Effective Strategies for Healthier Skin

Follow these guidelines and you’ll have significantly improved skin. These recommendations are geared towards lowering inflammation, improving insulin sensitivity, and reducing oxidative stress, which are the hallmarks of acne sufferers. Do not fall into the temptation of believing that acne is solely caused by genetics. Studies of groups of people living a non-western lifestyle show zero acne, and when those same groups westernize they get acne and all other inflammatory conditions (heart disease, acne, rosacea, etc).

81% of acne patients suffer from insulin resistance, according to this study. From another study: “These results suggest that insulin resistance may have a role in the pathogenesis of acne.” A third study shows that fasting insulin and insulin resistance (HOMA) are nearly double in acne patients.

Oxidative stress markers are all elevated in acne patients according to this study. From another paper: “The results obtained in this study clearly showed the existence of oxidative stress in patients with acne vulgaris, and that oxidative stress along with inflammation play a critical role in acne pathogenesis”

Inflammation markers are higher in those with acne: In the study referenced here, patients with severe acne had 3x the cRP (C-reactive protein, an inflammation marker) as those with moderate acne. This study shows the inflammatory markers IL-8 and IL-17 are elevated in acne patients. This study found that the inflammatory marker TNF-α (Tumor necrosis factor alpha) is elevated in acne patients. Acne patients also had higher levels of triglycerides and LDL cholesterol. This study found significantly higher SII (systemic immune-inflammation index), white blood cell count, platelet count, neutrophils, monocytes, platelets, and PCT (procalcitonin) in acne sufferers. All indicating an overactive immune system.

The techniques below will improve your insulin resistance, inflammation, and oxidative stress.

  • Diet has a profound impact on acne. Individuals consuming a natural, anti-inflammatory diet rarely suffer from acne. Focus on a low glycemic index diet rich in vegetables, fruit, and wild fish, with limited meat. Avoid foods cooked in vegetable oils (canola, soy, palm, safflower, or sunflower oil), opting for olive, avocado, and coconut oils instead. Drink large amounts of water and avoid salt. Avoid sugars and processed foods entirely. Keep your net carb intake (total carbs minus fiber) under 30 grams daily until your skin improves. Steer clear of flour, dairy, rice, grains, sugar, and alcohol. Processed foods should be avoided. Aiming for two or three meals a day while not snacking can help minimize insulin spikes. Eating meals earlier in the day, during daylight hours, is also advised. The Whole30 diet is an effective frameworks to explore. Many studies have shown that high glycemic load diets (those that rapidly raise blood sugar) and dairy (milk) are associated with worse acne. Some studies suggest that a diet rich in omega-3 fatty acids may help reduce acne severity. Vitamin A, found in foods like sweet potatoes, carrots, and spinach, has been shown to benefit skin health. From another study: “Consuming vegetables, legumes, oily fish, olive oil, and nuts, and limiting meat, cheese, and alcohol appear to be beneficial for both acne and rosacea.”. Try to consume foods rich in AMPK activators, polyphenols, spermidine, mtor inhibitors.
  • Don’t eat leftover meat or fish. Histamine and bacterial buildup can begin almost immediately after storing food in your refrigerator. After a day or two, this buildup may present a problem for some individuals. While this issue is more commonly associated with rosacea, acne sufferers may also want to take precautions to minimize potential triggers.

From a study documenting subjective assessments of dietary patterns and acne:

  • Take a 20-minute walk after every meal to combat insulin resistance and avoid blood sugar spikes. Walking after every meal can improve insulin sensitivity by up to 30%. You will not find an easier and more effective health hack than walking for 20 minutes after every meal to improve your insulin resistance.

  • Eat meals in the following order. First, consume vegetables and fiber-rich foods; second, eat proteins and healthy fats; and last, carbohydrates. Combining this eating style with a light walk after meals may help lower insulin and blood sugar spikes and improve your insulin sensitivity over time. Improved insulin sensitivity and lower insulin levels may contribute to many skin benefits, including a reduction in excess sebum production, which is a primary factor in acne development. The Glucose Goddess Instagram account offers helpful tips and information on this topic: https://www.instagram.com/glucosegoddess.

  • Consume several servings of fermented foods per day. This study showed that eating fermented foods lowered the levels of 19 inflammatory proteins, including Interleukin 6. Some options include:
    • Fermented vegetables (like carrots, beets, and radishes, made without added salt or sugar)
    • Raw sauerkraut (made without added salt or sugar)
    • Kimchi (made without added sugar or fish sauce)
    • Pickles (made without added sugar or salt, using a salt-free pickling process)
    • Unsweetened, unflavored kombucha (homemade or store-bought)
    • Tempeh (made from soybeans, without added salt or sugar)
    • Miso (choose low-sodium varieties)
    • Natto (made from fermented soybeans, without added salt or sugar)
    • Sourdough bread (made without added sugar or salt)
    • Apple cider vinegar (raw, unfiltered, and unpasteurized)
  • Avoid insulin spikes and blood sugar spikes, and keep your fasting blood sugar low. Your blood sugar stays healthy when you eat a low glycemic index diet, avoid snacking in between meals, and walk after meals. Most importantly, do not eat a large amount of high glycemic index foods in one sitting. HbA1c, or glycated hemoglobin, is a blood test that provides an average of your blood sugar levels over the past two to three months. This study showed higher hba1c levels in acne patients than controls: “Acne patients were more likely to have prediabetes (HbA1c ≥ 5.7%) versus controls (22.8% vs. 11.3%, respectively”, p < 0.001).” You can use a CGM to measure your blood glucose or get bloodwork to measure your fasting blood glucose and hba1c.
  • Blood sugar spikes cause inflammation and oxidative stress. From this abstract: “Both lower glucose values and insulin therapy seem to be anti-inflammatory, whereas hyperglycemia (high blood sugar) increases the proinflammatory process and negatively affects the innate immune system”. This study showed that “Inflammatory Cytokine Concentrations Are Acutely Increased by High Blood Sugar”. And this is yet another study showing that inflammatory cytokine are acutely increased by high blood sugar.
  • A tablespoon of Apple Cider Vinegar before a meal will reduce your blood sugar spikes.
  • Supplements + oral medications: Clinical studies have demonstrated that Metformin, NAC, Zinc (75mg/day), Vitamin D, Turmeric/Curmumin, Milk Thistle, Selenium, Magnesium Threonate, a daily probiotic, and Vitamin B5 can significantly reduce acne. Avoid birth control and biotin. Biotin causes acne in many people. Metformin will require a prescription, which you can get at agelessrx. Take zinc with food or you will experience nausea. Antibiotics are an effective option, but they quit working after several months and can do unpredictable damage to your biome. If you cannot get acne-free, consider pausing all supplements and medications not recommended here. Here is a complete list of acne supplements to take with research backing each.

Sebum Regulation and Anti-Inflammatory

Vitamin D 2000 IU (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580068)

AMPK activator 

Berberine 400mg

Metformin (get via prescription at agelessrx.com)

Reduce Mtor

Sulforaphane 35 mg

Resveratrol (200 mgs)

Epigallocatechin Gallate (ECGC) (100mg)

Produces zinc superoxide dismutase, free radical scavenger / antioxidant

Zinc 50 mg

Copper 1.5 mg

Antioxidants

Milk Thistle (70 miligram)

Nicotinamide 250mg

Selenium (100 microgram)

NAC (1200 mg/day orally)

Glutathione (200mg/day)

Reduces testosterone/androgens

Spearmint (400mg) (reduces testosterone/androgens)

Metabolizing free fatty acids in blood stream and reduce sebum production

Vitamin B5 (panthathonic acid)

Probiotics

Lactobacillus acidophilus (2 billion CFUs)

Lactobacillus rhamnosus SP1  (2 billion CFUs)

Bifidobacterium longum  (2 billion CFUs)

  • Topical medications. Tretinoin + Azelaic Acid: Tretinoin will reduce acne but can worsen rosacea. Use azelaic acid instead of tretinoin for those with red skin or visible red capillaries. Azelaic Acid is equally effective in treating acne without the side effect of making skin red and irritated. With tretinoin, there will be an initial “purging” period in which you aggressively break out. Clindamycin is a topical antibiotic that is very effective in treating acne, but loses efficacy after several months. With a healthy lifestyle, you should have perfect skin while only using tretinoin and metformin and bypassing oral and topical antibiotics.
  • Sleep with mouth tape to avoid mouth breathing. Mouth breathing causes oxidative stress, according to this study. Breath with your mouth closed when you exercise and at all times during the day. HostageTape.com is excellent. If you find yourself mouth breathing (or stressed), consider hiring a breath coach such as Vince Dickson
  • Sleep: Getting enough sleep is beneficial for your skin, while a lack of sleep is a proven cause of acne. This study showed that sleep inconsistency is significantly associated with inflammation, and this study showed that short sleep is significantly associated with insulin resistance.  In 2015, a French study demonstrated that there is a strong correlation between acne and fatigue upon waking (i.e., poor sleep quality)

    To improve your sleep and manage its impact on health, aim for over 8 hours of rest nightly, maintaining a consistent and early bedtime. Avoid alcohol, as it significantly disrupts REM sleep, even in small amounts. Consider using blue-light-blocking glasses or dimming lights in the evening. Tracking devices like the Oura Ring can help optimize your sleep quality. Enhance sleep further with strategies such as using a dry sauna before bed, seeking ample daylight exposure (especially around 9 am and 12pm), meditating in the evening, turning off electronics by 10 p.m., avoiding stress and not eating within 4 hours of bedtime. Consider supplementing magnesium, selenium, inositol to improve sleep quality.

    This video provides excellent tools from improving your sleep quality: https://www.youtube.com/watch?v=h2aWYjSA1Jc

  • From “Strategies for Reducing Oxidative Stress: “Sleeping and Melatonin Production: Melatonin is produced primarily during the daily period of darkness, with only small amounts being synthesized during the day. For this reason, people should sleep long enough and in complete darkness in order to produce necessary amounts of the endogenous powerful antioxidant melatonin [1, 2] and benefit from its particular role in the protection of nuclear and mitochondrial DNA [3]. Melatonin is an antioxidant that can easily cross cell membranes and the blood-brain barrier [4]. Melatonin is a direct scavenger of OH, O2 −, and NO”. You cannot produce sufficient melatonin at night without spending a large portion of your day outdoors.
  • Perfect oral health: Brush, floss, and waterpik after each meal. Use a tongue scraper. Get cleanings 3-4x a year. According to this study, poor oral health causes inflammation.
  • Maximize time outdoors: To regulate your melatonin cycle, spend more time outside during the day. Spend your time in the shade, not in direct sunlight. Go for a 30-minute walk as soon as you wake up and another at noon. Avoid exposing your skin to the sun — walk in the shade! Your eyes require exposure to unobstructed sunlight in order for your pineal gland to suppress melatonin during the day, which causes a melatonin spike at night and a corresponding surge in Zinc Superoxide Dismutase, an enzyme that removes ROS (reactive oxygen species). I also recommend blasting your body (cover your face) with direct sunlight at least once or twice a week.
  • You must avoid blue light at night to get a sufficient melatonin surge when you sleep. A huge melatonin surge is a key to great skin. Do not use your phone or a computer after the sun goes down, particularly within an hour of bedtime or while in bed. When your eyes are exposed to blue light at night, your pineal gland reduces melatonin production during sleep. Melatonin production while you sleep is a crucial factor in achieving better skin. Melatonin is a precursor to copper-zinc superoxide dismutase, an enzyme that removes free radicals from your skin. If you don’t experience a proper nighttime melatonin surge, your immune system may attack your own skin cells to deal with the free radicals. Keratinocytes produce superoxide anions as an immune response when exposed to Propionibacterium acnes. Once superoxide anions (O2-) have completed their job, superoxide dismutase catalyzes their destruction. If this process fails, excess O2- will kill skin cells, leading to inflammation and the blockage of the sebaceous glands, which can contribute to the development of acne.
  • Inject Epitalon to improve your nighttime melatonin spike and improve your skin. You can buy Epitalon at www.peptidesciences.com or from a local peptide doctor. Melatonin is one of the most powerful antioxidants known to man and a nighttime melatonin surge is incredibly good for your skin.
  • No coffee, no caffeine, no nicotine: If you can’t cut out coffee altogether, drink less and drink it earlier in the day. Green tea, while still problematic, is less likely to cause acne and rosacea than coffee and is an easier switch than a full decaf life. Stimulants induce stress, increase sebum production, and make it harder to get great sleep consistently. Many people simply cannot solve acne while drinking caffeine. This study shows that “Caffeine increases cortisol secretion“ in people at rest or undergoing mental stress”.
  • Avoid stress. According to this study, “Cortisol (stress) causes an increase in sebaceous gland activity, and elevated levels of cortisol in stressful situations are manifested by increased sebum secretion“. Spending time outdoors can lower cortisol levels. This study showed that spending 20 minutes in a nature setting was associated a large drop in cortisol levels.

  • Reduce sebum on skin by lowering IGF-1, cortisol, and insulin: Acne and Rosacea patients produce 30-60% more sebum. Insulin and IGF-1 are both linked to elevated sebum production and acne. According to this study, “As expected, the subjects with acne had more (59%) sebum than the control subjects” If you are producing excess sebum, you have not solved the underlying cause of your acne. In the chart below, AG = acne group, ACG = acne control group, RG = rosacea group, RCG = rosacea control group.

  • Pause your existing supplements and medications: If you can’t get clear, consider switching or stopping all of your medications and supplements. A considerable portion of this site’s traffic comes from people on new medications who experience new and prolonged acne outbreaks. Supplements and medications cause acne as a side effect in a surprising number of people. Going to a zero medication/supplement as an elimination experiment is a worthy experiment.
  • Birth control causes acne in an estimated 20% of users. Progestin-only birth control can have unpredictable effects on acne, but more often than not, it increases it. If you are taking birth control and experience acne, consider switching birth control or pausing it altogether.
  • Multi-day fasting: Valter Longo’s work has shown that five-day fasts can permanently improve biomarkers associated with acne such as IGF-1, C Reactive Protein, LDL cholesterol, triglycerides, systolic blood pressure, and fasting blood glucose. According to this study, after completion of five-day prolon fast cycles, subjects in the fasting group reported an improvement in many aspects of skin health, including skin texture, smoothness, hydration, and skin tone evenness.

  • Walking is incredibly good for your skin. Weightlifting might be very bad for it. Intense cardio is risky as well. We recommend walking outdoors for 1-2 hours, every day. Although weightlifting and intense cardio offer health benefits, they are both proven to cause oxidative stress associated with acne. They also spike blood sugar/cortisol levels. This study concluded that “Although conflicting data exist, the preponderance of available information suggests that physical exercise promotes an increase in free-radical generation.” Walking helps manage blood sugar and reduce insulin levels and encourages spending more time outdoors, offering a holistic approach to skincare. According to this study, “regular walking is associated with lower levels of hemostatic and inflammatory markers independently of vigorous physical activity in healthy men and women.” This study provides evidence that practicing long-term regular continuous and intermittent walking may hold the potential for increasing antioxidant and decreasing lipid peroxidation, thus alleviating oxidative stress
  • Advising against weightlifting and intense cardio is the recommendation we are most hesitant about giving, and we don’t feel that strongly about it. However, there is a surprising amount of anecdotal feedback that weightlifting causes acne (see below). The studies cited above are conclusive that weightlifting and intense cardio increase oxidative stress, while walking reduces it. Based on these findings, we believe that replacing high-intensity exercise and weightlifting sessions with outdoor walking may lead to more favorable skin outcomes for individuals struggling with acne or rosacea.

  • Take lukewarm showers. Hot showers are inflammatory, irritating, dehydrating and cause histamine release.
  • Air filter: Buy a high-quality air filter. Particulates in the air are proven causes of inflammation. Use an air quality monitor to ensure that particulate counts in your home stay close to zero. This study concluded that air pollution is simultaneously associated with inflammation, oxidative stress, blood coagulation, and autonomic dysfunction in healthy young humans.

  • Eat earlier in the day, in sunlight if possible. Eating later in the day and at night doubles the thing of time your blood sugar stays elevated after a meal.

  • Raise your HDL, lower your LDL and Triglycerides. This study shows that dyslipidemia (high cholesterol) is common in acne patients, and that acne patients had lower HDL, higher Triglycerides, and lower LDL than healthy controls.

  • Wear a continuous glucose monitor to understand the glucose spikes that come from various meals and activities. The Dexcom G7 is the most accurate. The Freestyle Libre is a more affordable option. Keep your fasting blood glucose low and stable. Avoid meals that spike your blood sugar. You can get a CGM via SigNos.com. In just two weeks of wearing a CGM you’ll learn an incredible amount about your own health.
  • Improve your insulin sensitivity or lower your insulin resistance. Fasting and low-sugar diets can do this. In this controlled study, those with insulin resistance had significantly worse acne.
  • Meditation and stress avoidance. Develop an awareness of when you experience stress and take proactive steps to manage it. Incorporating daily meditation into your routine can help reduce stress levels and promote relaxation. Consider using a continuous glucose monitor (CGM) to track your blood sugar levels, as it can provide insights into your body’s stress response. When cortisol, the primary stress hormone, rises, it can cause a corresponding increase in blood sugar. Elevated cortisol and blood sugar levels have been linked to the development and exacerbation of acne, as well as other health issues. By effectively managing stress through techniques like meditation, mindfulness, and lifestyle modifications, you may see improvements in your skin health, sleep quality, and overall well-being. A 2017 study published in the journal Clinical, Cosmetic and Investigational Dermatology found that psychological stress can exacerbate acne severity. The study suggests that stress-induced hormones, such as cortisol and adrenal androgens, can increase sebum production and inflammation, contributing to acne development.
  • Avoid heavy metals. In this study of women, acne sufferers had significantly higher blood levels of lead and copper. Common sources of lead include cosmetics, high-mercury fish, unfiltered and contaminated tap water, and old paint. Regularly washing your hands, especially before eating, can help reduce the risk of ingesting heavy metals from contaminated surfaces. Some fast fashion retailers have been caught using lead in their clothing.
  • Avoid seed oils (also found in diet section). This study (chart below) found that individuals with acne have significantly higher levels of linoleic acid in their blood. The major dietary sources of linoleic acid are vegetable oils, nuts, seeds, meats, and egg. The study also showed that individuals with acne have significantly lower levels of six essential amino acids. If you are eating too little protein, this could be a factor in your skin problems.

Note the higher DHEA, lineloic acid, IL Cytokines, and lower essential amino acids among acne sufferers in the chart below

  • Another study showing that Insulin and Insulin resistance (HOMA) are much higher in patients with acne. Best ways to improve insulin resistance: Fasting, a low glycemic load diet, exerising after eating, regular weightlifting. Losing excess body fat, particularly visceral fat around the abdominal area, can significantly improve insulin sensitivity. High insulin is responsible for increased proliferation and dysfunction of keratinocytes by stimulation of IGF-1 receptors. Hypersecretion of IGF-1 leads to abnormal sebum production. Extended fasting is proven to reduce IGF-1.

  • Get tested for H. Pylori. This study showed a strong link between H. Pylori and acne.

  • Blood tests Ask your doctor for a blood test of inflammation markers (C-reactive protein, TNF-A, IL-6,IL-8), insulin resistance, white blood cells, neutrophils, fibrinogen, platelet count, ferretin, fibrinogen), fasting glucose, fasting insulin, hba1c, cholesterol, triglycerides, DHEA, DHT, SHBG, testosterone, estrogen, progesterone, zinc, vitamin Bs, vitamin D, AST, ALT, Erythrocyte Sedimentation Rate (ESR) and other standard biomarkers.
  • Test your home for mold. Mold is a common cause of many types of skin problems.

Food sensitivity tests you may want to explore.

  • Mediator Release Test (MRT): This blood test measures the reaction of white blood cells to different foods and chemicals, which might indicate food sensitivities.
  • Hydrogen Breath Test: Often used to diagnose lactose intolerance and other carbohydrate sensitivities, this test measures the amount of hydrogen in your breath after consuming a suspect food. High levels of hydrogen can indicate a digestion problem related to the food.
  • Skin Prick Test (SPT): This involves placing a small amount of the suspected allergen on the skin, usually on the forearm, and then gently pricking the skin so the allergen goes under the surface. If you’re allergic, a small, raised bump (similar to a mosquito bite) will appear.
  • Blood Test (Specific IgE): This test measures the level of IgE antibodies to specific foods in your blood. High levels of IgE antibodies for a particular food can indicate an allergy to that food.
  • Cordain’s Hunter Gatherer Tribe Studies: This remarkable study in which 1200 Kitavan (hunter gatherers in Papua New Guinea) and 115 Ache (hunter gatherers in Paraguray) subjects were examined (including 315 aged 15-25 years), there were zero cases of acne. The astonishing difference in acne incidence rates between non-westernized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing lifestyle factors. Tubers, fruit, fish, and coconut represent the dietary mainstays in Kitava. Dietary habits are virtually uninfluenced by Western foods in most households. The intake of dairy products, alcohol, coffee, and tea was close to nil, and that of oils, margarine, cereals, sugar, and salt was negligible. Estimated carbohydrate intake was high, almost 70% of daily energy, while total fat intake was low (20% of daily energy). Virtually all of the dietary carbohydrate intake was in the form of low–glycemic load tubers, fruits, and vegetables.
  • Wear 100% cotton clothing, especially your underwear. Always wash clothes with an extra rinse cycle to keep detergents and chemicals off of your clothing.
  • Don’t drink out of plastic containers or aluminum cans (which all have plastic lining) or eat using plastic silverware. Don’t touch receipts. Drink out of glass bottles. If you cannot afford that, use a high-quality filter for tap water. Microplastics are endocrine (hormone) disruptors, and hormone disruption is a factor in acne.
  • Ramp down mTor. Acne is an mTORC1 (mammalian target of rapamycin))-driven anabolic and inflammatory skin disease. Therefore, we should use all mechanisms at our disposal to ramp down mTOR.  Ways to ramp down mTOR include fasting, protein (Lucerne in particular) restriction, eating less meat, and exercising. Supplements such as berberine, Quercetin, EGCG, and spermidine lower mTOR, as do foods such as Black Cumin, Vinegar, and Hibiscus. Use a high-quality filter on your shower and sink. Letting fluoride, chlorine, and other chemicals in tap water touch your skin can cause irritation.

More resources for good health and good skin:

  • Breath book by James Nestor. Improve your breathing to improve your health
  • Bryan Mirabella’s instagram. He’s a breath coach. Great breathing will change your life.
  • Article written by “Databased” on sunlight, zinc, superoxide dismutase, and acne.

Studies referenced in this post

  • Acne vulgaris: a disease of Western civilization – Loren Cordain – 2002 – “Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed.” Tubers, fruit, fish, and coconut represent the dietary mainstays in Kitava. Dietary habits are virtually uninfluenced by Western foods in most households. The intake of dairy products, alcohol, coffee, and tea was close to nil, and that of oils, margarine, cereals, sugar, and salt was negligible. Estimated carbohydrate intake was high, almost 70% of daily energy, while total fat intake was low (20% of daily energy). Virtually all of the dietary carbohydrate intake was in the form of low–glycemic load tubers, fruits, and vegetables

  • The Relationship Between Acne Vulgaris and Insulin Resistance – Hasrat and Al-Yassen – “The results found that 81% and 67% of acne patients have insulin resistance based on their C-peptide and TyG index levels”
  • Insulin resistance in severe acne vulgaris – Emioroglu, Cengiz, Kemeriz (2015) – “While fasting blood glucose levels were not different between the groups (p > 0.05, 82.91 ±9.76 vs. 80.26 ±8.33), the fasting insulin levels were significantly higher in the patient group than in the control group (p < 0.001, 14.01 ±11.94 vs. 9.12 ±3.53). Additionally, there was a highly significant difference between the patient and control groups in terms of HOMA values (p < 0.001, 2.87 ±2.56 vs. 1.63 ±0.65). These results suggest that insulin resistance may have a role in the pathogenesis of acne.”
  • Oxidative Stress in Patients With Acne Vulgaris – Arican, Kurutas, Sasmas (2005) – “CAT and G6PD levels in patients were found to be statistically decreased, and SOD and MDA levels were found to be statistically increased (P < .001). However, any statistical difference and correlation could not be found between the severity and distribution of lesions and the mean levels of enzymes. In addition, we found that each enzyme is correlated with one another. Our findings show that oxidative stress exists in the acne patients.”
  • Oxidative stress in acne vulgaris: an important therapeutic target – Sahib, Al-Anbari, Raghif (2013) – “The results of the serum level analysis of  MDA (malondialdehyde) for the acne patients (expressed as the mean standard deviation)  was highly significant  (P value  ≤  0.001) higher than that of healthy volunteers,  while serum level of  GSH (glutathione) was highly significant (P  value  ≤ 0.001)  lower in acne patients compared to healthy volunteers; there is a significant difference (P value ≤ 0.05) found in serum levels of IL-8 between the acne patients and the healthy volunteers. Conclusions: The results obtained in this study clearly showed the existence of oxidative stress in  patients with acne vulgaris and that oxidative stress, along with inflammation, play a critical role in acne  pathogenesis;  furthermore,  oxidative  stress  in  acne  patients  may represent a  potential therapeutic target and interference with antioxidant is a rationale choice”
  • Serum levels of hypersensitive-C-reactive protein in moderate and severe acne – Namazi – This study found differences in CRP between severe and moderate acne cases, but not between case and control.
  • Evaluation of Serum Levels of Interleukins 6, 8, 17 and 22 in Acne Vulgaris: A Cross-Sectional – Singh, Khurana, Chitkara (2023) – “IL-8 and IL-17 play a critical effector role in the pathogenesis of Acne”
  • Association of TNF-α polymorphisms (−857, −863 and −1031), TNF-α serum level and lipid profile with acne vulgaris – 2021 – “Importantly, TNF-α (Tumor necrosis factor is an adipokine and a cytokine) serum level was significantly increased in acne patients with severe disease symptoms. Furthermore, levels of total cholesterol (TC) and triglycerides (TG) were significantly increased, whereas high-density lipoprotein cholesterol (HDL-C) level was significantly decreased in acne patients”
  • A Novel Inflammatory Marker in the Follow-up of Moderate-to-Severe Acne Vulgaris Administered Isotretinoin: Systemic Immune-Inflammation Index (SII) Turan (2022). patients with moderate-to-severe acne vulgaris had significantly higher neutrophil counts, platelets, and SII levels than healthy controls. Isotretinoin (acutane) improved inflammation markers.

  • Acne Severity and Sleep Quality in Adults – Schrom (2022) – When controlling for DLQI and PHQ-2, the average subjective sleep score decreased (i.e., worsened) as the objective acne severity score (GAGS) increased and vice versa (p = 0.0306, parameter estimate = −0.09003). In 2015, a French study demonstrated that there is a strong positive correlation between acne and fatigue upon waking (i.e., poor sleep quality) even when adjusting for age (p < 0.0001). It also demonstrated stressed patients have greater fatigue upon waking (p < 0.0001) and are more likely to have acne.
  • Strategies for Reducing or Preventing the Generation of Oxidative Stress – Poljsak (2011) – “A growing body of evidence supports the hypothesis that CR, with no malnutrition and an adequate mineral intake, also works by decreasing oxidative stress”. “A person should thus practice regular, but moderate physical activity.” “Glucose in the blood increases after consuming a meal, and for this reason, work instead of resting should be performed in order to maintain an appropriate electron flow and avoid electron leaks.”
  • Evaluation of Hormonal Factors in Acne Vulgaris and the Course of Acne Vulgaris Treatment with Contraceptive-Based Therapies in Young Adult Women – Dominika Borzyszkowska (2022) – This study of women found a strong correlation between testosterone, androstendione, cortisol, and acne. The study also found that oral contraceptives alone and also combined with Cyproterone Acetate and Isotretinoin improved acne. “Androgenic stimulation of the sebaceous glands is an important factor in the development of acne”. “However, in a contradictory study, the authors found no positive correlation between acne severity and any of the clinical or laboratory markers of androgenization that were assessed. On the contrary, these authors found lower free testosterone index values and higher SHBG levels in women with higher acne severity. These results suggested that the severity of acne symptoms in adult women is not determined by androgen production.”
  • Sebum analysis of individuals with and without acne. “The subjects with acne had more sebum (59%) than the control subjects. The lipid that differed the most between the two groups was Squalene, which was upregulated in acne sebum by a 2.2-fold. The only class of lipids that was reduced in the sebum of acne subjects was the free fatty acids, which were suppressed more than 20%. However, this result did not demonstrate statistical significance.” Squalene is a precursor of cholesterol.
  • Effects of Long-Term Regular Continuous and Intermittent Walking on Oxidative Stress, Metabolic Profile, Heart Rate Variability, and Blood Pressure in Older Adults with Hypertension. “Extremely study on walking.”This study provides evidence that practicing long-term regular continuous and intermittent walking may hold the potential for increasing antioxidant and decreasing lipid peroxidation, thus alleviating oxidative stress in older participants with hypertension. Moreover, the participants practicing continuous walking exhibited greater improvement in metabolic profile, while the participants practicing intermittent walking showed greater improvement in cardiac autonomic function.” “In bot groups, blood total GSH (p=0.023 and p ≤ 0.001) and GSH (p=0.022 and p ≤ 0.001) concentrations and the GSH/GSSG ratio (p=0.014 and p=0.002) increased significantly, and blood GSSG (p ≤ 0.001 and p=0.002) and plasma MDA (p=0.023 and p ≤ 0.001) concentrations decreased significantly following the 12-week exercise program”. Note that GSH and other markers here are strongly correlated with acne.

  • Insulin resistance in severe acne vulgaris – While fasting blood glucose levels were not different between the groups, the fasting insulin levels were significantly higher in the acne group than in the control group. Additionally, there was a highly significant difference between the patient and control groups in terms of HOMA (Homeostatic Model Assessment for Insulin Resistance) 
  • Insulin resistance in the course of acne – literature review – Anna Sadowska-Przytocka, Michalina Gruszczyńska, Anna Ostałowska, Patrycja Antosik, Magdalena Czarnecka-Operacz, Zygmunt Adamski, and Katarzyna Łącka. “Metformin seems to be an effective and interesting therapeutic modality for patients with acne. Treatment with metformin not only reduces GAGS value, stabilisation of the lipid profile, as well as serum glucose and insulin levels have also been recorded.” “Increased mTORC1 (mammalian target of rapamycin complex 1) signalling observed in both conditions mentioned above, seems to be an important factor and perhaps should be considered in the complex structure of treatment strategy in patients suffering from acne.” “Insulin Resistance might be a possible causative factor of resistance to a standard acne therapy in our clinical practice”
  • Dietary intervention in acne – Melnik (2012) – “Vegetable-accentuated diets provide less mTORC1 activating signals and additionally contain natural plant-derived mTORC1-inhibitors like resveratrol, EGCG, curcumin, genestein, and indole-3-carbinol monomers, precursors of 3,3′-diindolylmethane.” “All three major stimulatory pathways of mTORC1 activation have to be attenuated. Dietary intervention in acne should thus (1) decrease total energy, glucose and fat intake, (2) diminish insulin/IGF-1 signaling predominantly mediated by high dairy protein consumption, and (3) should limit the total leucine uptake predominantly provided by increased animal protein intake including meat and dairy proteins. This comprehensive dietary strategy can only be achieved by higher consumption of vegetables and fruit and reduction of animal-derived food. Indeed, diets enriched in vegetables and fruits, vegan diet as wells as Paleolithic diet (excluding sugar, hyperglycemic grains and dairy) have all been demonstrated to improve insulin sensitivity in type 2 diabetes, and metabolic syndrome and showed preventive effects in the development of Alzheimer disease. According to the recent Korean acne diet study, the frequency of vegetables and fish intake was significantly higher in the acne-free control group than in the acne group consuming more hyperglycemic carbohydrates, processed meat and dairy products.”
  • Turning acne on/off via mTORC1 – Danby (2013) – The short story of the Western diet is that highly refined carbohydrates like white flour are easily converted to simple sugars. This diet also contains a generally increased sugar load and these influences combine to support a chronically increased plasma glucose level. The result is a low-grade hyperinsulinemia that, through a phosphorylation process, persuades the transcription factor FoxO1 to leave the cell nucleus, exposing the androgen receptor to circulating androgens