Leptin Resistance Protocol; obesity, gut dysbiosis, hyperinflammation. Supplement examples included, link to Fullscript for more info about them.

The much longer text and reference sections are in a document.

Jan 16, 2023

Leptin regulates appetite and helps maintain weight normally, but elevated levels of leptin and resistance to it by the leptin receptors are associated with obesity along with having too few leptin receptors. (Iikuni, et al, 2008) It is inflammatory and adds to mast cell degranulation. Increased mast cell degranulation might cause increased histamine levels and sensitivities. Reducing histamine in the diet may be a need. Other anti-inflammatory tactics to control the leptin induced inflammation would also be a need and to protect mitochondria from oxidative stress. Leptin is made by adipose and other tissues. Overweight people would naturally be making more leptin and it may increase during inflammation from the other tissue types.

Leptin receptors may be co-regulated by bitter taste receptors or calcium channels. Both need zinc for gene transcription or the taste receptors and ion channels aren’t produced by the body.

A healthy microbiome may be critical for restoring leptin metabolism. Zinc and polyphenols also promote beneficial microbiome species. Zinc and resistant starch and fiber may be needed to reduce leptin resistance along with bitter tasting plant phytonutrients such as polyphenols from citrus or pomegranate peel and pulp.

A diet too high in calories from fats in ratio to protein and carbohydrate may add to leptin resistance and also lead to gut dysbiosis. A diet too high in saturated fats can lead to mitochondrial fermentation instead of the more efficient and less waste producing Citric Acid Cycle oxidation.

Here is the document with more of the science that supports the following recommendations, (Leptin Resistance Protocol pdf *1/21/2023, has the full Reference List now - it contains a lot more information than the summary here.)

Leptin Resistance Protocol summary points.

A high fat diet and lack of zinc and bitter phytonutrients may be involved in elevated leptin levels; negative effects on the microbiome from lack of zinc and reduced gene transcription of bitter taste receptors or other calcium channels may be additive factors.
Leptin is produced in so many tissue types that excess may be an underlying link to kidney, liver, and brain damage seen with histamine and Retinoid excess as leptin also degranulates mast cells. Inflammation is additive and can lead to allergy and pain sensitivity, migraines, and mood symptoms.
Goal – moderate excess leptin, increase leptin receptor activity, improve microbiome health, provide adequate zinc, magnesium, and bitter phytonutrients, resistant starches, and fiber rich foods.
Probiotic supplements or fermented foods may be helpful, although if histamine excess is a problem, go with the supplements and avoid fermented foods. Eat fiber rich foods and zinc and the beneficial species may grow naturally.
Decrease processed and ultra-processed foods and omega 6 vegetable oils, as they are associated with increased weight, leptin and inflammation, and increase omega 3 fatty acids. Keep saturated fat intake under 10% of the total calories and total fat under 50% of total calories.

What may help:

Zinc, magnesium, resistant starch and fiber in the diet. Mediterranean diet may help, with olive oil as a beneficial against leptin resistance. Mitochondrial support nutrients and niacin are likely to be helpful for microbiome species and mitochondria. Niacin treatment reduced leptin levels in a hypercholesterolemia animal model. (Yang, J. et al, 2008) Niacin (Si, et al, 2014, Wei, et al, 2014) and butyrate (Chen G, 2018) can down-regulate the inflammatory NF-κB signaling pathway, by activation of the GP109 receptor in mitochondria or coincident to TRP channels. (Zhou and Greka, 2016) Less NF-kB reduces mast cell degranulation and promotes more anti-inflammatory Nrf2.
A moderate 30% of calories from carbohydrate, 45-50% from fat with some saturated fats from coconut oil/products, and 20-25% from protein is the plan I approximately follow (with a vegan diet for autoimmune or Retinoid Toxicity reasons). Improve omega 3 to omega 6 ratio with the choice of oils that are used and supplement EPA/DHA if fatty fish aren’t used for protein sources a few times a week. Using lean meats/fish or beans are helpful to reduce the saturated fat percentage in the diet.
Bitter tasting citrus peel (just mince and use on food as a seasoning for example) and pomegranate peel or products, other bitter herbs, spices, foods (greens, leeks, ginger, horseradish for example, if tolerated), and rhubarb may be particularly beneficial.
Limit ultra-processed food as it is associated with increased leptin. (Fernandes, et al., 2023)
Limit/swap refined white flour and white sugar products with whole grains/ cooked and chilled for resistant starch or tapioca starch thickened pudding or fruit pie filling (more resistant starch content than corn starch, mix in part with garbanzo bean flour to increase protein and reduce the elasticity of the cooked tapioca – it is very resistant.) Use minced or pureed dates for sweetener with more fiber, pure maple syrup for sweetener with magnesium, manganese and other trace nutrients, or raw honey for anti-cancer benefits. Stevia in moderation is an herbal very low/zero calorie sweetener. Reducing the sweetness in foods slowly, can readjust the taste to prefer the less intense sweetness.
Water – have plenty – exercise – gentle full range motion, increase intensity at a safe and gradual pace over weeks.

Supplement examples:

More information about these supplements is viewable on Fullscript, register as a client of mine and you can order them or anything else in the catalog at 20% off. (us.fullscript.com/Leptin Resistance Protocol)

Citrus and pomegranate – polyphenols and antioxidant support (pick one, or use fresh fruit peel and save money):

AMPK Metabolic Activator - Life Extension - may help with weight loss - and the 500 mg hesperidin (a citrus bioflavonoid) may also help as a bitter phytonutrient. (1/day) Tablet *large tablets if that matters - I started using this product recently and it seems helpful. Due to histamine sensitivity I avoid citrus products now but can tolerate the purified hesperidin.

Citrus Bioflavonoids - NOW Foods - 700 mg citrus bioflavonoids, 50 mg rutin, and 50 mg vitamin C per ***gelatin capsule. It says NON-GMO though. I am not sure if there is such a thing as 'Non-GMO cow gelatin'. They may simply mean none of the ingredients are GMO crops. Citrus bioflavonoids can be purchased inexpensively as a bulk powder from places online like PureBulk. Then mix some in a beverage or salad or soup - less cost, less gelatin.

Pomegranate w/ Super Fruits - Progressive Labs - on vegetable capsule provides 400 mg Pomella TM extract and acai and mangosteen fruit extracts - antioxidant rich and microbiome support. Take once or twice a day, am and pm. May also help mood.

Probiotics that may support improved leptin response (pick one):

Aloe 10,000 & Probiotics - NOW Foods - Contains Bifidobacterium longum, see the next description. This probiotic has other strains and also contains aloe vera gel concentrate which has beneficial fiber and an anti-inflammatory phytonutrients that may help with insulin resistance and weight. (Yazdani, Hossini, Edalatmanesh, 2022) Vegan/vegetarian capsule.

Smidge® Sensitive Probiotic - Smidge - contains Bifidobacterium longum and Lactobacillus gasseri, two strains found helpful for effects on gene transcription of leptin and the leptin receptor. (Alard, et al., 2021) This supplement has other strains too and is designed for a more sensitive gut, SIBO, autism, and other conditions. See the product description. Methylcellulose capsule.

One-a-day methyl B’s powder supplement with some citrus bioflavonoids:

VitaSpectrum® Powder (Berry-Pomegranate) - Klaire Labs - this is a powder methyl B one a day mix with berry-pomegranate juice as flavoring. It has some citrus bioflavonoids too. It could be used for children or adults. The directions say to use the same dose for age 4 to adult - I would suggest weight estimates - small child 1/4 dose, medium child 1/2 dose, adolescent, 3/4 dose, teens, same dose as adults. The trace mineral and nutrient ratios look good. *Contains 150 mcg iodine, the basic guideline which may be too much for hyperthyroidism but too little for the average modern consumer.

Trace Mineral Complex – take with a Methyl B complex instead of a one-a-day if you need to avoid any of the nutrients in a one-a-day. See following section.

Trace Minerals Complex - Seeking Health - contains ten essential trace minerals in good ratios including 30 mg zinc, 2 mg copper, 4 mg manganese, 200 mcg selenium and chromium. Boron is low at only 500 mg (3 mg/day may be helpful) and iodine, at 250 mcg, is too much for someone with hyperthyroidism and only slightly more than the recommendation which is too low in a climate of fluoride and bromide. It is a good mix though. Vegetarian/vegan capsule.

Why a methyl One-A-Day?

Mitochondrial support needs a range of nutrients, most of them that we need too - making a good one-a-day complex helpful. Methyl forms of folate and B12 can save the body time for anyone or would be the active form for people who are ill in part because of methylation difficulties.

Switch the mindset that overweight is excess food and think of overweight as excess inflammation and lack of key nutrients. Anytime we are inflamed we need extra vitamin C, antioxidants, magnesium, and all the B vitamins. Niacin and butyrate in particular help the body to remove excess inflammation. Oxidative stress adds to leptin issues and flavonoids can help or other antioxidants by reducing the oxidative chemicals.

Who shouldn't take a one-a-day supplement?

Some people may need to avoid vitamin A and carotenoids due to Retinoid Toxicity (ME/CFS potentially, vaccine injured, and LongCovid possibly) ask for more information especially if skin rash is a symptom. Some people may need to avoid vitamin D - sarcoidosis, cancer of the parathyroid gland and certain infections. People with hyperthyroidism have to avoid iodine. Do not add mixes as some trace minerals can also reach toxicity quickly. Use the Trace Mineral mix with a Methyl B complex and a vitamin D3 - there is most of a one-a-day without the iodine and vitamin A which I can't have as an example person who does better without a one-a-day supplement.

I mince the inner pomegranate peel and use fresh or frozen in foods and I use the outer rind fresh or dried in a long steep tea which I may use in cooking or as a beverage. (bring to boil, simmer or remove from heat, leave covered for 20-30 minutes - more of an extract than a black tea that is steeped for a couple minutes.

Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.