (LOAD) in women.

Female ovarian production of 17B-estradiol (E2) represents the youthful, regulatory expression of estrogen; E2 modulates the female menstrual cycle ensuring the healthy release of the corpus luteum. The corpus luteum secretes progesterone, which is ultimately responsible for the decidualization of the endometrium and maintenance of a healthy uterine lining. With insufficient expression of E2, menstrual cycles become anovulatory; without the release of the corpus luteum the synthesis of progesterone dramatically falls. This drop in progesterone results in estrogen dominance and increases the risk for sex-linked cancers of the breast, ovary and colon.

As lipid hormones, sex steroids diffuse the blood-brain barrier regulating cerebral metabolism by modifying nuclear DNA. In particular, 17B-estradiol holds unique transcriptional potential to partition fuel and orchestrate metabolic flexibility thereby preventing sudden energy deficits. Similarly, both testosterone and 17B-estradiol enhance mitochondrial ATP via coordinated responses from mitochondrial enzymes, leading to optimal cerebral glucose metabolism.

In peripheral tissues, E2 protects women against adiposity, insulin resistance and Type II Diabetes (T2DM) by modulating caloric intake with energy expenditure via the Ventromedial Nuclei of the hypothalamus. Declines in the peripheral steroidogenesis of 17β-estradiol, progesterone and testosterone are major features of aging and disease.

You also tested testosterone levels in men. Can you comment on the preliminary results for both the ketogenic diet and SAD groups?

Recent studies confirm that a 12-week ketogenic diet increases testosterone in men via the bioavailable increase in cholesterol and DHEA; likewise, red light therapy improves the mitochondrial synthesis of testosterone from DHEA.

Across the board, the male participants who completed the 12-week intervention reported increased/restored testosterone levels. These results are consistent with previous reports showing that both red light therapy and the ketogenic diet are endogenous boosters of testosterone.

In the male population, testosterone adaptively converts to estradiol (E2); however, healthy levels of testosterone provide a hormonal challenge to the synthesis of E2 keeping the testosterone/estrogen ratio in balance as to avoid symptoms of male-patterned estrogen dominance such as enlarged prostate and

Testosterone in men is similar to progesterone; healthy levels of testosterone provide adequate challenge to the proliferative effects of E2.

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From your perspective, what are the implications of these results (for both men and women) on the broader healthcare community?

Red light therapy and dietary ketosis are anti-inflammatory.

Photobiomodulation (PBM) at frequencies of red (660nm) and near-infrared (NIR) (850nm) and the oxidation of ketone bodies have the unique ability to repress the release of ACTH and inhibit the HPA axis. Using fat for fuel activates AMPK and stimulates the epinephrine pathway in the adrenal medulla representing an adaptive response to stress; as previously discussed, red light therapy accentuates beta oxidation in the mitochondria.

Additionally, cell-culture studies suggest that under chronic inflammatory stress, the zona reticularis down-regulates DHEA production when ACTH is elevated. Inflammation is a driving influence affecting the dynamic relationship between cortisol and the synthesis of DHEA/progesterone/estrogen and testosterone levels.

Recent studies of poorly controlled Type 2 Diabetics (T2DM) with elevated cortisol and low serum DHEA showed inhibition in the enzyme responsible for the synthesis of DHEA in the zona reticularis. After six months of a glucose/insulin lowering diet, enzyme activity was restored along with near normalization of cortisol, DHEA and progesterone levels.

Are there any patient stories that really stick out to you? How would you describe the patients’ reactions to Joovv treatments?

We have witnessed several inspiring stories during the 12-week intervention periods. Two patients stand out, in particular:

A peri-menopausal woman who reported a dramatic increase in her libido and positive effects on her long-term marriage.

A 30-year old obese diabetic with a deep lower leg ulcer that was unresponsive to traditional modes of healing; the ulcer gradually reduced in depth and breadth, while using the red light therapy and maintaining dietary ketosis @ serum ketones > .5 mmol/L.

Are there other patient populations that you’d like to study red light therapy with, and why?

I strongly believe red light therapy, together with a clinically prescribed and monitored ketogenic diet, are powerful healing agents for the prevention of diabetic ulcers and lower extremity amputations.

Diabetic ulcers commonly result in lower limb amputations in long-term diabetics. The prevalence of diabetic foot ulcers and lower extremity amputations are escalating due to earlier onsets of T2DM.

Diabetic ulcers are resultant of damaged vasculature; unhealed wounds are a significant public health concern as the post-amputation, mean survival rate in diabetics is only 5 years. This statistic points to the drastic need for prevention, early detection and proven treatments for lower limb ulcers in the diabetic population.

Photobiomodulation has been shown to increase circulation and significantly increase perfusion of the skin. The increased perfusion resultant of PBM indicates that the improvement in blood flow is coupled with an increase in trophic components delivered to the skin.

Why does it matter to find natural, non-invasive and non-pharmacological ways to treat illness?

Red light therapy and clinically prescribed ketogenic diets are disruptive innovators in a reactionary system of healthcare. These innovative modes of treatment harness the potential to move the needle of healthcare away from reactionary prescribing and toward preventative restoration of both lifespan and health-span.

Access for the masses to optimized care at affordable rates is desperately needed. Current studies prove that numerous people with full insurance coverage fail to adhere to prescribed medical protocols; drugs are not taken and appointments are unattended. This negligence by fully insured patients, coupled with the patients who are inadequately covered, creates an increasingly heavy burden on the system as untreated, chronic diseases quickly progress into critical, end stage care.

Natural, non-invasive and non-pharmacological modalities of care provide treatment options that are preventative in nature as well as affordable/accessible to the masses; like red light therapy, natural treatments are done in the comfort of the patients’ home and delivered via a dose-dependent manner focused on prevention.

For more information about Dr. Kelly Gibas’ clinical trials, current research and projects, click here.